Application of Hamaudol in improving acute kidney injury and intestinal barrier function

Abstract

The present invention discloses the application of Hamaudol in improving acute kidney injury and intestinal barrier function, and belongs to the field of drug development technology. The present invention finds that by intraperitoneally injecting the Chinese medicine monomer Hamaudol into mice, the intestinal barrier function can be significantly improved, the expression of tight junction proteins ZO-1 and Occludin in the intestinal tract of mice can be increased, and the serological indicators of acute kidney injury can be reduced at the same time, the pathological changes of renal tubular epithelial cells in mice with acute kidney injury can be improved, the expression of inflammatory factors in the kidney can be downregulated, and apoptosis and oxidative damage can be improved. Thus, acute kidney injury is prevented and treated, and a new target is provided for the treatment of acute kidney injury.

Description

Technical Field

[0001] The invention relates to application of Hamaudol in improving acute kidney injury and intestinal barrier function, and belongs to the technical field of drug development. Background Art

[0002] Acute kidney injury is a clinical syndrome caused by a variety of reasons, which is manifested by sudden and persistent rapid decline in renal function. It is characterized by a sharp deterioration of renal function in a short period of time, a decrease in solute clearance capacity and glomerular filtration rate. Improper treatment may turn into chronic kidney disease or spread to other organs, causing serious damage to the body. Symptoms include decreased renal function, and common symptoms include fatigue, lack of appetite, decreased urine volume and darker urine color. The current treatment principle is to identify and correct reversible causes as early as possible, take timely intervention measures to avoid further damage, provide appropriate nutritional support, actively prevent and treat complications, and renal replacement therapy can be performed for severe patients. At present, it is difficult to achieve ideal results in the treatment of AKI, and new therapeutic targets need to be explored.

[0003] The gastrointestinal tract is considered to be the largest immune organ in the body and plays a core role in regulating immune homeostasis. The intestinal barrier mainly includes mechanical barriers, ecological barriers and immune barriers, including intestinal flora, mucus layer, intestinal epithelial cells and intercellular junctions. Intestinal barrier damage can lead to increased intestinal permeability and polarity changes, causing endotoxins and bacterial pathogens to enter the blood circulation, resulting in local or systemic inflammatory reactions and inducing enterogenic immune responses. Previous studies have shown that restoring the expression of tight junction proteins can reverse microbiota dysbiosis, prevent toxins and pathogens from entering the systemic circulation through the intestinal barrier, and thus reduce inflammation and the progression of AKI.

[0004] Hamaudol, a traditional Chinese medicine monomer, is a chromone isolated from the traditional Chinese medicine Saposhnikovia divaricata. It has a significant inhibitory effect on the activity of cyclooxygenase (COX)-1 and COX-2. Its molecular formula is C 15 H 16 O 5 , and has effective analgesic and anti-inflammatory effects. However, its application in acute kidney injury is relatively rare and needs further exploration. Summary of the invention

[0005] The purpose of the present invention is to provide the use of a Chinese medicine monomer Hamaudol in the preparation of a product for improving acute kidney injury and intestinal barrier. The present invention focuses on the effect of intestinal mucosal damage on AKI and studies the role of a Chinese medicine monomer Hamaudol in AKI and intestinal barrier damage.

[0006] To achieve the above purpose and other related purposes, the technical solution provided by the present invention is: application of the traditional Chinese medicine monomer Hamaudol in the preparation of products for improving acute kidney injury and intestinal barrier function.

[0007] The present invention provides a drug for treating and / or alleviating acute kidney injury, or for treating and / or alleviating intestinal barrier damage caused by acute kidney injury. The drug is any pharmaceutically acceptable dosage form prepared with chorilol as an active ingredient and pharmaceutically acceptable excipients.

[0008] In one embodiment of the present invention, the dosage form of the drug includes, but is not limited to, tablets, dispersible tablets, lozenges, orodisintegrating tablets, sustained-release tablets, capsules, soft capsules, pills, granules, injections, powder injections or aerosols.

[0009] In one embodiment of the present invention, the drug further comprises a drug carrier, and the drug carrier comprises one or more of fillers, binders, wetting agents, disintegrants, lubricants, and flavoring agents commonly used in medicine.

[0010] In one embodiment of the present invention, the hydroxylamine chemical formula is C 15 H 16 O 5 , whose structural formula is as follows:

[0011]

[0012] The present invention also provides the use of the above-mentioned chorilol in preparing a drug for treating and / or alleviating acute kidney injury, and also provides the use of the above-mentioned chorilol in preparing a drug for treating and / or alleviating intestinal barrier damage caused by acute kidney injury.

