Model based on adriamycin induced multi-organ injury and detection method

By conducting staged monitoring of animal models, we can judge the degree of organ damage to doxorubicin, which solves the problems of cumbersome and high cost in the existing technology, and realizes a simple and effective detection method.

CN119395310AInactive Publication Date: 2025-02-07KCI BIOTECH(SUZHOU) INC
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Patent Information

Application Number
CN202411511054.4
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-10-28
Publication Date
2025-02-07
Estimated Expiration
Not applicable · inactive patent

AI Technical Summary

Technical Problem

At this stage, the evaluation method for doxorubicin on the degree of organ damage is complicated, requiring multiple animal models, and the detection process is complex and costly.

Method used

Provide a detection method based on doxorubicin-induced multi-organ damage. By performing staged monitoring of body weight, blood samples, cardiac ultrasound, heart, liver and kidney weight and pathological sections on animal models, summarize and analyze monitoring information to Determine the degree of organ damage to doxorubicin.

Benefits of technology

The detection method is simplified, and only one animal model needs to be monitored in three stages. The detection method is simple and effective, and the detection cost is low.

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Abstract

The invention discloses a model and detection method based on adriamycin-induced multi-organ injury, and the method comprises the steps: selecting an animal model for detection, carrying out the first-stage index monitoring of the animal model, including the monitoring of the weight, blood sample and heart B ultrasound of the animal model, and recording the monitoring information; preparing a doxorubicin solution, and injecting the doxorubicin solution into the animal model body through an intravenous injection; second-stage index monitoring is carried out on the animal model, wherein the second-stage index monitoring comprises the steps of monitoring the weight, blood samples and heart B ultrasound of the animal model and recording monitoring information; performing third-stage index monitoring on the animal model, namely monitoring the weights and pathological sections of the heart, the liver and the kidney of the animal model and recording monitoring information; monitoring information recorded in the first-stage index monitoring, the second-stage index monitoring and the third-stage index monitoring is summarized and analyzed, and the damage degree of adriamycin to organs is judged.
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Description

Technical Field

[0001] The present application relates to the technical field of drug detection models, and in particular to a model and detection method based on doxorubicin-induced multi-organ damage. Background Art

[0002] Doxorubicin is an anthracycline anti-tumor drug commonly used in clinical practice, and is usually used to treat many types of cancer. However, it has side effects, including vomiting, rash, hair loss and bone marrow suppression. The most dangerous side effects are cardiomyopathy, myocardial fibrosis and heart failure. At the same time, it can have direct toxic effects on the glomerular and tubular epithelium, causing damage to the membrane barrier and absorption function of the proximal tubular epithelial cells of the kidney and disintegration of the cell nucleus. The detached tubular epithelial cells form casts with the proteins and other cellular components in the tubular lumen, blocking the tubular lumen, leading to increased intratubular pressure, aggravating kidney damage, and ultimately leading to chronic renal failure.

[0003] At present, the evaluation methods for the degree of organ damage caused by doxorubicin are relatively cumbersome, requiring the use of multiple animal models, and the detection process is complicated and the detection cost is high. Summary of the invention

[0004] In order to overcome the above shortcomings, the purpose of the present application is to provide a model and detection method based on doxorubicin-induced multi-organ damage, thereby effectively solving the above technical problems.

[0005] In order to achieve the above objectives, this application adopts the following technical solutions:

[0006] In a first aspect, the present application provides a method for detecting multiple organ damage induced by doxorubicin, comprising the following steps:

[0007] Selecting an animal model for detection, and performing first-stage indicator monitoring on the animal model, wherein the first-stage indicator monitoring includes: monitoring the weight, blood sample, and cardiac B-ultrasound of the animal model and recording the monitoring information;

[0008] preparing an adriamycin solution, and injecting the adriamycin solution into an animal model via intravenous injection;

[0009] Performing second-stage index monitoring on the animal model, the second-stage index monitoring comprising: monitoring the weight, blood sample and cardiac B-ultrasound of the animal model and recording the monitoring information;

[0010] Performing third-stage index monitoring on the animal model, wherein the third-stage index monitoring includes: monitoring the weight and pathological sections of the heart, liver and kidney of the animal model and recording the monitoring information;

[0011] The monitoring information recorded in the first stage indicator monitoring, the second stage indicator monitoring and the third stage indicator monitoring are respectively summarized and analyzed to determine the degree of organ damage caused by doxorubicin.

