Application of dihydrotanshinone I in preparation of medicine for relieving cisplatin-induced acute kidney injury

Abstract

The invention relates to the technical field of medicines, in particular to application of dihydrotanshinone I in preparation of a medicine for relieving cisplatin-induced acute kidney injury. Through the target protein TRIM28 of dihydrotanshinone I, which plays a protective role in the acute kidney injury process, a new mechanism for relieving the cisplatin renal toxicity by inhibiting TRIM28-mediated oxidative stress and cell apoptosis pathway is provided for dihydrotanshinone I, and an accurate treatment target and strategy are provided for prevention and treatment of cisplatin renal injury.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, specifically to the application of dihydrotanshinone I in the preparation of drugs to alleviate cisplatin-induced acute kidney injury. Background Technology

[0002] Cisplatin is a widely used platinum-based chemotherapy drug in clinical practice, showing significant efficacy against solid tumors such as ovarian cancer, lung cancer, and bladder cancer. However, its dose-dependent nephrotoxicity severely limits its clinical application—approximately 30% of patients experience acute kidney injury (AKI), manifested as renal tubular necrosis and decreased renal function, often leading to chemotherapy interruption. Current research indicates that the core mechanisms by which cisplatin induces kidney injury include: ① Oxidative stress: Cisplatin induces excessive ROS production in renal tubular epithelial cells, disrupting the oxidative-antioxidant balance; ② Apoptosis: Cisplatin activates the apoptosis signaling pathway, leading to the death of renal tubular epithelial cells. Currently used clinical methods such as hydration therapy and antioxidant adjuvants (such as N-acetylcysteine) have limited effectiveness, and there is a lack of specific drugs targeting the dual mechanisms of "oxidative stress + apoptosis."

[0003] Dihydrotanshinone I (DHT, CAS 87205-99-0) is a natural diterpenoid compound extracted from Tanshinone (Salvia miltiorrhiza) with multiple pharmacological activities, including antioxidant, anti-inflammatory, and antitumor effects. CN202410453043 discloses the application of dihydrotanshinone I, alone or in combination with lenvatinib, in the treatment of liver cancer, demonstrating its ability to inhibit liver cancer cell proliferation and promote apoptosis. This patent focuses on targeted therapy for liver cancer, with tumor cells as the research subject, and does not address the toxic side effects of chemotherapy drugs such as cisplatin, nor is it related to kidney damage repair. CN202410261574 reports the use of dihydrotanshinone I in the treatment of TREX1 gene-related autoinflammatory diseases, confirming that it can alleviate inflammatory responses by inhibiting the cGAS-STING pathway. This patent targets autoinflammatory diseases, with an anti-inflammatory mechanism, and does not address chemotherapy-induced organ damage, nor explore the synergistic regulation of oxidative stress and apoptosis. CN201811173423 discloses the use of dihydrotanshinone I in the preparation of drugs for treating acute kidney injury, confirming its protective effect against lipopolysaccharide (LPS)-induced acute kidney injury. The mechanism involves inhibiting TLR4 dimer formation and downregulating inflammatory factors (TNF-α, IL-6, etc.). While this patent involves kidney injury, the core mechanism of LPS-induced kidney injury is the inflammatory response. It does not reveal the direct regulatory effect of dihydrotanshinone I on oxidative stress or apoptosis pathways, nor does it address the nephrotoxicity of cisplatin, a specific chemotherapeutic drug.

[0004] Therefore, the research and development of dihydrotanshinone I-related drugs with well-defined targets that can simultaneously inhibit oxidative stress and apoptosis is of great significance for solving the problem of cisplatin nephrotoxicity. Summary of the Invention

[0005] To address the problems existing in the prior art, the purpose of this invention is to provide the application of dihydrotanshinone I in the preparation of drugs to alleviate cisplatin-induced acute kidney injury.

[0006] The objective of this invention is achieved through the following technical solution: In a first aspect, the present invention provides the use of dihydrotanshinone I in the preparation of a drug to alleviate cisplatin-induced acute kidney injury.

[0007] Secondly, the present invention provides the use of dihydrotanshinone I in the preparation of a drug that exerts a renal protective effect by targeting the TRIM28 protein-mediated oxidative stress and apoptosis pathway.

[0008] Thirdly, the present invention provides the use of dihydrotanshinone I in the preparation of a medicament for use in combination with cisplatin to reduce its nephrotoxicity.