[0013] In one embodiment of the present invention, the use of the traditional Chinese medicine monomer Hamaudol in improving acute kidney injury and intestinal barrier is characterized in that the product is used for at least one of (a) to (d):

[0014] (a) Treating patients with acute kidney injury;

[0015] (b) increasing the expression of intestinal tight junction proteins in patients with acute kidney injury;

[0016] (c) Reduce the serum endotoxin level caused by acute kidney injury in patients, and downregulate the biochemical indicators of acute kidney injury such as serum creatinine, urea nitrogen and serum cystatin levels;

[0017] (d) down-regulating the expression levels of KIM-1 and NGAL gene mRNA in the kidneys of patients with acute kidney injury;

[0018] (e) down-regulate the expression levels of renal inflammatory genes IL-1β, IL-6, MCP-1, and COX-2 in patients with acute kidney injury;

[0019] (f) Improve renal tissue pathology in patients with acute kidney injury;

[0020] (g) Treatment of acute kidney injury induced by renal ischemia-reperfusion, accompanied by intestinal mucosal damage.

[0021] In one embodiment of the present invention, the acute kidney injury is acute kidney injury caused by ischemia-reperfusion.

[0022] In one embodiment of the present invention, the molecular formula of the traditional Chinese medicine monomer Hamaudol is C 15 H 16 O 5 .

[0023] In one embodiment of the present invention, the intestinal tight junction proteins include ZO-1 and Occludin expression changes.

[0024] In one embodiment of the present invention, the acute kidney injury biomarker genes KIM-1 and NGAL genes are down-regulated after Hamaudol treatment, including at the mRNA level.

[0025] In one embodiment of the present invention, the subject is a mammal or a human.

[0026] In one embodiment of the present invention, the drug contains choridene as an effective ingredient, and also contains a drug carrier and a pharmaceutically acceptable excipient.

[0027] In one embodiment of the present invention, the drug carrier includes one or more of fillers, binders, wetting agents, disintegrants, lubricants, and flavoring agents commonly used in medicine.

[0028] In one embodiment of the present invention, the dosage form of the drug includes, but is not limited to, tablets, dispersible tablets, lozenges, orodisintegrating tablets, sustained-release tablets, capsules, soft capsules, pills, granules, injections, powder injections or aerosols.

[0029] In one embodiment of the present invention, the hydroxylamine chemical formula is C 15 H 16 O 5 , whose structural formula is as follows:

[0030]

[0031] Beneficial Effects

[0032] The present invention provides a new application of the traditional Chinese medicine monomer Hamaudol, namely:

[0033] (1) The Chinese medicine monomer Hamaudol can improve acute kidney injury induced by ischemia-reperfusion, repair intestinal barrier function, and increase the expression of tight junction proteins in intestinal epithelial cells.

[0034] (2) The Chinese medicine monomer Hamaudol can reduce the levels of serum urea nitrogen, creatinine and cystatin C that are elevated due to renal ischemia-reperfusion injury. The Chinese medicine monomer Hamaudol reduces the shedding of renal tubular epithelial cells and the shedding of renal tubular brush border, which improves acute kidney injury and provides a new target for the treatment of acute kidney injury. The expression of intestinal tight junction proteins increases and tends to normal levels, which has the effect of improving intestinal barrier dysfunction. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 :The intervention of Chinese medicine monomer Hamaudol alleviates the decline in renal function caused by IRI; Among them, (A) is the change of serum urea nitrogen (BUN); (B) is the change of serum creatinine (Scr); (C) is the change of serum cystatin C.

[0036] Figure 2 :The intervention of Chinese medicine monomer Hamaudol alleviates renal pathological damage caused by IRI; Among them, (A) HE staining; (B) statistical relative value of renal tubular damage.

[0037] Figure 3 : The intervention Chinese medicine monomer Hamaudol down-regulated the expression levels of KIM-1 and NGAL gene mRNA in the kidney; among them, (A) the relative expression statistics of kidney KIM-1 gene mRNA; (B) the relative expression statistics of kidney NGAL gene mRNA.

[0038] Figure 4 :The intervention of the Chinese medicine monomer Hamaudol down-regulated the expression level of inflammatory gene mRNA in the kidney and improved apoptosis and oxidative damage; among them, (A) relative expression statistics of mRNA of renal inflammatory genes IL-1β, IL-6, MCP-1, and COX-2; (B) renal TUNEL staining and relative expression statistics; (C) renal oxidative damage DHE staining and relative expression statistics.

