A method for constructing a rat model of chemotherapy-induced phlebitis

Abstract

The application belongs to the technical field of medical animal model modeling, and provides a simple and easy-to-operate model construction method which can simulate the characteristics of clinical chemotherapy phlebitis to solve the problems of complicated replication method and lack of clinical typical characteristics of the current chemotherapy phlebitis animal model. The model agent is administered to the dorsal vein of the rat foot, and the best replication scheme of the chemotherapy phlebitis rat model is determined by investigating the concentration, dose and duration. The chemotherapy phlebitis rat model is replicated by using vinorelbine physiological saline solution with a concentration of 2-5 mg / ml and a total dose of ≤3 mg / kg. The local characterization of the dorsal foot and the foot swelling rate on the next day after modeling meet the diagnostic criteria of chemotherapy phlebitis. The pathological characteristics of chemotherapy phlebitis can be observed in the blood vessel pathological section under a light microscope and an intima scanning electron microscope, and the duration is 7 days. The model has the advantages of simple preparation method, clear quality control index, long maintenance time, low preparation cost and close to human diseases.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of medical animal model modeling, and particularly relates to a construction method of a rat model of chemotherapy phlebitis. BACKGROUND

[0002] The mechanism of chemotherapy phlebitis mainly refers to that after a strongly irritating liquid medicine enters a vein, the vascular endothelial cells are dehydrated, hypoxic, hyperemic and necrotic. The damaged vascular intima causes local platelet aggregation, thrombosis, and white blood cell infiltration into the media layer of the vein, and then causes the vein to be red, swollen, painful, discolored or hardened to a cord-like shape. The severity is related to the physicochemical properties of the drug, the drug concentration, the infusion time, the infusion volume and the drug exosmosis, etc. The American Society for Vascular Access Nursing divides phlebitis into five grades, and the most severe standard is that the infusion site is painful with redness or edema, the length of the cord-like object that can be touched is greater than 2.5 cm, and pus flows out.

[0003] At present, there is no recognized effective method and drug for treating chemotherapy phlebitis in clinic. Generally, cold compress, ultrashort wave physiotherapy and infrared radiation are used for symptomatic treatment in the acute phase, and serious cases use magnesium sulfate hot compress, sterile water colloidal dressing, vasodilators, local anesthetics, glucocorticoids, anticoagulants and other drugs, but the overall curative effect is still not satisfactory. Since most antitumor drugs belong to vesicants or have strong irritation, chemotherapy phlebitis often occurs in tumor patients in clinic, which not only increases the psychological burden and physical pain of the patients, but also seriously affects the orderly progress of the chemotherapy plan.

[0004] At present, most of the animal models of chemotherapy phlebitis use rabbit auricular marginal vein and mouse tail vein to give chemotherapy drugs. The rabbit auricular marginal vein is superficial and clear, with less hair, which is beneficial to operation and observation, and is usually the first choice for modeling of chemotherapy phlebitis. The disadvantage is that the rabbit is relatively large, and the amount of drug given is relatively large. The pain and discomfort caused by the infusion of chemotherapy drugs often cause the experimental rabbits to struggle repeatedly, thereby affecting the operation and easily causing drug leakage. Secondly, the rabbit auricular marginal vein is relatively thin, and the technical requirements for venipuncture are relatively high, which easily causes leakage of chemotherapy drugs and brings difficulties to repeated venipuncture. As for the mouse, the volume is small, the weight is light, the operation is convenient, and the cost is relatively low, but the tail vein method has high technical requirements for the operator, and during the drug administration process, if the speed is too fast or the dose is too large, it is easy to cause the death of the mouse and result in modeling failure. In addition, the surrounding tissue of the rabbit auricular marginal vein and the mouse tail vein is less, and the maintenance time after successful modeling is short, and the short-term self-healing rate is high. SUMMARY

[0005] The application provides a construction method of a rat model of chemotherapy phlebitis, which can make the performance of the animal after modeling consistent with the symptoms of clinical chemotherapy phlebitis, and the rat is convenient to fix, the price is relatively cheap, and the rat is not easy to die during the experiment.