[0009] Preferably, the structural formula of dihydrotanshinone I is: ; Preferably, the pharmaceutical ingredient includes dihydrotanshinone I, cisplatin or other platinum-based chemotherapy drugs, and a pharmaceutically acceptable carrier.

[0010] Preferably, the dihydrotanshinone I reduces kidney damage by covalently binding to the Cys-232 site of the TRIM28 protein, thereby inhibiting oxidative stress and apoptosis.

[0011] Preferably, the dihydrotanshinone I reduces kidney damage by downregulating the expression of pro-apoptotic proteins BAX and cleaved caspase-3.

[0012] Preferably, the dihydrotanshinone I reduces kidney damage by upregulating the expression of the anti-apoptotic protein Bcl-2.

[0013] Preferably, the dihydrotanshinone I alleviates kidney damage by reducing the levels of kidney injury markers KIM-1 and NGAL.

[0014] Preferably, the drug dosage form is one of injection, granules, tablets, powder, capsules, and pellets.

[0015] Preferably, the dihydrotanshinone I is administered orally or by injection, preferably orally, at a dose of 5-30 mg / kg / day, more preferably 15 mg / kg / day.

[0016] Preferably, the use of the dihydrotanshinone I in the preparation of a medicament for use in combination with cisplatin to reduce its nephrotoxicity is indicated by oral administration of the dihydrotanshinone I starting 7 days before cisplatin chemotherapy (15 mg / kg / day) and continuing until 72 hours after the end of chemotherapy.

[0017] Preferably, the drug is suitable for cancer patients receiving platinum-based chemotherapy, and has important clinical value, especially for patients with ovarian cancer, lung cancer, and other cancers treated with high-dose cisplatin regimens.

[0018] The beneficial effects of this invention are as follows: 1. This invention provides the target protein TRIM28, which plays a protective role of dihydrotanshinone I in acute kidney injury. It proposes a new mechanism by which dihydrotanshinone I alleviates cisplatin nephrotoxicity by inhibiting TRIM28-mediated oxidative stress and apoptosis pathways, providing a precise therapeutic target and strategy for the prevention and treatment of cisplatin-induced kidney injury.

[0019] 2. This invention prepares a combination therapy of dihydrotanshinone I and cisplatin, which significantly reduces the nephrotoxicity of cisplatin while ensuring its anti-tumor efficacy. It solves the key technical problem of "maintaining efficacy and reducing toxicity" in clinical chemotherapy and has important clinical application value.

[0020] 3. The preparation process of the dihydrotanshinone I pharmaceutical composition provided by the present invention is simple, and dihydrotanshinone I, as a natural product, has the characteristics of low toxicity and high efficiency, which can significantly reduce the risk of toxic side effects during treatment, and has significant clinical application advantages and industrialization prospects. Attached Figure Description

[0021] The present invention will be further described with reference to the accompanying drawings, but the embodiments in the drawings do not constitute any limitation on the present invention. For those skilled in the art, other drawings can be obtained based on the following drawings without creative effort.

[0022] Figure 1 The chemical structural formula of dihydrotanshinone I in this embodiment of the invention is shown below.

[0023] Figure 2 This is a schematic diagram of the effect of dihydrotanshinone I on cisplatin-induced cytotoxicity in an embodiment of the present invention; wherein, (a) is a graph of HK-2 cell viability detection after 24 hours of treatment with cisplatin and different concentrations of dihydrotanshinone I; (b) is a quantitative analysis of ROS fluorescence intensity based on flow cytometry data.

[0024] Figure 3This is a schematic diagram of the verification experiment of the target of dihydrotanshinone I in the embodiment of the present invention; wherein, (a) is the immunofluorescence experiment of HK-2 cells, (b) is the pull-down experiment (dihydrotanshinone I and HK-2 cells), (c) is the in-gel fluorescence experiment, and (d) is the molecular docking analysis of DHT and TRIM28.

[0025] Figure 4 This is a schematic diagram of a proteomics experiment according to an embodiment of the present invention; wherein, (a) is a comparison diagram of differentially expressed proteins, and (b) is an enrichment analysis of differentially expressed proteins in the KEGG and GO pathways.