[0039] Figure 5 :The intervention of Chinese medicine monomer Hamaudol improves intestinal barrier damage caused by IRI; Among them, (A) Occludin immunohistochemistry staining; (B) Occludin expression statistical relative value in immunohistochemistry; (C) ZO-1 immunofluorescence staining; (D) ZO-1 expression statistical relative value in immunofluorescence. DETAILED DESCRIPTION

[0040] In order to further explain the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the specific implementation mode, structure, characteristics and effects of the present invention are described in detail below in conjunction with the accompanying drawings and preferred embodiments.

[0041] The experimental methods used in the following examples are conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples are all commercially available unless otherwise specified.

[0042] The common feeds involved in the following examples were purchased from: Weitong Lihua Experimental Animal Technology Co., Ltd.;

[0043] The hamaudol was purchased from Aladdin Reagent Co., Ltd. The CAS number of the hamaudol is 735-46-6; the chemical formula is: 15 H 16 O 5 ; The structural formula is as follows:

[0044]

[0045] The mice used in the following examples are C57BL / 6 mice, purchased from SpEffect Biotechnology Company.

[0046] The serum urea nitrogen detection kit, serum creatinine detection kit, and serum cystatin C detection kit involved in the following examples were purchased from Nanjing Jiancheng Bioengineering Institute.

[0047] The detection methods involved in the following embodiments are as follows:

[0048] HE staining:

[0049] Mice were anesthetized and killed, and the kidneys were fixed in formaldehyde. The specimens were dehydrated with ethanol gradient, embedded in paraffin, and cut into paraffin sections with a thickness of 5 μm. HE staining was used to evaluate tubular injury, and the digital slice scanning system of 3DHISTECH, Hungary was used for scanning. A semi-quantitative scoring system was used to evaluate the severity of acute kidney injury: based on tubular dilatation, tubular formation, tubular atrophy, loss of brush borders, and the percentage of epithelial necrosis in the outer medullary region to the total number of tubules. 0 points, no injury; 1 point, injury ≤ 10%; 2 points, injury between 11%-25%; 3 points, injury between 26-25%; 4 points, injury between 46-75%; 5 points, injury ≥ 76%.

[0050] TUNEL staining:

[0051] To determine the amount of apoptotic cells in kidney tissue, kidney tissue sections were dewaxed, rehydrated, and antigen-retrieved with EDTA antigen retrieval solution. After washing, the sections were incubated with TUNEL reaction solution at 37°C in the dark for 1 hour, and then placed with DAPI at room temperature for 10 minutes. Finally, the slides were mounted with anti-fading mounting medium, and the stained cells were observed using a fluorescence microscope. Six non-repetitive fields of view were randomly selected for each section and images were taken. The amount of apoptosis in kidney cells was analyzed using ImageJ software.

[0052] DHE staining:

[0053] To determine the amount of oxidative damage in renal tissue, renal tissue sections were dewaxed, rehydrated, and antigen-retrieved with EDTA antigen-retrieval solution. After washing, the sections were incubated with DHE reactive oxygen species probe at 37°C in the dark for 30 min, and then placed with DAPI at room temperature for 10 min. Finally, the slides were mounted with anti-fading mounting medium, and the stained tissues were observed using a fluorescence microscope. Six non-repetitive fields of view were randomly selected for each section and images were taken. ImageJ software was used to analyze the amount of oxidative damage in renal tissue.

[0054] Immunohistochemical staining:

[0055] The mice were anesthetized and killed, and the colon was fixed in formaldehyde. The specimens were dehydrated with gradient ethanol, embedded in paraffin, and cut into paraffin sections with a thickness of 5 μm. The expression of occludin in the colon was evaluated by immunohistochemical staining. The stained tissue was observed using a Nikon upright fluorescence microscope. Six non-repetitive fields of view were randomly selected for each section and images were taken. ImageJ software was used for analysis.

[0056] Immunofluorescence staining:

[0057] Colon tissue sections were dewaxed, rehydrated, and antigen retrieval treated with EDTA antigen retrieval solution. After washing, sections were incubated with anti-ZO-1 antibody (1:200) at 4°C overnight and incubated with secondary antibody at room temperature for 1 h. Finally, slides were mounted with anti-fading mounting medium, and the stained tissues were observed using a fluorescence microscope. Six non-repetitive fields of view were randomly selected for each section and images were taken. ImageJ software was used for analysis.