[0006] The application is implemented by the following technical scheme: a construction method of a chemotherapy phlebitis rat model, comprising the following steps: administering vinorelbine physiological saline solution to the dorsal vein of the rat foot, the administration dose being ≤3 mg / kg, and the next day the affected limb side showing the characteristics of chemotherapy phlebitis, the pathological changes and the intimal microscopic structure changes of the vein being consistent with the damage characteristics of chemotherapy phlebitis, and the duration being up to 7 days.

[0007] The rat: the weight being 300-400 g, including Wistar and Sprague dawley strains, and the gender being unlimited;

[0008] The vinorelbine physiological saline solution: the concentration being 2-5 mg / ml, and the administration dose of the rat being ≤3 mg / kg of the body weight.

[0009] The chemotherapy phlebitis characteristics: redness and swelling, vein cord, and the foot swelling rate still being >50% on the 7th day;

[0010] The vein pathological characteristics: thrombus can be seen in the lumen, perivascular tissue edema, inflammatory cell infiltration, and part of the endothelial cells falling off;

[0011] The intimal microscopic structure changes: the intimal surface being rough, leukocytes and platelets gathering, and the endothelial cells being sparse.

[0012] The reasons for selecting the rat dorsal vein for modeling are as follows: (1) the rat dorsal vein is superficial and clear, easy to operate and observe; (2) the rat is easy to obtain and convenient to fix; and (3) the surrounding tissue of the rat dorsal vein is more, and is basically consistent with the chemotherapy phlebitis symptoms and pathological changes of the patient, and can simulate the chemotherapy phlebitis of the human.

[0013] The application has the following beneficial effects compared with the prior art:

[0014] 1. The preparation method is safe and simple: the adverse reactions of vinorelbine have dose-limiting toxicity, which is manifested as bone marrow suppression, the application selects the appropriate concentration of vinorelbine by detecting the white blood cell count to ensure that it is safe and non-toxic, and an ideal chemotherapy phlebitis rat model can be prepared.

[0015] 2. The quality control index is clear: after the intervention, the gross observation, foot volume swelling rate, scanning electron microscope ultrastructure observation, HE staining and other indicators have obvious change rules, and can be used as important model quality control indicators, and have good repeatability.

[0016] 3. The symptoms are relatively stable: after the model is successfully prepared, the chemotherapy phlebitis state lasts for a long time, and can meet the basic needs of the experiment.

[0017] 4. The preparation cost is low: the intervention experiment reagent of the model is vinorelbine tartrate injection, which is relatively cheap.

[0018] 5. Disease characteristics: Compared with rabbit ear marginal vein and mouse tail vein, rat dorsal foot vein is more suitable for clinical disease characteristics and easier to observe. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 General observation of rat dorsal foot vein for different concentration administration groups (on the seventh day of modeling);

[0020] Figure 2 HE staining comparison of rat dorsal foot vein for different concentration administration groups (200 times);

[0021] Figure 3 General observation of rat dorsal foot vein for different sampling time groups;

[0022] Figure 4 HE staining comparison of rat dorsal foot vein for different sampling time groups (200 times);

[0023] Figure 5 Scanning electron microscope comparison of rat dorsal foot vein for different sampling time groups (1000 times). DETAILED DESCRIPTION

[0024] In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be described clearly and completely below. Obviously, the described embodiments are part of, but not all of the embodiments of the present application; based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative work fall within the scope of the present application.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs, and the materials cited and referenced in the present disclosure are incorporated by reference.

[0026] All art-known functional alternatives to the described specific embodiments are intended to be encompassed by this application.

[0027] The experimental methods in the following examples are all conventional methods unless otherwise specified. The instruments and equipment used in the following examples are all conventional laboratory instruments and equipment unless otherwise specified; the experimental materials used in the following examples are all conventional biochemical reagents unless otherwise specified.

[0028] I. Experimental materials

[0029] 1、Experimental animals: SPF level 8-week-old male SD rats. The experimental animals were provided by Beijing Huafukang Biotechnology Co., Ltd., license number: SCXK (Jing 2019-0008). The experiment was carried out after being fed for one week to adapt to the laboratory environment. During feeding, the animals were allowed to eat and drink freely, and the light / dark cycle was 12 hours. The temperature and humidity were suitable.

[0030] 2、Experimental drugs: vinorelbine tartrate (Ganuo, Jiangsu Lianyungang Haosen Pharmaceutical Co., Ltd., specification: 10 mg / ml), physiological saline (batch: 2103041902).

