CN117942332A - Application of carnosol in preparing medicament for treating or relieving cisplatin-induced acute kidney injury - Google Patents
Application of carnosol in preparing medicament for treating or relieving cisplatin-induced acute kidney injury Download PDFInfo
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention discloses an application of carnosol in preparing a medicament for treating or relieving cisplatin-induced acute kidney injury, and the application of carnosol in treating the cisplatin-induced acute kidney injury model of mice can obviously improve the kidney structure and function of the mice with acute kidney injury. Carnosol can relieve cisplatin-induced apoptosis of kidney cells, inflammatory response of kidney tissue and apoptosis of kidney cells. At present, effective medicaments for treating acute kidney injury caused by cisplatin are still lacking clinically, and the invention provides effective clinical medicaments for preventing and treating acute kidney injury caused by cisplatin.
Description
Technical Field
The invention belongs to the technical field of biological medicines, and particularly relates to application of carnosol in treating or preparing a medicament for relieving cisplatin-induced acute kidney injury.
Background
Cisplatin (cis-diamine dichloroplatinum, CISPLATIN, CP) is a broad-spectrum platinum antitumor drug, and is widely used for treating solid cancers such as lung cancer, cervical cancer, head and neck cancer, etc. However, the use of cisplatin is limited by its adverse effects such as nephrotoxicity, cardiotoxicity, ototoxicity, hepatotoxicity, gastrointestinal toxicity and neurotoxicity. After intravenous administration, cisplatin starts to distribute in liver, kidney, intestine and other tissues, and accumulates in a large amount in kidney tissues, and is excreted by glomerular filtration or partial tubular secretion, and is slowly excreted, which is liable to cause acute kidney injury (Acute kidney injury, AKI). A recent study showed that patient AKI after cisplatin treatment had a rate of 38% and was typically characterized by tubular, inflammatory and vascular injury. The molecular mechanism of cisplatin-induced kidney injury is complex, and studies have shown that it is mainly involved in the regulation of cell membrane transporters, the induction of inflammation, oxidative stress, mitochondrial dysfunction, the induction of apoptosis, necrosis, pyro-death and kidney vascular injury. Hydration therapy can reduce the occurrence of cisplatin-induced nephrotoxicity, but kidney injury occurs in about 40% of patients after hydration therapy. At present, no effective medicine is clinically available for preventing or treating the renal toxicity caused by cisplatin. Therefore, based on the research on the mechanism of cisplatin-induced kidney injury, it is important to find or develop a drug suitable for cisplatin combination that both counteracts its deleterious effects and at the same time enables it to exert its powerful anticancer properties. A plurality of traditional Chinese medicine active ingredients of traditional Chinese medicine have proved to have the effect of inhibiting the kidney injury induced by the medicine.
Carnosol (Carnosol, CA, fig. 2B) is the main diterpene of rosemary plants (rosemary). It has phenolic structure part and several biological activities of resisting inflammation, resisting bacteria, resisting oxidation, resisting cancer, etc. However, its effect on slowing down acute kidney injury caused by cisplatin has not been reported.
Disclosure of Invention
The invention aims to overcome the side effect of cisplatin in anti-tumor application, and researches show that carnosol can improve acute kidney injury induced by cisplatin, so that the carnosol can be used for preparing medicines for improving acute kidney injury induced by cisplatin.
In order to achieve the above object, the present invention provides the following solutions: application of carnosol in preparing medicine for treating or relieving acute kidney injury induced by cisplatin is provided.
The carnosol of the invention relieves cisplatin-induced tubular injury.
Carnosol of the present invention inhibits cisplatin-induced increases in creatinine and/or urea nitrogen (serum markers of kidney injury).
The carnosol inhibits the increase of marker proteins KIM1 and/HMGB 1 and/NGAL of cisplatin-induced tubular injury.
The carnosol of the invention relieves cisplatin-induced apoptosis of kidney cells.