[0058] Example 1: Preparation and administration of mouse model

[0059] The specific steps are as follows:

[0060] The mice were randomly divided into three groups: sham operation group, renal ischemia-reperfusion group, and Hamaudol+renal ischemia-reperfusion group. The mice in the three groups were given ordinary feed and fed freely. After one week of adaptive feeding, the model was established. The specific treatment method is as follows:

[0061] The experiment lasted a total of 15 days;

[0062] Sham operation group:

[0063] Six C57BL / 6J mice were randomly selected. After adaptive feeding for 1 week (1-7 days), they were gavaged with 0.9% NaCl buffer every day for 1 week (8-14 days). After gavage, 2% isoflurane gas was used for anesthesia. After the mice were breathing steadily and entered an anesthetized state, a small incision was made along the costal angle of their backs, and the kidneys were squeezed out in the body along the direction of the opening. After 45 minutes, the kidneys were returned without ischemia-reperfusion treatment. After the above sham operation was completed, the mice were fed for 24 hours and then given a benevolent end point.

[0064] Renal ischemia-reperfusion group (IRI group):

[0065] Six C57BL / 6J mice were randomly selected. After adaptive feeding for 1 week (1-7 days), they were gavaged with 0.9% NaCl buffer every day for 1 week (8-14 days). After gavage, 2% isoflurane gas was used for anesthesia. After the mice's breathing was stable and they entered an anesthetized state, a small incision was made along the costo-vertebral angle on their backs, and the kidneys were squeezed out along the opening direction. The renal arteries and veins were carefully separated and identified, and the artery clamps were taken to clamp them. Within 1 minute after clamping, the color of the mouse kidneys became darker and blacker, which was a successful ischemia. Each mouse's kidney was ischemic for 45 minutes, and then the artery clamps were released. When the blood was reperfused, the color of the kidneys changed from black and red to ruddy, which was a successful reperfusion. Both kidneys of each mouse were clamped at the same time. After the above reperfusion modeling was completed, the mice were fed for 24 hours and the benevolent end point was given to the mice.

[0066] Hamaudol+renal ischemia-reperfusion group:

[0067] Six C57BL / 6J mice were randomly selected. After adaptive feeding for 1 week (1-7 days), they were given intragastric administration of Hamaudol solution (30 mg / kg, Hamaudol was dissolved in 0.9% NaCl buffer solution) every day. The intragastric administration time was 1 week (8-14 days). After intraperitoneal administration, 2% isoflurane gas was used for anesthesia. After the mice breathed steadily and entered the anesthesia state, a small incision was made along the costal angle of the back, and the kidney was squeezed out along the opening direction. The renal artery and vein were carefully separated and identified, and the artery clamp was taken to clamp it. Within 1 minute after clamping, the color of the mouse kidney could be seen to darken and turn black, which was a successful ischemia. Each mouse kidney was ischemic for 45 minutes, and then the artery clamp was released. After blood was reperfused, the color of the kidney changed from black and red to ruddy, which was a successful reperfusion. Both kidneys of each mouse were clamped at the same time. After the above reperfusion modeling was completed, the mice were fed for 24 hours and the benevolent end point was given to the mice.

[0068] The intragastric dose of NaCl buffer in the renal ischemia-reperfusion group and the sham operation group was the same as that of Hamaudol solution.

[0069] Example 2: Application of the Chinese medicine monomer Hamaudol in improving acute kidney injury and intestinal barrier function

[0070] The animal experiment was the same as in Example 1. After the experiment, the relevant indicators were tested:

[0071] 1. After the modeling was completed and the feeding was continued for 24 hours, blood was collected from the eyeballs of the three groups of mice to obtain serum and test the changes in serum creatinine, urea nitrogen, and cystatin C. The results were as follows: Figure 1 shown.

[0072] The results showed that the levels of serum creatinine, urea nitrogen, and cystatin C in the sham group were 0.41±0.04μg / dL, 14.47±1.65mM / L, and 4.53±0.40ng / mL, respectively;

[0073] Under the action of ischemia-reperfusion, the levels of serum creatinine, urea nitrogen, and cystatin C in mice of the IRI group (model group) were significantly higher than those in the control group, which were 1.27±0.07μg / dL, 48.98±3.16mM / L, and 17.63±1.64ng / mL, respectively;

[0074] However, the renal injury indicators in the IRI+Hamaudol group were significantly decreased, and the levels of serum creatinine, urea nitrogen, and cystatin C in mice were 0.88±0.07μg / dL, 32.18±2.76mM / L, and 10.77±1.02ng / mL, respectively;

[0075] It can be seen that the use of the Chinese medicine monomer Hamaudol can significantly reduce the three renal function indicators ( Figure 1 ).