[0012] Furthermore, the first stage indicator monitoring is before the animal model is injected with doxorubicin solution, the second stage indicator monitoring is at the 2nd week, 3rd week, 4th week, 5th week, 6th week and 7th week after the animal model is injected with doxorubicin solution, and the third stage indicator monitoring is at the 8th week after the animal model is injected with doxorubicin solution.

[0013] Furthermore, in the first-stage indicator monitoring and the second-stage indicator monitoring, monitoring the blood sample of the animal model includes:

[0014] 1 mL of blood was drawn from the vein of the animal model and allowed to stand for 30 minutes, and the serum in the blood was analyzed at 4°C. The serum was tested to obtain the index parameters of serum creatinine, urea nitrogen, troponin I, alanine aminotransferase, aspartate aminotransferase, total bilirubin, glutamyl transferase, and alkaline phosphatase in the blood sample.

[0015] Furthermore, in the first-stage indicator monitoring and the second-stage indicator monitoring, the cardiac B-ultrasound monitoring of the animal model includes:

[0016] The left ventricular ejection fraction, left ventricular shortening fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume of the animal model were detected by an ultrasonic detector.

[0017] Furthermore, before monitoring the third stage indicators of the animal model, the heart, liver and kidney of the animal model are first obtained, which includes:

[0018] Eight weeks after the animal model was injected with doxorubicin solution, the animal model was anesthetized with isoflurane, the abdominal cavity of the animal model was opened along the midline of the abdomen, the chest cavity was opened along the diaphragm and the sternal costal cartilage, the inferior vena cava was cut off, and physiological saline was perfused through the abdominal aorta. The heart, liver and kidney were removed after the blood stains on the heart, liver and kidney faded.

[0019] Furthermore, in the third stage indicator monitoring, monitoring the weight of the heart, liver and kidney of the animal model includes:

[0020] The heart, liver and kidney were weighed, the ratio of the organ weight to the body weight of the animal model was calculated, and after weighing, the heart, liver and kidney were immersed in 10% formalin for preservation.

[0021] Furthermore, in the third stage indicator monitoring, monitoring of the pathological sections of the heart, liver and kidney of the animal model includes:

[0022] Monitoring of pathological sections of the heart, liver and kidneys of the animal model includes:

[0023] Paraffin tissue sections were made from the heart, liver, and kidneys immersed in 10% formalin, and the pathological sections were stained and scanned panoramically using a section scanner. The thickness of the cardiac ventricular wall of the stained pathological sections was measured, the percentage of cardiac fibrosis area was scanned, the injury scores of hepatocyte degeneration, hepatocyte necrosis, and liver inflammatory cell infiltration were measured, the percentage of liver fibrosis area was scanned, the changes in kidney damage were analyzed, and the percentage of kidney fibrosis area was scanned.

[0024] Further, staining the pathological sections includes hematoxylin and eosin staining, and under the hematoxylin and eosin staining:

[0025] The cardiac ventricular wall thickness, hepatocyte degeneration, hepatocyte necrosis, liver inflammatory cell infiltration injury score and kidney injury changes were measured in the stained pathological sections.

[0026] Staining of pathological sections includes Masson's staining, under which:

[0027] The scanned areas included the percentage of cardiac fibrosis, the percentage of liver fibrosis, and the percentage of kidney fibrosis.

[0028] Furthermore, the preparation of the doxorubicin solution comprises:

[0029] Take doxorubicin powder, add physiological saline, and mix the doxorubicin powder and the physiological saline by vortexing and ultrasonication until there are no particles visible to the naked eye in the solution. The concentration of the doxorubicin solution is 1 mg / mL.

[0030] In a second aspect, the present application also provides a model of multiple organ damage induced by doxorubicin, which is used in any of the detection methods for multiple organ damage induced by doxorubicin.