The carnosol of the invention relieves cisplatin-induced kidney tissue inflammatory response.
The carnosol disclosed by the invention can relieve cisplatin-induced kidney cell apoptosis.
The second technical scheme of the invention is the application of a pharmaceutical composition in a medicament for treating or relieving cisplatin-induced acute kidney injury, wherein the medicament contains carnosol and/or other pharmaceutically acceptable components.
Further, the pharmaceutical composition is prepared in the form of: oral formulations, injections, tablets, microcapsule formulations, and capsule formulations.
Further, the pharmaceutical composition achieves the effect of improving the acute kidney injury by improving apoptosis of kidney cells.
Further, the pharmaceutical composition achieves the effect of improving the acute kidney injury by improving the kidney inflammatory response.
Further, the pharmaceutical composition achieves the effect of improving the acute kidney injury by improving the apoptosis of kidney cells.
The invention provides application of carnosol in preparing a medicament for relieving renal injury caused by cisplatin. The invention adopts carnosol to intervene in a cisplatin-induced acute kidney injury mouse model, can obviously reduce serum creatinine and urea nitrogen levels of mice, can obviously reduce the levels of tubular injury marker proteins KIM1, HMGB1 and NGAL, and obviously improves cisplatin-induced acute kidney tissue injury. The invention expands the application of carnosol, simultaneously provides a new insight for treating acute kidney injury induced by cisplatin, and has very important practical significance.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments will be briefly described below.
FIG. 1 effect of different concentrations of cisplatin and carnosol on cancer cell viability for 48h treatment: A. h1299 cells, b. HepG2 cells; # P <0.01 compared to Control, P <0.01 compared to CA or CP.
Figure 2 effect of carnosol on pathological changes of kidney tissue in mice: A. experimental protocol of carnosol on cisplatin-induced mouse AKI; B. chemical structure of carnosol; C. hematoxylin-eosin staining (HE) and glycogen (PAS) staining results (x 100 and local x 400) of kidney tissue sections of mice; D. scoring of the mouse kidney tissue section HE results; n=3, P <0.01 compared to Control group or CP group.
FIG. 3 effects of carnosol on Blood Urea Nitrogen (BUN), serum creatinine (SCr) levels in cisplatin-induced acute kidney injury mice; p <0.01 compared to Control group or CP group.
FIG. 4 effect of carnosol on cisplatin-induced AKI mouse kidney tissue KIM1, HMGB1 and NGAL levels: western blot analysis of KIM1 and HMGB1 protein expression in mouse kidney tissues; n=3, P <0.01 compared to Control group or CP group; C. mouse kidney NGAL immunohistochemical staining results (x 400).
Figure 5 effect of carnosol on cisplatin-induced apoptosis of kidney tissue of AKI mice: A. renal tissue TUNEL staining results (×400); western blot analysis of CLEAVED CASPASE-3, CLEAVED CASPASE-8, CLEAVED CASPASE-9 and PARP protein expression in mouse kidney tissues; n is greater than or equal to 3, P <0.01 compared with Control group or CP group; G. mouse kidney caspase-3 immunohistochemical staining results (. Times.400).
Figure 6 effect of carnosol on cisplatin-induced inflammation of kidney tissue in AKI mice: the eilsa method detects changes in TNF- α (a) and IL-1β (B) in cisplatin-induced AKI mouse serum by carnosol; c and D mouse kidney F4/80 (C) and TNF-alpha (D) immunohistochemical staining results (. Times.400); E-H.Western blot analysis of p-p65, NLRP3 and ASC protein expression conditions in kidney tissues of mice; n=4, P <0.01 compared to the Control group; p <0.01, P <0.05 compared to CP group; I. results of mice kidney NLRP3 immunohistochemical staining (. Times.400).