[0076] 2. After the modeling was completed, the mice were fed for 24 hours and then the kidneys were taken out to make paraffin sections. The HE staining results of the paraffin sections were used to observe the effect of the Chinese medicine monomer Hamaudol in alleviating the renal pathological damage caused by IRI.

[0077] The results of HE staining of renal paraffin sections showed that the number of vacuoles in the renal tubules of mice in the IRI group increased compared with that in the Sham group, the lumen of the renal tubules was dilated, and the brush border was shedding, all of which indicated that the degree of renal pathological damage was aggravated;

[0078] In the IRI+Hamaudol group, the number of vacuoles in the renal tubules of mice decreased, the dilation of the renal tubule lumen decreased, and the shedding of the brush border decreased. These results indicate that the degree of renal pathological damage was alleviated.

[0079] This comparison result suggests that the Chinese medicine monomer Hamaudol alleviates the renal pathological damage induced by ischemia-reperfusion ( Figure 2 ).

[0080] 3. After modeling, continue feeding for 24 hours and detect the expression levels of KIM-1 and NGAL gene mRNA in the kidney tissue of mice. Figure 3 shown.

[0081] The results showed that the relative expression of mRNA of acute kidney injury biomarker genes KIM-1 and NGAL genes in the kidneys of mice in different treatment groups was different. The relative expression levels of AKI biomarker genes KIM-1 and NGAL genes in IRI group mice were 204.63±11.54 and 155.23±6.45, respectively. It can be seen that the AKI biomarker genes in IRI group mice were significantly higher than those in Sham group mice (the relative expression levels of KIM-1 and NGAL genes were 1.08±0.10 and 1.04±0.13, respectively).

[0082] The relative expression levels of KIM-1 and NGAL genes in the kidneys of mice in the IRI+Hamaudol group were 108.58±10.37 and 96.13±5.57, respectively. It can be seen that the relative expression levels of AKI biomarker genes KIM-1 and NGAL genes in mice in the IRI+Hamaudol group were significantly downregulated.

[0083] 4. After modeling, the mice were fed for 24 hours and their kidneys were harvested to detect the relative expression levels of inflammation-related genes. Figure 4 shown.

[0084] The results show:

[0085] (1) The relative expression levels of inflammation-related genes IL-1β, IL-6, MCP-1, and COX-2 in acute renal injury in IRI mice were significantly increased, which were 4.12±0.30, 5.55±0.25, 11.10±0.84, and 7.10±0.40, respectively. It can be seen that the inflammation-related genes in IRI mice were significantly higher than those in the sham group (the relative expression levels of IL-1β, IL-6, MCP-1, and COX-2 genes were 1.02±0.04, 1.00±0.06, 1.08±0.05, and 1.00±0.04, respectively).

[0086] The relative expression levels of inflammation-related genes IL-1β, IL-6, MCP-1, and COX-2 in the IRI+Hamaudol group were significantly decreased, which were 1.84±0.09, 2.54±0.23, 3.85±0.29, and 2.29±0.21, respectively; the mRNA expression levels of inflammation-related genes IL-1β, IL-6, MCP-1, and COX-2 in the IRI+Hamaudol group were reduced by 55.28%, 54.23%, 65.34%, and 67.72%, respectively, compared with those in the IRI model group.

[0087] This indicates that the intervention of the Chinese medicine monomer Hamaudol can alleviate kidney inflammation.

[0088] (2) The kidneys of mice were taken and paraffin sections were made. TUNEL apoptosis staining of the kidney paraffin sections showed that the number of apoptotic cells in the kidney tissue of the mice in the IRI group increased compared with the mice in the Sham group, while the number of apoptotic cells in the kidney tissue of the mice in the IRI+Hamaudol group decreased compared with the mice in the IRI group ( Figure 4 B), decreased by 47.03%.

[0089] (3) DHE staining of renal paraffin sections showed that the oxidative damage of renal tissue in the IRI group was aggravated compared with that in the Sham group, while the oxidative damage of renal tissue in the IRI+Hamaudol group was alleviated compared with that in the IRI group ( Figure 4 C), decreased by 53.58%.