[0031] Beneficial Effects

[0032] The present application provides a detection method based on doxorubicin-induced multi-organ damage. In this method, only one animal model is needed to monitor the model's body weight, blood samples, cardiac B-ultrasound, heart, liver and kidney weights, and pathological sample sections in three stages. The detection method is simple and effective, and the detection cost is low. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] The accompanying drawings are used to provide an understanding of the technical solution of the present disclosure and constitute a part of the specification. Together with the embodiments of the present disclosure, they are used to explain the technical solution of the present disclosure and do not constitute a limitation on the technical solution of the present disclosure. The shapes and sizes of the components in the accompanying drawings do not reflect the actual proportions and are only intended to illustrate the content of the present application.

[0034] Figure 1 This is a flow chart of the detection method of this application.

[0035] Figure 2 This is a kidney injury scoring standard diagram in one embodiment of the present application.

[0036] Figure 3 This is a liver injury scoring standard diagram in one embodiment of the present application.

[0037] Figure 4 This is a graph showing the weight change of a model in one embodiment of the present application.

[0038] Figure 5 This is a diagram showing changes in serum troponin I in a model in one embodiment of the present application.

[0039] Figure 6 This is a diagram showing changes in serum alanine aminotransferase in a model in one embodiment of the present application.

[0040] Figure 7 This is a diagram of the changes in serum aspartate aminotransferase of a model in one embodiment of the present application.

[0041] Figure 8 This is a diagram showing changes in serum alkaline phosphatase in a model according to an embodiment of the present application.

[0042] Fig. 9 This is a model serum creatinine change diagram in one embodiment of the present application.

[0043] Fig.10 This is a diagram showing changes in model serum urea nitrogen in one embodiment of the present application.

[0044] Fig.11 This is a diagram showing changes in the model left ventricular ejection fraction in one embodiment of the present application.

[0045] Fig.12 This is a graph showing changes in the model left ventricular shortening fraction in one embodiment of the present application.

[0046] Fig.13 This is a diagram of the change in the end-diastolic volume of the model left ventricle in one embodiment of the present application.

[0047] Fig.14 This is a diagram of the change in the end-diastolic volume of the model right ventricle in one embodiment of the present application.

[0048] Fig.15This is a diagram showing changes in the heart weight and the ratio of heart weight to body weight of a model in one embodiment of the present application.

[0049] Fig.16 This is a graph showing the ratio changes of the model's liver weight, heart weight and body weight in one embodiment of the present application. Fig.17 This is a graph showing the ratio of kidney weight, heart weight and body weight in an embodiment of the present application.

[0050] Fig.18 This is a horizontal staining image of the papillary muscles of a coronary section of the heart in one embodiment of the present application.

[0051] Fig.19 This is a diagram showing changes in left ventricular wall thickness in one embodiment of the present application.

[0052] Fig. 20 This is a diagram showing changes in interventricular septum thickness in one embodiment of the present application.

[0053] Fig.21 This is a diagram showing changes in right ventricular wall thickness in one embodiment of the present application.

[0054] Fig. 22 This is a graph showing changes in myocardial injury score in one embodiment of the present application.

[0055] Fig.23 This is a diagram showing changes in myocardial fibrosis in one embodiment of the present application.

[0056] Fig.24 This is a staining image of the liver portal area in one embodiment of the present application.

[0057] Fig.25 This is a hepatocyte degeneration scoring diagram in one embodiment of the present application.

[0058] Fig.26 This is a liver cell necrosis scoring diagram in one embodiment of the present application.

[0059] Fig. 27 This is a liver inflammatory cell infiltration scoring diagram in one embodiment of the present application.

[0060] Fig.28 This is a graph showing the total liver injury score in one embodiment of the present application.

[0061] Fig.29 This is a liver fibrosis scoring diagram in one embodiment of the present application.

[0062] Fig.30 This is a kidney staining image in one embodiment of the present application.

[0063] Fig.31 This is a graph showing changes in kidney injury score in one embodiment of the present application.