[0031] 3、Chemical reagents: isoflurane, Shandong Keyuan Pharmaceutical Co., Ltd.; paraformaldehyde Shanghai McLean Biotech Co., Ltd.; NaH2PO4 2H2O, Shanghai McLean Biotech Co., Ltd.; Na2HPO4 12H2O, Shanghai McLean Biotech Co., Ltd.; glutaraldehyde fixing solution, Nanjing Sunbeiqia Biotechnology Co., Ltd.

[0032] 4、Preparation of drugs and reagents: vinorelbine and physiological saline were prepared into corresponding concentration solutions, which were prepared and used immediately; 4% paraformaldehyde solution was prepared by adding 40 g of paraformaldehyde, 2.96 g of NaH2PO4 2H2O, 28.7 g of Na2HPO4 12H2O, and 600 ml of distilled water was added to prepare a solution, which was dissolved until completely clear, then diluted to 1000 ml, and stored at room temperature in the dark.

[0033] 5、Main equipment: pipette, Dalongxingchuang Experimental Instruments (Beijing) Co., Ltd.; small animal special inhalation anesthesia machine, USA Matrx; 1 ml syringe, Jiangsu Zhiyu Medical Instrument Co., Ltd.; 0.45*0.15 infusion needle, Jiangxi Hongda Medical Instrument Co., Ltd.; electronic scale, Taiyuan Aviation Instrument Co., Ltd.; foot volume measuring instrument, Chengdu Tailian Software Co., Ltd.; automatic five-classification animal blood analyzer, USA Drew Scientific; tissue embedding box, Jiangsu Shetai Experimental Equipment Co., Ltd.; paraffin sectioning machine, Thermo Scientific; tissue embedding instrument, Hubei Taikang Medical Equipment Co., Ltd.; upright microscope, Japan Olympus; scanning electron microscope, Japan HITACHI.

[0034] II. Experimental methods and results

[0035] 1、Dose screening

[0036] Grouping: 40 rats were randomly divided into blank control group, modeling dose 3 mg / kg, 6 mg / kg and 9 mg / kg, a total of 4 groups, 10 rats in each group.

[0037] Method of administration: The rats were placed in a small animal inhalation anesthesia machine and given 2% isoflurane anesthesia, the dorsal foot hair was removed, the rubber band was laced at the root of the hind limb to expose the dorsal foot vein, and the intravenous administration was performed at the dorsal foot 1 cm from the fourth metacarpophalangeal joint. The blank control group was given normal saline 0.1 ml by intravenous administration in the dorsal foot; the rest of the groups were given corresponding doses of vinorelbine, and the rubber band was loosened after 5 minutes.

[0038] Observation index: The white blood cell count was observed once every 48 h by orbit blood sampling; the mortality within 7 days was observed. The mortality was calculated according to the following formula. Mortality = (total number of deaths within 7 days after modeling) / total number of modeling 100%.

[0039] Test results:

[0040] A, white blood cell count: the results are shown in Table 1. Compared with the blank control group, the white blood cell count of the 3 mg / kg group decreased after the first day of modeling, and there was a significant difference compared with the blank control group (p<0.05), and there was no significant difference compared with the blank control group on the 7th day; the white blood cell count of the 6 mg / kg and 9 mg / kg groups decreased after the first day of modeling, and continued to decrease after the third day, and the white blood cell count on the 7th day increased compared with the 5th day, but compared with the blank control group, p<0.001, the difference was extremely significant.

[0041] Table 1 Effect of different doses of administration on white blood cell count of rats , n=10

[0042]

[0043] Note: compared with the blank control group, p<0.05, p<0.001.

[0044] B, mortality: the rats in the blank control group had no abnormal reaction, and the rats were active, and the mental condition was good, and the stool and urine were normal; the 3 mg / kg rats had reduced food and water intake on the second day, and recovered on the third day, and none died within 7 days; some rats in the 6 mg / kg group had diarrhea, quiet and lazy, and the symptoms of dull hair color after modeling, 1 died on the second day, 2 died on the third day, a total of 3 died, and the mortality was 30%; some rats in the 9 mg / kg group had quiet and lazy, reduced appetite, diarrhea, and mental debilitation after modeling, 2 died on the second day, 1 died on the third day, 1 died on the fourth day, and 1 died on the sixth day, a total of 6 died, and the mortality was 60%.