[0026] Figure 5 This is a schematic diagram of the in vitro verification experiment of dihydrotanshinone I in the embodiments of the present invention; wherein, (a) is the immunofluorescence image of HK-2 cells under different treatment conditions, (b) is the effect of dihydrotanshinone I and the antioxidant NAC on the viability of HK-2 cells treated with cisplatin, and (c) is the effect of dihydrotanshinone I and the apoptosis inhibitor Z-VAD-FMK on the viability of HK-2 cells treated with cisplatin.

[0027] Figure 6 This is a schematic diagram of the experiment verifying the protective effect of dihydrotanshinone I on the kidney in an embodiment of the present invention; wherein, (a) shows the mouse body weight and renal function indicators (CREA and BUN) under different treatment conditions, and (b) shows the Western blot analysis of apoptosis and renal injury markers (cleaved caspase-3, BAX, Bcl-2, KIM-1 and NGAL) with β-actin as an internal control. Detailed Implementation

[0028] The technical solution of the present invention is illustrated below through specific examples. It should be understood that the one or more method steps mentioned in the present invention do not preclude the existence of other method steps before or after the combined steps, or the insertion of other method steps between these explicitly mentioned steps; it should also be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the present invention. Furthermore, unless otherwise stated, the numbering of each method step is merely a convenient tool for identifying each method step, and not for limiting the order of the method steps or defining the scope of the present invention. Changes or adjustments to their relative relationships, without substantially altering the technical content, should also be considered within the scope of the present invention.

[0029] To better understand the above technical solutions, exemplary embodiments of the present invention are described in more detail below. While exemplary embodiments of the present invention are shown, it should be understood that the present invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided to enable a more thorough understanding of the present invention and to fully convey the scope of the invention to those skilled in the art.

[0030] The present invention will be further described below with reference to the following embodiments.

[0031] In a first aspect, embodiments of the present invention provide the application of dihydrotanshinone I in the preparation of a drug to alleviate cisplatin-induced acute kidney injury.

[0032] The structural formula of dihydrotanshinone I is as follows: Figure 1 As shown: ; Preferably, the pharmaceutical ingredient includes dihydrotanshinone I, cisplatin or other platinum-based chemotherapy drugs, and a pharmaceutically acceptable carrier.

[0033] Preferably, the dihydrotanshinone I reduces kidney damage by covalently binding to the Cys-232 site of the TRIM28 protein, thereby inhibiting oxidative stress and apoptosis.

[0034] Preferably, the dihydrotanshinone I reduces kidney damage by downregulating the expression of pro-apoptotic proteins BAX and cleaved caspase-3.

[0035] Preferably, the dihydrotanshinone I reduces kidney damage by upregulating the expression of the anti-apoptotic protein Bcl-2.

[0036] Preferably, the dihydrotanshinone I alleviates kidney damage by reducing the levels of kidney injury markers KIM-1 and NGAL.

[0037] Preferably, the drug dosage form is one of injection, granules, tablets, powder, capsules, and pellets.

[0038] Preferably, the dihydrotanshinone I is administered orally or by injection, preferably orally, at a dose of 5-30 mg / kg / day, more preferably 15 mg / kg / day.

[0039] Preferably, the use of the dihydrotanshinone I in the preparation of a medicament for use in combination with cisplatin to reduce its nephrotoxicity is indicated by oral administration of the dihydrotanshinone I starting 7 days before cisplatin chemotherapy (15 mg / kg / day) and continuing until 72 hours after the end of chemotherapy.

[0040] Secondly, the present invention provides the use of dihydrotanshinone I in the preparation of a drug that exerts a renal protective effect by targeting the TRIM28 protein-mediated oxidative stress and apoptosis pathway.

[0041] Thirdly, the present invention provides the use of dihydrotanshinone I in the preparation of a medicament for use in combination with cisplatin to reduce its nephrotoxicity.

[0042] Experimental materials and methods used in this invention application I. Reagents and Materials Reagents: Dihydrotanshinone I (DHT, HY-N0360, MedChemExpress); Cisplatin (Sigma, P4394); Human proximal renal tubular epithelial cells (HK-2 cells, ATCC® CRL-2190™); DMEM medium (Dulbecco's Modified Eagle's Medium, Gibco); Fetal bovine serum (FBS, Gibco); Penicillin-streptomycin mixture (Beyotime); IAA-alkyne probe (Click Chemistry Tools, 1067); TAMRA-azide conjugate (Click Chemistry Tools, 1348); Rabbit anti-TRIM28 antibody (Proteintech, 15202-1-AP); Horseradish peroxidase (HRP)-labeled secondary antibody (CST); BCA protein quantification kit (Beyotime); SDS-PAGE Gel preparation kit (Bio-Rad); mass spectrometry detection reagents (Thermo Fisher Scientific).