[0064] Fig.32 This is a graph showing changes in the proportion of renal fibrosis in one embodiment of the present application. DETAILED DESCRIPTION

[0065] The above scheme is further described below in conjunction with specific examples. It should be understood that these examples are used to illustrate the present application and are not limited to the scope of the present application. The implementation conditions adopted in the examples can be further adjusted as the conditions of the specific manufacturer, and the unspecified implementation conditions are usually the conditions in conventional experiments.

[0066] Unless otherwise defined, the technical terms or scientific terms used in the embodiments of the present disclosure should be understood by people with ordinary skills in the field to which the present application belongs. The "first", "second" and similar words used in the embodiments of the present disclosure do not indicate any order, quantity or importance, but are only used to distinguish different components. "Including" or "comprising" and similar words mean that the elements or objects appearing in front of the word include the elements or objects listed after the word and their equivalents, without excluding other elements or objects. "Connecting" or "connected" and similar words are not limited to physical or mechanical connections, but can include electrical connections, whether direct or indirect. In this article, "electrical connection" includes the situation where the constituent elements are connected together through an element with some electrical function. "Elements with some electrical function" are not particularly limited as long as they can transfer electrical signals between the connected constituent elements. "Elements with some electrical function" can be, for example, electrodes or wiring, or switching elements such as transistors, or other functional elements such as resistors, inductors or capacitors. "Up", "down", "left", "right", etc. are only used to indicate relative position relationships. When the absolute position of the object being described changes, the relative position relationship may also change accordingly.

[0067] In this application, the directions or positional relationships indicated by the terms "upper", "lower", "inner", "middle", etc. are based on the directions or positional relationships shown in the drawings. These terms are mainly used to better describe the present application and its embodiments, and are not used to limit the indicated devices, elements or components to have a specific direction, or to be constructed and operated in a specific direction.

[0068] As described in the background technology, doxorubicin is an anthracycline antitumor drug commonly used in clinical practice, usually used to treat many types of cancer, but it has side effects, including vomiting, rash, hair loss and bone marrow suppression. The most dangerous side effects are cardiomyopathy, myocardial fibrosis and heart failure. At the same time, it can have direct toxic effects on the glomerular and tubular epithelium, causing damage to the membrane barrier and absorption function of the renal proximal tubular epithelial cells and cell nucleus disintegration; the detached tubular epithelial cells and the proteins and other cellular components in the tubular lumen form casts, blocking the tubular lumen, leading to increased intratubular pressure, aggravating kidney damage, and ultimately forming chronic renal failure; at this stage, the evaluation methods for the degree of organ damage caused by doxorubicin are relatively cumbersome, requiring the use of multiple animal models, and the detection process is complicated and the detection cost is high.

[0069] In view of the above content, the inventor provides a detection method based on doxorubicin-induced multi-organ damage, such as Figure 1 As shown, the method comprises the following steps:

[0070] S1. Select an animal model for detection, and perform first-stage indicator monitoring on the animal model. The first-stage indicator monitoring includes: monitoring the weight, blood sample, and cardiac B-ultrasound of the animal model and recording the monitoring information;

[0071] S2, preparing an adriamycin solution, and injecting the adriamycin solution into the animal model via intravenous injection;

[0072] S3, performing second-stage indicator monitoring on the animal model, the second-stage indicator monitoring comprising: monitoring the weight, blood sample and cardiac B-ultrasound of the animal model and recording the monitoring information;

[0073] S4, monitoring the third stage indicators of the animal model, wherein the third stage indicator monitoring includes: monitoring the weight and pathological sections of the heart, liver and kidney of the animal model and recording the monitoring information;

[0074] S5. Summarize and analyze the monitoring information recorded in the first stage indicator monitoring, the second stage indicator monitoring, and the third stage indicator monitoring to determine the degree of organ damage caused by doxorubicin.

[0075] The present application provides a method that only requires one animal model to monitor the model's body weight, blood samples, cardiac B-ultrasound, heart, liver and kidney weights, and pathological sample sections in three stages. The detection method is simple and effective, and the detection cost is low.

[0076] Next, combine Figure 2-Figure 32 As shown, the present application is described exemplarily.

[0077] An embodiment of the present application discloses a method for detecting multiple organ damage induced by doxorubicin, the method comprising:

[0078] The animal model used for testing was the New Zealand rabbit model.