[0045] Conclusion: The administration dose of the rat dorsal vein chemotherapy phlebitis model should be selected below 3 mg / kg, otherwise bone marrow suppression will occur, and even death will occur.

[0046] 2. Screening of modeling agent concentration

[0047] Grouping: 30 rats were randomly divided into 5 groups: blank control group, modeling agent at concentrations of 2 mg / ml, 3 mg / ml, 4 mg / ml and 5 mg / ml, with 6 rats in each group.

[0048] Administration method: Rats were anesthetized with 2% isoflurane using a small animal-specific inhalation anesthesia machine. Hair was removed from the dorsum of the foot, and the hind limb roots were ligated with a rubber band to fully expose the dorsal vein of the foot. The drug was administered intravenously 1 cm from the fourth metacarpophalangeal joint on the dorsum of the foot. In the blank control group, 0.1 ml of normal saline was administered via the dorsal vein of the foot. The other groups were given the corresponding dose of vinorelbine. The rubber band was released after 5 minutes.

[0049] Observation indicators: Rat body weight was measured daily, and the condition of the treated hind limb was recorded. The volume of the treated hind limb was measured every 48 hours. The swelling rate of the affected limb was calculated using the following formula: Swelling rate = (Daily volume after modeling - Initial volume before modeling) / Initial volume before modeling 100%. Blood was drawn from the orbit once for white blood cell count. On the 7th day of modeling, after intraperitoneal anesthesia, the skin of the dorsum of the foot was incised to free a 2cm specimen of the dorsal vein of the foot, which was then placed in 4% paraformaldehyde solution for paraffin sectioning and HE study.

[0050] Test results:

[0051] A. Gross observation of the affected limb: Results are as follows Figure 1 As shown (day 7 of modeling), the blank control group had no symptoms; the 2mg / ml group had redness and slight swelling on the dorsum of the foot; the 3mg / ml group had redness, slight swelling, and ulceration and crusting on the dorsum of the foot; the 4mg / ml group had redness, swelling, necrosis and crusting of the surrounding tissue, peeling, and other symptoms on the dorsum of the foot; the 5mg / ml group had extreme swelling of the hind limb and symptoms such as necrosis and ulceration of muscle and skin tissue, and purulent discharge.

[0052] B. Swelling rate of affected limbs: The results are shown in Table 2. In the 2 mg / ml group, the paw swelling rate increased to 33% on day 3, and stabilized at around 20% on days 5 and 7. In the 3 mg / ml group, the swelling rate was the highest at 61% on day 3 (p < 0.001 compared with the control group), and decreased to 50% on day 7 (p < 0.05 compared with the control group), which was statistically significant. The 4 mg / ml group had a relatively large swelling rate, reaching 83% on day 3 and decreasing to 73% on day 7 (p < 0.001 compared with the control group), which was statistically significant. The 5 mg / ml group had the highest swelling rate, reaching 132% on day 3 and then decreasing to 99% on day 7 (p < 0.001 compared with the control group), which was statistically significant. Overall, rats in all groups showed varying degrees of paw swelling on the first day after modeling, which was more severe on days 3-5, and showed a tendency to improve on days 5-7, but still exhibited significant swelling.

[0053] Table 2. Effects of different concentrations of the drug on the swelling rate of the affected limb in rats ( (n=6)

[0054]

[0055] Note: Compared with the blank control group, p < 0.05 p < 0.001.

[0056] C. Histological section of the dorsal vein of the foot: Results are as follows Figure 2 As shown, in the blank control group, endothelial cells were neatly arranged; in the 2 mg / ml group, there was perivascular edema and some endothelial cell shedding; in the 3 mg / ml group, some endothelial cells shed, perivascular tissue edema, and inflammatory cell infiltration; in the 4 mg / ml group, a large number of red blood cells aggregated in the lumen, perivascular tissue edema, and a large number of inflammatory cells infiltrated; in the 5 mg / ml group, thrombus formation was visible in the lumen, a large number of endothelial cells shed, and perivascular tissue edema was more severe.

[0057] Conclusion: The drug concentrations of 2 mg / ml and 3 mg / ml resulted in milder modeling with shorter duration and spontaneous recovery; the concentration of 4 mg / ml achieved a 100% modeling rate with a longer duration and spontaneous recovery; the concentration of 5 mg / ml resulted in more severe modeling with perivenous necrosis and the longest duration.