Figure 7 effect of carnosol on cisplatin-induced apoptosis of kidney tissue cells of AKI mice: western blot analysis of GSDMD, pro-caspase-1, clear-caspase-1, material IL-1β and IL-18 protein expression in mouse kidney tissue; n=4, P <0.01 or P <0.05 compared to Control group; p <0.01 or P <0.05 compared to CP group; f and G. Mouse kidney IL-1. Beta. (F) and IL-18 (G) immunohistochemical staining results (. Times.400).
Detailed Description
The present invention will be described in further detail with reference to the following specific examples, which will aid in understanding the present invention, but the scope of the present invention is not limited to the following examples.
Example 1
1. Experimental reagents and materials
1.1 Animals
32 SPF male C57BL/6 mice, 20-22g, 8-10 weeks old, purchased from Henan Seebeck Biotech Co. The experiment was approved by the ethical committee of laboratory animals at the new college of medicine.
1.2 Drugs and Agents
Carnosol, specification: 200mg per bottle, content: more than or equal to 98 percent, and is purchased from Chengdu Mandsite biological Co. Cisplatin, specification: 250mg per bottle, available from Soy Corp reagent Co. Urea nitrogen (blood urea nitrogen, BUN) test boxes, creatinine (serum creatinine, SCr) test boxes, all purchased from the nanjing built biosystems; one-step in situ end labeling (TUNEL) apoptosis detection kit (DAB chromogenic method) available from Wohai Weibull biotechnology Co., ltd; hematoxylin eosin (hematoxylin-eosin staining, HE) staining kit and glycogen PAS staining kit (containing hematoxylin) were all purchased from beijing solibao technologies. NLRP3 primary antibody, IL-1 beta primary antibody and IL-18 primary antibody were purchased from Jiangsu Qingqin biological research center Co., ltd; caspase-1 primary antibody and ASC primary antibody were purchased from Santa Cruz Biotechnology company. GAPDH and NGAL primary antibodies were purchased from beggboaosen biotechnology limited. HMGB1 primary antibody was purchased from shanghai bi yun biotechnology limited. KIM 1 primary antibody was purchased from Shanghai Poisson Bay Biotechnology Co. TNF-alpha, IL-1 beta and IL-6ELISA kits were purchased from Thermo FISHER SCIENTIFIC. Goatanti-mouse IgG-HRP (abs 20039 ss) and Goatanti-rabit IgG-HRP (abs 20040 ss) were purchased from Shanghai Aibisin Biotechnology Co.
2. Experimental method
2.1 Modeling
A single intraperitoneal injection of 20mg/kg cisplatin was performed in mice to establish a kidney injury model.
2.2 Grouping and administration methods for animals
The experimental animals were randomly divided into a control group, a carnosol alone treatment group (15 mg/kg), a model group and a carnosol intervention group (15 mg/kg), 8 animals each. The experimental groups of each dose are injected intraperitoneally according to the preset dose, the control group and the model group are respectively injected with physiological saline of corresponding volumes, 1 time a day, and the modeling time is carried out according to figure 2A.
2.3 Sample collection
After the experiment, the eyeballs of the mice are subjected to blood collection, serum is centrifugally separated, and the mice are preserved at the temperature of minus 20 ℃. Animals were sacrificed under anesthesia, double sided kidneys were dissected, and paraformaldehyde fixed or frozen in liquid nitrogen, respectively.
2.4HE and PAS staining for the observation of renal tissue pathological morphology in mice
After the kidney tissue sample is fixed by paraformaldehyde for 48 hours, the kidney tissue sample is dehydrated by gradient ethanol, embedded in paraffin, sliced and the like, HE (high-performance organic) staining or PAS (polyethylene terephthalate) staining is performed, and the pathological state of the kidney tissue of each group of mice is observed under an optical microscope. The percentage of damaged tubular area in random 5 fields of view was analyzed using a double blind random analysis method under 400 x optical fields of view. 0 point: no obvious tubular injury was seen, 1:: damaged tubular area percentage <20%, 2:: 20% < damaged renal tubule area percent <40%,3 points: 40% < damaged tubular area percentage <60%, 4: 60% < damaged tubular area percentage <80%, 5: the area percentage of the damaged renal tubule is more than or equal to 80 percent.