[0043] Cells: Human proximal renal tubular epithelial cells (HK-2 cells, ATCC® CRL-2190™).

[0044] Animals: 8-week-old male C57BL / 6 mice (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were housed in an SPF-grade environment (12-hour light-dark cycle, 22±1℃, free access to food and water). All animal experiments were approved by the Ethics Committee of Capital Medical University (approval number AEEI-2022-200).

[0045] II. Experimental Methods The methods used in the embodiments of this invention, such as active proteomics mapping analysis (ABPP), immunofluorescence colocalization, pull-down, Western blot, and mass spectrometry (LC-MS / MS), are all conventional techniques in the field.

[0046] The following detailed description is based on several specific embodiments.

[0047] Example 1 This invention provides the application of dihydrotanshinone I in the preparation of drugs to alleviate cisplatin-induced acute kidney injury, specifically by inhibiting cisplatin-induced HK-2 cell damage through dihydrotanshinone I, including: Experimental objective: To verify the protective effect of dihydrotanshinone I against cisplatin-induced HK-2 cell cytotoxicity.

[0048] HK-2 cells were cultured in DMEM medium containing 10% FBS and 1% penicillin-streptomycin at 37°C in a 5% CO2 incubator (passaged when confluence reached 80%-90%). Cells were cultured at 5 × 10⁻⁶ cells / year. 3 Cells were seeded in 96-well plates and allowed to adhere overnight. After overnight adhesion, cells were divided into four groups: control (CON, medium containing 0.1% DMSO), cisplatin group (CIS, 10 μM cisplatin), low-dose dihydrotanshinone I + cisplatin group (DHT50 ​​+ CIS, 50 μM dihydrotanshinone I pretreated for 2 h followed by 10 μM cisplatin), and high-dose dihydrotanshinone I + cisplatin group (DHT200 + CIS, 200 μM dihydrotanshinone I pretreated for 2 h followed by 10 μM cisplatin). After 24 h of treatment, cell viability was calculated using the CCK-8 assay at 450 nm, apoptosis was detected using Annexin V-FITC / PI double staining, and ROS levels were detected using the DCFH-DA probe.

[0049] The results show that ( Figure 2 Cisplatin treatment significantly reduced cell viability, leading to shrinkage and cell shedding, ROS accumulation, and increased apoptosis. Pretreatment with dihydrotanshinone I improved these indicators with increasing dihydrotanshinone I concentration, with the highest concentration showing the most significant effect. This indicates that dihydrotanshinone I has a significant protective effect against cisplatin-induced HK-2 cell damage, and this effect increases with dosage.

[0050] Example 2 This invention provides the use of dihydrotanshinone I in the preparation of drugs that exert renal protective effects by targeting the TRIM28 protein-mediated oxidative stress and apoptosis pathways. Specifically, it identifies and validates the direct target of dihydrotanshinone I based on ABPP technology.

[0051] Experimental Objective: To screen for the direct molecular targets of dihydrotanshinone I in HK-2 cells using bioproteomics proteomics mapping (ABPP) and to validate these targets through various experiments, including: After HK-2 cells were cultured to the logarithmic growth phase, they were divided into a control group (DMSO treatment) and a dihydrotanshinone I treatment group (20 μM, 40 μM, and 80 μM dihydrotanshinone I pretreatment for 1 h). Cell lysates were collected and incubated with an IAA-alkynyl probe at 37 °C for 1 h, followed by binding to a TAMRA-azide conjugate via a Cu(I)-catalyzed click chemistry reaction. After protein separation by 12% SDS-PAGE, fluorescence signals were detected using an Azure Sapphire RGB NIR scanner, and bands with decreased fluorescence intensity in the two groups of gels were compared. Differential bands were excised, digested with trypsin, and analyzed by LC-MS / MS to identify the proteins. Immunofluorescence colocalization experiments were then performed. HK-2 cells were pretreated with dihydrotanshinone I (40 μM) for 1 h, then labeled with an IAA probe, fixed, and incubated overnight with rabbit anti-TRIM28 antibody, followed by 2 h of incubation with fluorescent secondary antibody. Hoechst staining was performed on the nuclei, and the colocalization of TRIM28 and the IAA probe was observed using a confocal microscope. The Pearson coefficient was calculated. Simultaneously, pull-down experiments were performed. HK-2 cell lysates were pretreated with dihydrotanshinone I (0 μM, 20 μM, 40 μM), labeled with an IAA probe, and bound to agarose beads. The bound protein was eluted, and the TRIM28 content was detected by Western blot. The experiment was repeated using purified recombinant TRIM28 protein. Finally, molecular docking was performed. The 3D structure of dihydrotanshinone I was obtained from the SciFinder database, and the crystal structure of TRIM28 (PDB ID: 8CR0) was downloaded from the RCSBPDB database. Preprocessing was performed using AutoDock Tools, and molecular docking was conducted using AutoDock Vina. The binding sites and interactions were visualized using PyMOL.