[0058] 3. Determining the model duration

[0059] Grouping: 24 rats were randomly divided into four groups: blank control group, observation point 48h, 96h, and 168h, with 6 rats in each group.

[0060] Administration method: Rats were anesthetized with 2% isoflurane using a small animal-specific inhalation anesthesia machine. Hair was removed from the dorsum of the foot, and the hind limb roots were ligated with a rubber band to fully expose the dorsal vein of the foot. The drug was administered intravenously 1 cm from the fourth metacarpophalangeal joint on the dorsum of the foot. In the blank control group, 0.1 ml of normal saline was administered via the dorsal vein of the foot; in the other groups, 0.1 ml of vinorelbine at a concentration of 4 mg / ml was administered, and the rubber band was released after 5 minutes.

[0061] Specimen collection: After intraperitoneal anesthesia at the corresponding time points, the skin of the dorsum of the foot was cut open and the dorsal vein specimen of the foot was freed by 4 cm. It was divided into two parts. One part was fixed in 4% paraformaldehyde for paraffin sectioning and HE study, and the other part was fixed in 2.5% glutaraldehyde for scanning electron microscopy observation.

[0062] Test results:

[0063] A. General observation: Results are as follows Figure 3As shown, the blank control group was asymptomatic; the 48h group had redness and swelling on the dorsal foot, with slight ulceration; the 96h group had redness, swelling, and ulceration and scabbing on the dorsal foot; and the 168h group had redness, swelling, and necrosis of the surrounding tissue, scabbing, and exfoliation on the dorsal foot.

[0064] B, dorsal foot vein tissue sections: the results are shown in Figure 4 As shown, the endothelial cells in the blank control group were arranged in an orderly manner; in the 48h group, thrombosis was visible in the lumen and was more than 2 / 3 of the vascular section, a large number of endothelial cells were shed, and the perivascular tissue was severely edematous; in the 72h group, some endothelial cells were shed, the perivascular tissue was edematous, and inflammatory cells infiltrated; in the 96h group, red blood cells were aggregated in the lumen, the perivascular tissue was edematous, and a large number of inflammatory cells were accumulated and stacked in the extravascular tissue; and in the 168h group, the lumen was narrowed, the vessel wall was thinned, and a small number of inflammatory cells infiltrated.

[0065] C, intimal microstructure of the dorsal foot vein: the results of scanning electron microscopy observation are shown in Figure 5 In the blank control group, the tight junctions of the endothelial cells and the cell nuclei were clearly visible. In the 48h group, a large area of the intimal surface of the blood vessels was damaged, and leukocytes and platelets were aggregated on the damaged intimal surface. In the 96h group, the intimal surface of the blood vessels was rough, the tight junctions of the endothelial cells were sparse, the intimal surface of the blood vessels was damaged, and there was some proliferation. In the 168h group, the tight junctions of the endothelial cells were sparse, the intimal surface of the blood vessels was damaged, resulting in some cells remaining in the intimal surface of the blood vessels, and there were also newly formed blood vessel endothelial cells, which were flat in shape and had clear cell boundaries.

[0066] Conclusion: According to the gross observation, the acute phase of the inflammatory response was 2-4 days, the histopathological observation, and the scanning electron microscopy observation showed that the intimal surface was damaged and a large number of leukocytes were aggregated. The chronic phase of the inflammation was 4-7 days, the gross observation showed that the surrounding tissue of the blood vessels was scabbed, the wound was reduced in size, and the redness and swelling were reduced; the histopathological observation and the scanning electron microscopy observation showed that the inflammatory cells were reduced on the intimal surface, and there were newly formed endothelial cells.

[0067] 4, Model verification experiment

[0068] Grouping: 12 rats were randomly divided into a blank control group and a model group, 6 rats in each group.

[0069] Dosing method: The rats were placed in a small animal special inhalation anesthesia machine and given 2% isoflurane anesthesia, the hair on the dorsal foot was removed, the hind limb was laced with a rubber band, the dorsal foot vein was fully exposed, and the drug was administered intravenously at a distance of 1 cm from the fourth metacarpophalangeal joint. The blank control group was given normal saline 0.1 ml intravenously on the dorsal foot; the model group was given vinorelbine with a concentration of 4 mg / ml 0.1 ml, and the rubber band was loosened after 5 minutes.