[0079] Before injecting the adriamycin solution into the New Zealand rabbit model, the model was first monitored for the following indicators:

[0080] Weigh the model and monitor the model's weight;

[0081] 1 mL of blood was drawn from the model's ear vein and allowed to stand for 30 min. The serum in the blood was analyzed at 4°C. The serum was tested to obtain the index parameters of serum creatinine, urea nitrogen, troponin I, alanine aminotransferase, aspartate aminotransferase, total bilirubin, glutamyl transferase, and alkaline phosphatase in the blood sample.

[0082] The left ventricular ejection fraction, left ventricular shortening fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume of the animal model were detected by an ultrasonic detector.

[0083] Take doxorubicin powder, add physiological saline, mix the doxorubicin powder and the physiological saline by vortexing and ultrasonication until there are no particles visible to the naked eye in the solution, and prepare a doxorubicin solution with a concentration of 1 mg / mL.

[0084] The prepared doxorubicin solution (1 mg / mL) was injected into the ear vein of the model twice a week for 8 consecutive weeks.

[0085] The model was monitored for the second phase of indicators after the injection of doxorubicin solution:

[0086] Weigh the model again to monitor the model's weight;

[0087] 1 mL of blood was drawn from the model's ear vein and allowed to stand for 30 min. The serum in the blood was analyzed at 4°C. The serum was tested to obtain the index parameters of serum creatinine, urea nitrogen, troponin I, alanine aminotransferase, aspartate aminotransferase, total bilirubin, glutamyl transferase, and alkaline phosphatase in the blood sample.

[0088] The left ventricular ejection fraction, left ventricular shortening fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume of the animal model were detected by an ultrasonic detector.

[0089] Eight weeks after the injection of doxorubicin solution into the model, the animal model was anesthetized with isoflurane, the abdominal cavity of the animal model was opened along the midline of the abdomen, the chest cavity was opened along the diaphragm and the sternal costal cartilage, the inferior vena cava was cut off, and physiological saline was perfused through the abdominal aorta. After the blood stains on the heart, liver and kidneys faded, the heart, liver and kidneys were taken out.

[0090] After obtaining the model's heart, liver and kidney organs, the third stage of indicator monitoring was carried out:

[0091] The heart, liver and kidney were weighed, the ratio of the organ weight to the body weight of the animal model was calculated, and after weighing, the heart, liver and kidney were immersed in 10% formalin for preservation.

[0092] Paraffin tissue sections were made from the heart, liver, and kidney immersed in 10% formalin, and the pathological sections were stained, including H&E (hematoxylin-eosin) staining and MASSON (Masson) staining. The slices were panoramically scanned using a Hamamatsu Nano Zoomer Digital Pathology (S210) slice scanner, the thickness of the cardiac ventricular wall was measured under H&E staining, the percentage of cardiac fibrosis area was scanned under MASSON staining, the injury scores such as hepatocyte degeneration, hepatocyte necrosis, and liver inflammatory cell infiltration were measured under H&E staining, the percentage of liver fibrosis area was scanned under MASSON staining, the changes in kidney injury were analyzed under H&E staining, and the percentage of kidney fibrosis area was scanned under MASSON staining.

[0093] After obtaining the model monitoring parameters, combined with Figure 2-Figure 32 As shown in the figure: pre (before the model was injected with doxorubicin), D-corresponding number (the corresponding number of days after the model was injected with doxorubicin), Normal (before the model was injected with doxorubicin, i.e., the normal model), Model l-number wks (the corresponding number of weeks after the model was injected with doxorubicin)

[0094] The specific results are as follows:

[0095] Body weight changes: After doxorubicin injection, the body weight of the model animals decreased and the growth trend slowed down.

[0096] Changes in serum troponin I: 6 weeks after doxorubicin injection, serum troponin I was significantly increased compared with before injection.

[0097] Changes in serum aspartate aminotransferase: 7 weeks after doxorubicin injection, serum aspartate aminotransferase tended to increase compared with before injection.

[0098] Changes in serum alanine aminotransferase: 7 weeks after doxorubicin injection, serum alanine aminotransferase tended to increase compared with before injection.