[0090] 5. After modeling, continue feeding for 24 hours, take the mouse colon to make paraffin sections, perform immunohistochemical staining, and detect the expression of inflammatory factors. Figure 5 shown.

[0091] The results showed that intervention with the Chinese medicine monomer Hamaudol improved the intestinal barrier damage caused by IRI. After the model was established and the feeding continued for 24 hours, the colon of the mice was taken to make paraffin sections. The results of immunohistochemical staining of the colon paraffin sections showed that the expression level of tight junction protein Occludin in the colon tissue of the IRI group mice (Occludin relative expression level: 0.30±0.02) was significantly reduced compared with the Sham group mice (Occludin expression level: 1.08±0.07), which was reduced by 71.86%;

[0092] The expression level of tight junction protein Occludin in the colon tissue of mice in the IRI+Hamaudol group was significantly increased compared with that in the model group (0.69±0.02) ( Figure 5 A, B in it).

[0093] Compared with the mice in the Sham group (ZO-1 expression level: 1.03±0.06), the expression level of tight junction protein ZO-1 in colon tissue of the mice in the IRI group (ZO-1 expression level: 0.26±0.02) was significantly decreased, by 74.45%;

[0094] The expression level of tight junction protein ZO-1 in colon tissue of mice in IRI+Hamaudol group was significantly increased compared with that in model group (0.71±0.04) ( Figure 5 A, B in it).

[0095] The above comparison results suggest that the Chinese medicine monomer Hamaudol alleviates the intestinal barrier damage in the acute kidney injury mouse model ( Figure 5 C, D).

[0096] The above description is only a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment as above, it is not intended to limit the present invention. Any technical personnel in this field can make some changes or modifications to equivalent embodiments of equivalent changes using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any brief modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention are still within the scope of the technical solution of the present invention. Therefore, the protection scope of the present invention should be based on the definition of the claims.

Claims

1. The use of chelidonol in preparing a drug for treating and / or alleviating acute kidney injury, wherein the chelidonol chemical formula is C 15 H 16 O5, its structural formula is as follows: 。 2. The use according to claim 1, characterized in that: The drug is used for at least one of (a) to (g): (a) Treatment of acute kidney injury; (b) Increased expression of intestinal tight junction proteins induced by acute kidney injury; (c) Reduce serum endotoxin levels caused by acute kidney injury, and downregulate the biochemical indicators of acute kidney injury such as serum creatinine, urea nitrogen, and serum cystatin levels; (d) Down-regulation of the expression levels of KIM-1 and NGAL gene mRNA in the kidneys caused by acute kidney injury; (e) Down-regulate the expression levels of renal inflammatory genes IL-1β, IL-6, MCP-1, and COX-2 caused by acute kidney injury; (f) Improve renal tissue pathology in acute kidney injury; (g) Treatment of acute kidney injury induced by renal ischemia-reperfusion, accompanied by intestinal mucosal damage.

3. The use according to claim 1 or 2, characterized in that: The medicine contains chorilol as an effective ingredient, and also contains a medicine carrier and pharmaceutically acceptable auxiliary materials.

4. The use according to claim 3, characterized in that: The drug carrier includes one or more of fillers, binders, wetting agents, disintegrants, lubricants, and flavoring agents commonly used in medicine.

5. The use according to claim 4, characterized in that: The dosage form of the medicine is tablet, capsule or injection.

6. The use according to claim 4, characterized in that: The dosage form of the drug is dispersible tablet, lozenge, orodisintegrating tablet, sustained-release tablet, soft capsule, dripping pill, granule, powder injection or aerosol.

7. Use of chelidonol in the preparation of a drug for treating and / or alleviating intestinal barrier damage caused by acute renal injury, wherein the chelidonol has a chemical formula of C 15 H 16 O5, its structural formula is as follows: 。 8. The use according to claim 7, characterized in that: The medicine contains chorilol as an effective ingredient, and also contains a medicine carrier and pharmaceutically acceptable auxiliary materials.

9. The use according to claim 8, characterized in that: The drug carrier includes one or more of fillers, binders, wetting agents, disintegrants, lubricants, and flavoring agents commonly used in medicine.

10. The use according to claim 9, characterized in that: The dosage form of the medicine is tablet, capsule or injection.

11. The use according to claim 9, characterized in that: The dosage form of the drug is dispersible tablet, lozenge, orodisintegrating tablet, sustained-release tablet, soft capsule, dripping pill, granule, powder injection or aerosol.

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