[0070] Results:

[0071] General observation: the blank control group had no symptoms; the model group had redness and swelling on the dorsal foot for 2-4 days, and even necrosis, ulceration and other symptoms in the surrounding tissue; the dorsal foot was red, swollen, and the surrounding tissue had scabbing, exuviation and other symptoms for 4-7 days.

[0072] Dorsal foot vein tissue section: the endothelial cells in the blank control group were arranged in order; in the model group, red blood cells aggregated in the lumen for 2-4 days, even thrombosis formed, a large number of endothelial cells fell off, the perivascular tissue was severely edematous, and inflammatory cells infiltrated; the lumen was narrowed and the wall was thinned for 4-7 days, and a small amount of inflammatory cells infiltrated.

[0073] Dorsal foot vein scanning electron microscope observation: the endothelial cell tight junction and nucleus can be clearly seen in the blank control group. In the model group, a large area of endothelial cells on the vascular intima surface were damaged for 2-4 days, and leukocytes and platelets aggregated on the damaged intima surface. For 4-7 days, the endothelial cell tight junction was arranged sparsely, the vascular intima surface was damaged, resulting in some cells remaining in the intima, and there were also newly formed vascular endothelial cells, which were flat in shape and had clear cell boundaries.

[0074] Conclusion: the modeling rate can reach 100% at a concentration of 4 mg / ml, the duration is longer and can be self-healing, which is consistent with the clinical symptoms.

[0075] General observation: for 2-4 days, the acute inflammatory reaction, the surrounding tissue of the blood vessels was red and swollen, ulcerated, discolored or hardened to cord-like inflammation; for 4-7 days, the chronic inflammatory period, the surrounding tissue of the blood vessels was scabbed, the wound was reduced, and the swelling was reduced.

[0076] In summary, the rat dorsal vein chemotherapy phlebitis model can be concluded as follows through leukocyte count, mortality, body weight, hind limb swelling rate, histopathological observation, scanning electron microscope observation and other indicators: (1) the dosage should be selected below 3 mg / kg, otherwise bone marrow suppression and even death will occur; (2) the vinorelbine concentration is 2-5 mg / ml, the modeling rate can reach 100% at a concentration of 4 mg / ml, the duration is longer and can be self-healing, which is consistent with the clinical symptoms. (3) According to the general observation, for 2-4 days, the acute inflammatory reaction, the scanning electron microscope observation showed that the intima surface was damaged and a large number of leukocytes aggregated. For 4-7 days, the chronic inflammatory period, the general observation showed that the surrounding tissue of the blood vessels was scabbed, the wound was reduced, and the swelling was reduced; the histopathological observation and scanning electron microscope observation showed that the inflammatory cells in the intima surface were reduced, and there were new endothelial cells.

[0077] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present application, and are not intended to limit the present application; although the present application has been described in detail with reference to the above embodiments, those skilled in the art should understand that the technical solutions recorded in the above embodiments can be modified, or some or all of the technical features can be replaced by equivalents; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the scope of the technical solutions of the embodiments of the present application.

Claims

1. A method for constructing a rat model of chemotherapy-induced phlebitis, characterized by: The rats are given vinorelbine in normal saline solution by the dorsal vein of the foot, with a dose of ≤3 mg / kg, and the next day the affected limb shows the characteristics of chemotherapy-induced phlebitis, and the venous pathology and intimal microstructure changes are consistent with the characteristics of chemotherapy-induced phlebitis, with a duration of 7 days; the concentration of the vinorelbine in normal saline solution is 2-5 mg / ml.

2. The method for constructing a rat model of chemotherapy-induced phlebitis according to claim 1, characterized in that: The rats are of the Sprague dawley strain, with a body weight of 300-400 g.

3. The method for constructing a rat model of chemotherapy-induced phlebitis according to claim 1, characterized in that: The characteristics of chemotherapy-induced phlebitis are: redness, phlebectasia, and a foot swelling rate of >50% on the 7th day; The venous pathology characteristics are: thrombus in the lumen, perivascular tissue edema, inflammatory cell infiltration, and partial endothelial cell shedding; The intimal microstructure changes are: rough intimal surface, leukocyte and platelet aggregation, and sparse endothelial cell arrangement.

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