[0099] Changes in serum alkaline phosphatase: As the doxorubicin injection cycle increased, serum alkaline phosphatase decreased significantly compared with before injection.

[0100] Changes in serum creatinine: After doxorubicin injection, serum creatinine tended to increase compared with before injection.

[0101] Changes in serum urea nitrogen: After doxorubicin injection, serum urea nitrogen tended to increase compared with before injection.

[0102] Changes in left ventricular ejection fraction: As the doxorubicin injection period increased, the left ventricular ejection fraction decreased significantly compared with before injection.

[0103] Changes in left ventricular fractional shortening: As the doxorubicin injection period increased, the left ventricular fractional shortening decreased significantly compared with before injection.

[0104] Changes in left ventricular end-diastolic volume: As the doxorubicin injection period increased, the left ventricular end-diastolic volume increased significantly compared with before injection.

[0105] Changes in left ventricular end-systolic volume: As the doxorubicin injection period increased, the left ventricular end-systolic volume increased significantly compared with before injection.

[0106] Heart weight / body weight changes: After doxorubicin injection, there was no significant change in heart weight / body weight in the model group compared with before injection.

[0107] Changes in liver weight / body weight: After doxorubicin injection, there was no significant change in liver weight / body weight in the model group compared with before injection.

[0108] Kidney weight / body weight changes: After doxorubicin injection, there was no significant change in kidney weight / body weight in the model group compared with before injection.

[0109] Changes in ventricular wall thickness: After doxorubicin injection, the left ventricular wall, right ventricular wall and ventricular septum in the model group were significantly thickened compared with before injection.

[0110] Changes in myocardial injury scores: After doxorubicin injection, the myocardial injury score in the model group was significantly increased compared with before injection.

[0111] Changes in myocardial fibrosis: After doxorubicin injection, the cardiac fibrosis area in the model group increased significantly compared with before injection.

[0112] Changes in liver injury scores: After doxorubicin injection, the degree of hepatocyte degeneration, hepatocyte necrosis and liver inflammatory cell infiltration in the model group was significantly increased compared with before injection.

[0113] Changes in liver fibrosis: After doxorubicin injection, the liver fibrosis area in the model group increased significantly compared with the group before injection.

[0114] Kidney injury score: After doxorubicin injection, the renal cortical injury score and renal medullary injury score in the model group were significantly increased compared with those before injection.

[0115] Changes in renal fibrosis: After doxorubicin injection, the renal fibrosis area in the model group increased significantly compared with before injection.

[0116] Another embodiment of the present application provides a model of multiple organ damage induced by doxorubicin, which is used in the detection method of multiple organ damage induced by doxorubicin in any of the above embodiments.

[0117] The above embodiments are only for illustrating the technical concept and features of the present application, and their purpose is to enable people familiar with the technology to understand the content of the present application and implement it accordingly, and they cannot be used to limit the protection scope of the present application. Any equivalent transformation or modification made according to the spirit of the present application shall be included in the protection scope of the present application.

Claims

1. A method for detecting multiple organ damage induced by doxorubicin, characterized in that: The steps include: Selecting an animal model for detection, and performing first-stage indicator monitoring on the animal model, wherein the first-stage indicator monitoring includes: monitoring the weight, blood sample, and cardiac B-ultrasound of the animal model and recording the monitoring information; preparing an adriamycin solution, and injecting the adriamycin solution into an animal model via intravenous injection; Performing second-stage index monitoring on the animal model, the second-stage index monitoring comprising: monitoring the weight, blood sample and cardiac B-ultrasound of the animal model and recording the monitoring information; The animal model is subjected to the third stage indicator monitoring, and the third stage indicator monitoring includes: Monitoring the weight and pathological sections of the heart, liver and kidney of the animal model and recording the monitoring information; The monitoring information recorded in the first stage indicator monitoring, the second stage indicator monitoring and the third stage indicator monitoring are respectively summarized and analyzed to determine the degree of organ damage caused by doxorubicin.