[0052] The results show that ( Figure 3 In the dihydrotanshinone I treatment group, the fluorescence intensity of the protein band with a molecular weight of approximately 100 kDa decreased with increasing concentration, and it was identified as TRIM28 by LC-MS / MS. Immunofluorescence, pull-down, and molecular docking all confirmed that dihydrotanshinone I directly binds to TRIM28, indicating that TRIM28 is the direct molecular target of dihydrotanshinone I.

[0053] Example 3 This invention provides the use of dihydrotanshinone I in the preparation of drugs for use in combination with cisplatin to reduce its nephrotoxicity, specifically by utilizing dihydrotanshinone I to affect the expression of proteins in cisplatin-induced oxidative stress and apoptosis-related pathways in cisplatin-induced HK-2 cells, including: Experimental objective: To verify the regulatory effect of dihydrotanshinone I on the expression of proteins in cisplatin-induced oxidative stress and apoptosis-related pathways in HK-2 cells.

[0054] HK-2 cells were used at 1×106 Cells were seeded in 6-well plates and allowed to adhere overnight. Cells were then divided into a control group, a cisplatin group (10 μM cisplatin), and a dihydrotanshinone I + cisplatin group (pretreated with 100 μM dihydrotanshinone I for 2 h followed by 10 μM cisplatin). Cells were collected after 24 h of treatment, lysed, and total protein was extracted and quantified using the BCA method. Western blot analysis was used to detect the expression levels of oxidative stress-related proteins (SOD, MDA) and apoptosis-related proteins (BAX, Bcl-2, cleaved caspase-3), with β-actin as an internal control. ImageLab software was used for grayscale quantification. Simultaneously, proteomics analysis (LC-MS / MS) was used to detect differentially expressed proteins in the three groups, focusing on changes in pathway proteins related to oxidative stress (e.g., ROS metabolism, antioxidant enzymes) and apoptosis (e.g., apoptosis regulators, caspase family).

[0055] The results show that ( Figure 4 In the cisplatin group, SOD protein expression was decreased, MDA protein expression was increased, and the BAX / Bcl-2 ratio and cleaved caspase-3 expression were elevated. Further proteomic analysis showed that dihydrotanshinone I could reverse the abnormal expression of key proteins in cisplatin-induced oxidative stress pathways (such as NADPH oxidase and glutathione metabolism) and apoptosis pathways (such as mitochondrial apoptosis pathway and death receptor pathway). This indicates that dihydrotanshinone I can regulate the expression of proteins in cisplatin-induced oxidative stress and apoptosis-related pathways.

[0056] Example 4 In vitro validation was conducted to demonstrate that dihydrotanshinone I inhibited cisplatin-induced oxidative stress and apoptosis in HK-2 cells via TRIM28.

[0057] Experimental objective: To verify in vitro that dihydrotanshinone I reduces cisplatin-induced oxidative stress and apoptosis in HK-2 cells by targeting TRIM28.

[0058] HK-2 cells were used at 1×10 5 / wells were seeded in 24-well plates and divided into control group, cisplatin group (10 μM), cisplatin + dihydrotanshinone I group (100 μM dihydrotanshinone I pretreatment + 10 μM cisplatin), and cisplatin + dihydrotanshinone I group (100 μM dihydrotanshinone I pretreatment + 10 μM cisplatin). After 24 h of treatment, ROS levels were quantified by flow cytometry after incubation with a DCFH-DA probe (10 μM) for 30 min; apoptosis rate was detected by flow cytometry after Annexin V-FITC / PI staining; and the expression changes of TRIM28 and oxidative stress and apoptosis-related proteins in Example 3 were detected by Western blot.