2.5 Biochemical determination of the content of SCr and BUN
The frozen serum was removed and processed according to the procedures described in the corresponding kit instructions, and the SCr and BUN levels were detected using an enzyme-labeled instrument.
2.6TUNEL staining for observing apoptosis of renal tissue cells in mice
Each set of paraffin sections was taken and manipulated according to the instructions of TUNEL assay kit. TdT enzyme and Biotin-dUTP treatment, then adding horseradish peroxidase (Horse-radish peroxidase, HRP) labeled Streptavidin (Streptavidin-HRP, SA-HRP), finally adding HRP substrate mixed solution (DAB) for color development, dying the nuclei of apoptotic cells into brown yellow, and detecting with a common optical microscope after hematoxylin dying.
2.7 ELISA method for determining TNF-alpha and IL-1 beta content
The frozen serum was removed and processed according to the procedures described in the instructions for the corresponding kit, and levels of TNF-alpha and IL-1. Beta. Were detected using an enzyme-labeled instrument.
2.8 Western blotting method for detecting protein expression level in mouse kidney tissue
Taking kidney tissue specimens, adding 250 mu L of precooled RIPA into each 15mg of tissue in a homogenizer, homogenizing, standing on ice for 30min, centrifuging 10000g at 4 ℃ for 10min, extracting the total protein of the kidney tissue, and quantifying by using a BCA protein concentration measuring kit. Western blot was used to detect the expression level of the relevant protein in mouse kidney tissue and semi-quantitatively analyze the band of interest using Image J software.
2.9 Immunohistochemical detection of protein expression levels in mouse kidney tissue
Taking paraffin sections, baking at 60 ℃ for 2 hours, dewaxing xylene for 15 minutes twice, and sequentially dehydrating the paraffin sections by gradient alcohol for 5 minutes each time. PBS was washed 5min X3 times. Sodium citrate antigen was repaired 5min×3 times and washed 5min×3 times with PBS. 3%H 2O2 block endogenous peroxidase activity for 15min, wash 5min x 3 times with PBS. Membranes were permeabilized with 0.3% Triton X-100 for 15min and washed 5min X3 times with PBS. Serum from primary antibody was added for blocking for 30min. A humidity resistant box was added to a refrigerator at 4deg.C for 12h or overnight. PBS was washed 5min X3 times. Adding a secondary antibody, and incubating for 15min at room temperature; PBS was washed 5min X3 times. DAB was developed in dark, hematoxylin staining solution was counterstained for about 30s, excess hematoxylin was washed off with PBS, and the counterstaining effect was examined under a mirror. Gradient alcohol dehydration, xylene transparency, and gum encapsulation.
2.10CCK-8 experiment
Taking logarithmic growth cells, performing digestion counting, inoculating the cells into a 96-well plate at a rate of 1X 10 4/well, placing the cells into an incubator for culturing for 24 hours, adding carnosol with different concentrations, or adding cisplatin with different concentrations, or combining the two medicines, wherein 6 compound wells are arranged at each concentration, and the final volume of each well is 100 mu L. After placing the incubator for further culturing for 48 hours, 10. Mu.L of CCK-8 solution was added to each well, and the plate was incubated in the incubator for 1.5 hours, and absorbance at 450nm was measured with an enzyme-labeled instrument.
2.11 Statistical treatments
Statistical analysis was performed with SPSS21.0 software. Results are expressed as mean ± standard deviation (mean ± SD). GraphPad 8.0 software was used for mapping. The comparison between groups was checked by One-way analysis of variance (One-way ANOVE). P < 0.05 is statistically significant for the differences.