2. The detection method based on doxorubicin-induced multiple organ damage according to claim 1, characterized in that: The first stage indicator monitoring is before the animal model is injected with doxorubicin solution, the second stage indicator monitoring is at the 2nd week, 3rd week, 4th week, 5th week, 6th week and 7th week after the animal model is injected with doxorubicin solution, and the third stage indicator monitoring is at the 8th week after the animal model is injected with doxorubicin solution.

3. The detection method based on doxorubicin-induced multiple organ damage according to claim 1, characterized in that: In the first stage indicator monitoring and the second stage indicator monitoring, monitoring the blood sample of the animal model includes: 1 mL of blood was drawn from the vein of the animal model and allowed to stand for 30 minutes, and the serum in the blood was analyzed at 4°C. The serum was tested to obtain the index parameters of serum creatinine, urea nitrogen, troponin I, alanine aminotransferase, aspartate aminotransferase, total bilirubin, glutamyl transferase, and alkaline phosphatase in the blood sample.

4. The detection method based on doxorubicin-induced multiple organ damage according to claim 1, characterized in that: In the first stage indicator monitoring and the second stage indicator monitoring, the monitoring of the heart of the animal model by B-ultrasound includes: The left ventricular ejection fraction, left ventricular shortening fraction, left ventricular end-diastolic volume and left ventricular end-systolic volume of the animal model were detected by an ultrasonic detector.

5. The detection method based on doxorubicin-induced multiple organ damage according to claim 1, characterized in that: Before monitoring the third-stage indicators of the animal model, the heart, liver and kidney of the animal model are first obtained, which includes: Eight weeks after the animal model was injected with doxorubicin solution, the animal model was anesthetized with isoflurane, the abdominal cavity of the animal model was opened along the midline of the abdomen, the chest cavity was opened along the diaphragm and the sternal costal cartilage, the inferior vena cava was cut off, and physiological saline was perfused through the abdominal aorta. The heart, liver and kidney were removed after the blood stains on the heart, liver and kidney faded.

6. The detection method based on doxorubicin-induced multiple organ damage according to claim 5, characterized in that: In the third stage of indicator monitoring, monitoring the weight of the heart, liver and kidney of the animal model includes: The heart, liver and kidney were weighed, the ratio of the organ weight to the body weight of the animal model was calculated, and after weighing, the heart, liver and kidney were immersed in 10% formalin for preservation.

7. The method for detecting multiple organ damage induced by adriamycin according to claim 6, characterized in that: In the third stage of indicator monitoring, monitoring of pathological sections of the heart, liver and kidney of the animal model includes: Monitoring of pathological sections of the heart, liver and kidneys of the animal model includes: Paraffin tissue sections were made from the heart, liver, and kidneys immersed in 10% formalin, and the pathological sections were stained and scanned panoramically using a section scanner. The thickness of the cardiac ventricular wall of the stained pathological sections was measured, the percentage of cardiac fibrosis area was scanned, the injury scores of hepatocyte degeneration, hepatocyte necrosis, and liver inflammatory cell infiltration were measured, the percentage of liver fibrosis area was scanned, the changes in kidney damage were analyzed, and the percentage of kidney fibrosis area was scanned.

8. The detection method based on doxorubicin-induced multiple organ damage according to claim 7, characterized in that: The pathological sections were stained with hematoxylin and eosin, under which: The cardiac ventricular wall thickness, hepatocyte degeneration, hepatocyte necrosis, liver inflammatory cell infiltration injury score and kidney injury changes were measured in the stained pathological sections; Staining of pathological sections also includes Masson staining, under which: The scanned areas included the percentage of cardiac fibrosis, the percentage of liver fibrosis, and the percentage of kidney fibrosis.

9. The detection method based on doxorubicin-induced multiple organ damage according to claim 1, characterized in that: The preparation of the doxorubicin solution comprises: Take doxorubicin powder, add physiological saline, and mix the doxorubicin powder and the physiological saline by vortexing and ultrasonication until there are no particles visible to the naked eye in the solution. The concentration of the doxorubicin solution is 1 mg / mL.

10. A model of multiple organ damage induced by doxorubicin, characterized in that: The model is used for the detection method based on doxorubicin-induced multi-organ damage as described in any one of claims 1 to 9.

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