Application of Drp1 in preparation of kit and medicine for diagnosing acute kidney injury

Abstract

The invention discloses application of Drp1 in preparation of an acute kidney injury diagnostic kit and medicine, and belongs to the technical field of acute kidney injury. The Drp1 can be used as a biomarker in preparation of an acute kidney injury diagnostic kit, and can also be used as a target in preparation of drugs for screening, preventing or treating acute kidney injury.

Description

Technical Field

[0001] The present application relates to the technical field of acute kidney injury, and in particular, to an application of Drp1 in the preparation of a diagnostic kit and a drug for acute kidney injury. Background Art

[0002] Extracorporeal circulation (CPB)-related acute kidney injury (AKI) is a common and serious complication in pediatric cardiac surgery. Studies have shown that the incidence of extracorporeal circulation-related acute kidney injury (CPB-AKI) is high in pediatric patients, and this high incidence has a significant impact on the patient's postoperative recovery and long-term health. Studies have shown that the occurrence of CPB-AKI significantly increases the need for vasoactive drugs in children after surgery, which may be due to low cardiac output syndrome caused by renal injury. In addition, CPB-AKI will also prolong the mechanical ventilation time and ICU observation time of children, because impaired renal function may lead to fluid retention and respiratory insufficiency, thus requiring longer respiratory support. In order to effectively reduce the incidence of CPB-AKI, strengthening the comprehensive understanding of CPB-AKI in infants and young children, early detection and diagnosis, and taking appropriate intervention measures can better explain and manage the complexity of AKI after pediatric cardiac surgery, thereby improving the overall prognosis of children.

[0003] Based on this, the present application provides an application of Drp1 in the preparation of an acute kidney injury diagnostic kit and a drug. Summary of the invention

[0004] The present application provides an application of Drp1 in the preparation of an acute kidney injury diagnostic kit and a drug to solve the above-mentioned technology.

[0005] This application is implemented as follows: In a first aspect, the present application provides a use of Drp1 as a biomarker in the preparation of an acute kidney injury diagnostic kit, wherein the acute kidney injury diagnostic kit is capable of quantitatively detecting the marker Drp1.

[0006] In a second aspect, the present application provides an application of Drp1 as a target in the preparation and screening of acute kidney injury drugs.

[0007] In a third aspect, the present application provides a use of Drp1 as a target in the preparation of a drug for preventing or treating acute kidney injury.

[0008] The beneficial effects of this application are at least as follows: The inventors of the present application have found through research that Drp1 is highly expressed in the mitochondria in a rat model of acute kidney injury and causes mitochondrial damage. Therefore, Drp1 is an important regulatory factor involved in acute kidney injury. By diagnosing whether the content of Drp1 in the kidney has increased significantly, it can be used as a biomarker to diagnose whether the patient has acute kidney injury. In addition, by inhibiting the high expression of Drp1, acute kidney injury can be alleviated or treated. Drp1 can be used as a target for screening, preventing or treating drugs for acute kidney injury. BRIEF DESCRIPTION OF THE DRAWINGS

[0009] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present application and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without paying creative work.

[0010] Figure 1 This is a test result diagram of serum creatinine value in an embodiment of the present application; Figure 2 The results of HE staining of kidney tissue of each group of rats in the examples of this application are shown; Figure 3 Transmission electron microscopic images of mitochondria of rat renal tubular cells in each group of the examples of the present application; Figure 4 The graphs are the result of changes in mitochondrial membrane potential of renal tubular cells of rats in each group according to the examples of the present application; Figure 5 JC-1 polymers / monomers in rat renal tubular cells in each group of the examples of the present application; Figure 6 Flow cytometry of mitochondrial ROS in rat renal tubular cells of each group in the examples of the present application; Figure 7 This is a graph showing the average fluorescence intensity of MitoSOX in mitochondria of rat renal tubular cells in each group of the examples of the present application; Figure 8 The total Drp1 expression level, mitochondrial Drp1 expression level, and cytoplasmic Drp1 expression level of renal tubular cells of each group of rats in the examples of the present application are shown in the figure; Fig. 9 The immunofluorescence co-localization images of Drp1 and mitochondria in the renal tubular cells of each group of rats in the examples of the present application are shown; Fig.10 This is a diagram showing the co-localization ratio analysis of Drp1 and mitochondria in the renal tubular cells of each group of rats in the examples of the present application. DETAILED DESCRIPTION

[0011] The embodiments of the present application will be described in detail below in conjunction with the examples, but it will be appreciated by those skilled in the art that the following examples are only used to illustrate the present application and should not be considered as limiting the scope of the present application. In the examples, if specific conditions are not specified, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be purchased commercially.