3. Results
3.1 Effect of carnosol on cisplatin killing cancer cells
Strategies to develop protective drugs for cisplatin nephrotoxicity must take into account the response of cancer cells. The ideal approach should protect kidney cells without affecting or even enhancing the anti-tumor effect of cisplatin. Therefore, firstly, the effect of carnosol on killing H1299 and HepG2 cells by using the combination drug administration of carnosol and cisplatin with different concentrations on the proliferation capacity of non-small cell lung cancer cell line H1299 and liver cancer cell line HepG2 cells for 48 hours is evaluated. The results in fig. 1A show that carnosol gradually decreased in H1299 cell viability with increasing dosing concentration, indicating that carnosol alone inhibited H1299 cell proliferation. After co-administration with cisplatin, there was no difference in proliferation of H1299 cells in the 0.625 μm carnosol+5 μm cisplatin group and in the 5 μm carnosol+40 μm cisplatin group compared to the cisplatin group alone at the corresponding concentrations; whereas the 1.25 μm carnosol+10 μm cisplatin group and the 2.5 μm carnosol+20 μm cisplatin group significantly reduced H1299 cell proliferation compared to the cisplatin or carnosol group alone at the corresponding concentrations (P <0.01, fig. 1A). Also in HepG2 cells, the results of fig. 1B show that carnosol gradually decreased with increasing concentration of drug administration, indicating that carnosol alone inhibited HepG2 cell proliferation. After co-administration of cisplatin, there was no difference in HepG2 cell proliferation in the 5 μm carnosol+5 μm cisplatin group and in the 20 μm carnosol+20 μm cisplatin group compared to the cisplatin group alone at the corresponding concentrations, whereas H1299 cell proliferation was significantly reduced in the 10 μm carnosol+10 μm cisplatin group compared to the cisplatin group alone at the corresponding concentrations (P <0.01, fig. 1B). The results show that carnosol does not affect the efficacy of cisplatin, and even at certain concentrations, the sensitivity of cancer cells to cisplatin can be improved, and the anticancer activity of cisplatin can be enhanced.
3.2 Salvianolic improving renal injury and renal function in cisplatin-induced acute renal injury model
To assess the effect of carnosol on cisplatin-induced acute kidney injury, we constructed a mouse AKI model. The specific experimental scheme of the animal experiment is shown in figure 2A. FIG. 2C shows that the cytoplasm was pale red and the nucleus was blue-black after HE staining. The control group can see that the tubular wall of the kidney tubular of the mouse is in a filling state, the cell outline is clear, and the nucleus is complete. Compared with a control group, the mice treated with carnosol alone have compact and complete tissue structure and intact tissue morphology, no obvious damage is found, a model group can see that a large number of tubular epithelial cells have obvious vacuolation, brush-like edges disappear, part of tubular epithelial cells fall off, and a protein-like tube is visible in a cavity; compared with the model group, the vacuolation degeneration of the tubular epithelial cells of the rat kidney of the carnosol intervention group, the disappearance of brush border, the shedding of part of tubular epithelial cells and the reduction of the tubular protein in the lumen are all reduced. Also, the same results appear after PAS staining. Further histological scoring of the kidney tissue HE pictures (fig. 2D), the model group had significantly increased kidney injury scores (P < 0.01) compared to the normal control group; the kidney injury score was significantly reduced (P < 0.01) in the carnosol-interfered group compared to the cisplatin model group, whereas the carnosol alone-treated group was not different from the control group. These results suggest that carnosol can alleviate cisplatin-induced tubular injury.
Urea Nitrogen (BUN) and creatinine (SCr) in serum are major indicators of kidney injury. To evaluate the role of carnosol in protecting cisplatin-induced acute kidney injury, the present invention examined BUN and SCr levels in mouse serum. Compared with the control group, the serum BUN and SCr levels of the mice in the model group are all obviously increased (P is less than 0.01); compared with the model group, the serum BUN and SCr of the mouse of the carnosol intervention group are obviously reduced (P is less than 0.01); whereas the serum BUN and SCr levels of mice were not significantly altered in the carnosol alone group compared to the control group, see figure 3.