[0059] The results show that ( Figure 5Dihydrotanshinone I significantly reduced cisplatin-induced ROS accumulation and apoptosis; after TRIM28 siRNA transfection, the protective effect of dihydrotanshinone I was reversed, indicating that dihydrotanshinone I inhibited cisplatin-induced oxidative stress and apoptosis by targeting TRIM28.

[0060] Example 5 To verify the effect of dihydrotanshinone I in alleviating cisplatin-induced acute kidney injury in mice.

[0061] Experimental objective: To verify the protective effect and mechanism of dihydrotanshinone I against cisplatin-induced acute kidney injury in vivo.

[0062] C57BL / 6 mice were randomly divided into three groups: a control group (CON, intragastric administration of normal saline for 7 days + intraperitoneal injection of normal saline), a cisplatin group (CIS, intragastric administration of normal saline for 7 days + intraperitoneal injection of cisplatin 20 mg / kg), and a dihydrotanshinone I pretreatment group (dihydrotanshinone I + CIS, intragastric administration of dihydrotanshinone I 15 mg / kg / day for 7 days + intraperitoneal injection of cisplatin 20 mg / kg), with 6 mice in each group. 72 hours after cisplatin injection, serum CREA and BUN levels were measured; kidney HE staining was performed to assess renal tubular damage; and SOD activity, MDA content, and the expression of TRIM28, oxidative stress, and apoptosis-related proteins in renal tissue were measured.

[0063] The results show that ( Figure 6 In the cisplatin group, the renal function (CREA, BUN) of mice decreased, the renal tissue pathological damage was obvious, and the related molecular indicators were abnormal. Pretreatment with dihydrotanshinone I could significantly improve the above indicators, indicating that dihydrotanshinone I can alleviate cisplatin-induced acute kidney injury in vivo through TRIM28.

[0064] The experiments in the above embodiments of the present invention can confirm that dihydrotanshinone I is identified by ABPP technology as directly targeting TRIM28. It can inhibit cisplatin-induced HK-2 cell damage and acute kidney injury in mice by regulating the expression of proteins in oxidative stress and apoptosis-related pathways. It is a nephroprotective adjuvant for platinum-based chemotherapy and can be further prepared into specific drugs, including: drug combinations that can be formed by combining it with cisplatin, drug combinations formed by combining it with salvianolic acid A and cryptotanshinone, and drug combinations formed with medium-chain triglycerides (oil phase), polyoxyethylene hydrogenated castor oil (emulsifier), and PEG400 (co-emulsifier), etc.

[0065] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the invention. The illustrative expressions of the above terms in this specification should not be construed as necessarily referring to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. In addition, those skilled in the art can combine and integrate the different embodiments or examples described in this specification.

[0066] Although embodiments of the present invention have been shown and described above, it is understood that the above embodiments are exemplary and should not be construed as limiting the present invention. Those skilled in the art can make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention.

Claims

1. Application of dihydrotanshinone I in the preparation of drugs to alleviate cisplatin-induced acute kidney injury.

2. The use of dihydrotanshinone I according to claim 1 in the preparation of drugs to alleviate cisplatin-induced acute kidney injury, characterized in that, The structural formula of dihydrotanshinone I is: 。 3. The use of dihydrotanshinone I according to claim 1 in the preparation of drugs to alleviate cisplatin-induced acute kidney injury, characterized in that, The drug components include dihydrotanshinone I, cisplatin or other platinum-based chemotherapy drugs, and a pharmaceutically acceptable carrier.

4. The use of dihydrotanshinone I according to claim 1 in the preparation of drugs to alleviate cisplatin-induced acute kidney injury, characterized in that, The drug dosage form is one of the following: injection, granules, tablets, powder, capsules, and pills.

5. The use of dihydrotanshinone I according to claim 1 in the preparation of drugs to alleviate cisplatin-induced acute kidney injury, characterized in that, The dihydrotanshinone I is administered orally or by injection at a dose of 5-30 mg / kg / day.

6. Use of dihydrotanshinone I in the preparation of drugs that exert renal protective effects by targeting the TRIM28 protein-mediated oxidative stress and apoptosis pathway.

7. Use of dihydrotanshinone I in the preparation of a medicament for use in combination with cisplatin to reduce its nephrotoxicity.

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