In order to further evaluate the effect of carnosol on cisplatin-induced tubular injury, the invention detects changes in the marker proteins KIM1, HMGB1 and NGAL of tubular injury by using western blot and IHC methods. Western blot results showed that the expression levels of KIM1 and HMGB1 were significantly increased in the kidney tissue of mice in the model group compared to the control group (P <0.01, FIGS. 4A and 4B), and that the expression levels of these proteins were not significantly altered in the kidney tissue of mice in the treatment group with carnosol alone. Compared to the model group, the expression levels of these proteins were significantly down-regulated in kidney tissue of mice from the carnosol-intervention group (P <0.01, fig. 4A and 4B). The results of kidney immunohistochemistry showed positive brown expression. Compared with the control group, the expression of the mouse kidney tissue NGAL of the model group is obviously increased, while the expression of the mouse kidney tissue NGAL of the carnosol dry prognosis is obviously reduced, and the expression of the mouse kidney tissue NGAL of the single group treated with the carnosol has no obvious effect (fig. 4C). This result suggests that carnosol can reduce cisplatin-induced tubular injury.
These results demonstrate that carnosol protects the kidney of cisplatin-induced AKI mice.
3.3 Effect of carnosol on apoptosis of acute kidney injury mice kidney caused by cisplatin
TUNEL staining showed that nuclei were brown-yellow and apoptotic cells (fig. 5A). Compared with the control group, the kidney tissue of the model group mice can be seen to have a large number of apoptosis positive cells, while the independent treatment group of carnosol is not different from the control group; compared with the model group, the apoptosis positive cells of mice in the carnosol intervention group are obviously reduced, which indicates that carnosol can inhibit cisplatin-induced apoptosis of kidney tissue cells of AKI mice (figure 5A). Western blot results showed that the expression levels of mouse kidney tissue CLEAVED CASPASE-3, CLEAVED CASPASE-8, CLEAVED CASPASE-9 and PARP were significantly increased in the model group compared to the control group (P <0.01, FIG. 5B-F), whereas the rat kidney tissue alone treated with carnosol did not significantly alter the expression levels of these proteins (FIG. 5B-F). Compared to the model group, the expression levels of carnosol-interfered group mice kidney tissues CLEAVED CASPASE-3, CLEAVED CASPASE-8, CLEAVED CASPASE-9 and PARP were significantly down-regulated (P <0.01, FIG. 5B-F). The results of kidney immunohistochemistry showed that brown color was positive for caspase-3 expression (FIG. 5G). Compared with a control group, the expression of the mouse kidney tissue caspase-3 in the model group is obviously increased, the expression of the mouse kidney tissue caspase-3 is obviously reduced after the dry reaction of the carnosol, and the expression of the mouse kidney tissue caspase-3 in the single group treated by the carnosol has no obvious influence, which is consistent with the Western blot determination result. These results indicate that after cisplatin molding, apoptosis of mouse kidney cells is promoted, and carnosol can significantly improve cisplatin-induced AKI by inhibiting apoptosis.
3.4 Effect of carnosol on cisplatin-induced acute kidney injury mouse kidney tissue inflammation
To evaluate whether carnosol can attenuate cisplatin-induced inflammation, this study examined the effects of carnosol on cisplatin-induced inflammatory factors and macrophages in serum and kidney tissues of AKI mice. As shown in FIGS. 6A-6D, the expression levels of TNF-. Alpha.and IL-1β in serum were elevated in the model group and kidney tissue, while F4/80 positive cells (macrophages) were increased in the kidney tissue, as compared to the control group. The carnosol intervention can inhibit the production of these inflammatory factors and macrophages, which are not significantly altered by treatment with carnosol alone. TNF- α and IL-1β are regulated by NF- κB/NLRP3 signaling pathways. To further investigate the mechanism of inflammation caused by carnosol on cisplatin, we examined the effect of carnosol on the cisplatin-induced renal tissue NF- κB/NLRP3 signaling pathway in kidney-injured mice. Western blot results showed that the expression levels of P-P65, NLRP3 and ASC were significantly increased in the kidney tissue of mice in the model group compared to the control group (P <0.01, FIG. 6E), whereas the kidney tissue of mice in the group treated with carnosol alone did not significantly change the expression levels of these proteins (FIG. 6E). Compared to the model group, the kidney tissue of the carnosol-interfered group mice significantly down-regulated the expression levels of these proteins (P <0.01 or P <0.05, fig. 6E). These results indicate that carnosol protects cisplatin-induced renal inflammatory response by inhibiting NF- κb/NLRP3 signaling pathway.
3.5 Effect of carnosol on cisplatin-induced apoptosis of kidney tissue cells of AKI mice
Studies have shown that NLRP3-caspase-1 inflammatory pathway mediated apoptosis plays an important role in kidney injury. In order to investigate the effect of carnosol on cisplatin-induced apoptosis of kidney tissue, the present invention examined protein associated with apoptosis. Western blot results showed that the expression levels of GSDMD, pro-caspase-1, clear-caspase-1, material IL-1β and IL-18 were significantly increased in the kidney tissue of the mice in the model group compared to the control group (P <0.01 or P <0.05, FIGS. 7A-7E), whereas the expression levels of these proteins were not significantly altered in the kidney tissue of mice in the treatment group with carnosol alone (FIGS. 7A 7A-7E). Compared to the model group, the kidney tissue of the carnosol-interfered group mice had significantly down-regulated expression levels of these proteins (P <0.01 or P <0.05, fig. 7A-7E). The results of kidney immunohistochemistry showed positive expression of IL-1. Beta. Or IL-18 in brown color in FIG. 7F and FIG. 7G. Compared with a control group, the expression of the IL-1 beta and the IL-18 of the kidney tissue of the mice in the model group is obviously increased, the expression of the IL-1 beta and the IL-18 of the kidney tissue of the mice is obviously reduced after the dry treatment of the carnosol, and the expression of the IL-1 beta and the IL-18 of the kidney tissue of the mice in the single group is not obviously influenced by the treatment of the carnosol, which is consistent with the Western blot measurement result. These results indicate that carnosol reduces cisplatin-induced coke death in kidney tissue cells.
The above embodiments are only illustrative of the preferred embodiments of the present invention and are not intended to limit the scope of the present invention, and various modifications and improvements made by those skilled in the art to the technical solutions of the present invention should fall within the protection scope defined by the claims of the present invention without departing from the design spirit of the present invention.
Claims (9)
1. Application of carnosol in preparing medicine for treating or relieving acute kidney injury induced by cisplatin is provided.
2. The use of claim 1, wherein carnosol alleviates cisplatin-induced tubular injury.
3. Use according to claim 1, wherein carnosol inhibits cisplatin-induced increases in creatinine and/or urea nitrogen.
4. The use according to claim 1, wherein carnosol inhibits the elevation of cisplatin-induced tubular injury marker proteins KIM1 and/HMGB 1 and/NGAL.
5. The use of claim 1, wherein carnosol relieves cisplatin-induced apoptosis of kidney cells.
6. The use of claim 1, wherein carnosol relieves cisplatin-induced inflammatory response of kidney tissue.
7. The use of claim 1, wherein carnosol relieves cisplatin-induced kidney cell apoptosis.
8. Use of a pharmaceutical composition in a medicament for the treatment or alleviation of cisplatin-induced acute kidney injury characterized in that the medicament comprises carnosol and/or other pharmaceutically acceptable ingredients.
9. The use according to claim 8, wherein the pharmaceutical composition is prepared in the form of: oral formulations, injections, tablets, microcapsule formulations, and capsule formulations.
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