[0012] The following is a specific description of the application of Drp1 in the preparation of an acute kidney injury diagnostic kit and a drug according to the examples of the present application: The present application provides a use of Drp1 as a biomarker in the preparation of an acute kidney injury diagnostic kit, wherein the acute kidney injury diagnostic kit can quantitatively detect the marker Drp1. Exemplarily, the acute kidney injury diagnostic kit can quantitatively detect the marker Drp1 in mitochondria.

[0013] The inventors of the present application have found through research that Drp1 is highly expressed in the mitochondria of a rat model of acute kidney injury and causes mitochondrial damage. Therefore, Drp1 is an important regulatory factor involved in acute kidney injury. By diagnosing whether the content of Drp1 in the kidney has increased significantly, it can be used as a biomarker to diagnose whether the patient has acute kidney injury.

[0014] Herein, the term "biomarker" broadly refers to any detectable compound present in or derived from a sample, such as a protein, peptide, proteoglycan, glycoprotein, lipoprotein, carbohydrate, lipid, nucleic acid (e.g., DNA, such as cDNA or amplified DNA, or RNA, such as mRNA), organic or inorganic chemical, natural or synthetic polymer, small molecule (e.g., metabolite), or a distinguishing molecule or distinguishing fragment of any of the above.

[0015] The present application also provides an application of Drp1 as a target in the preparation and screening of acute kidney injury drugs, and an application of Drp1 as a target in the preparation of drugs for preventing or treating acute kidney injury, wherein the drugs contain a Drp1 inhibitor, and the Drp1 inhibitor can inhibit the expression of Drp1 in mitochondria.

[0016] Drp1 is highly expressed in mitochondria in rat models of acute kidney injury and causes mitochondrial damage. By inhibiting the high expression of Drp1, acute kidney injury can be alleviated or treated. Drp1 can be used as a target for screening, preventing or treating drugs for acute kidney injury. The drugs inhibit mitochondrial damage by inhibiting the expression of Drp1 in mitochondria. Among them, acute kidney injury is kidney injury caused by extracorporeal circulation.

[0017] Exemplarily, the drug is an antibody or antigen-binding fragment thereof to Drp1, that is, an antibody or functional fragment thereof that can specifically bind to Drp1. Optionally, the drug is an injectable preparation or an oral preparation, including but not limited to: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, lozenges, granules, granules, pills, powders, pastes, pills, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, patches, etc.

[0018] Furthermore, the drug has at least one of the following uses: (1) reducing the expansion and cavitation of the interstitial space in renal tissue; (2) reducing the serum or blood creatinine content; (3) reducing the mitochondrial reactive oxygen species in renal tubular cells; and (4) increasing the mitochondrial membrane potential.

[0019] The application of Drp1 in the preparation of an acute kidney injury diagnostic kit and a drug is further described in detail below in conjunction with the examples.

[0020] Example

[0021] 1. Experimental Animals In this study, 12 clean-grade SD (Sprague-Dawley) male rats, 6 weeks old, weighing 150-170 g, were selected. The experimental animals were purchased from the Animal Experiment Center of Chongqing Medical University, and the experimental protocol was approved by the Experimental Animal Welfare Ethics Review Committee of the Children's Hospital Affiliated to Chongqing Medical University (CQCMU-IACUC20240508004). These rats were assigned to a temperature of 22 ° C, humidity of 40%-70%, and a 12-hour light / dark cycle for breeding, adapted to the environment for at least 1 week, and ate rodent standard feed and filtered water at any time. They were fasted for 8 hours before surgery and fasted for 2 hours.

[0022] 2. Experimental Animal Grouping and Surgery Clean-grade SD rats were divided into two groups according to the random number table method: sham operation group (SHAM group) and operation group (CPB group), with 6 rats in each group. After weighing, the rats were intraperitoneally injected with 2% sodium pentobarbital at 50 mg / kg. After anesthesia, they were fixed in a supine position on a surgical operating table with a small animal heating pad. The soles of the rats were clamped with tweezers without any reaction, indicating that the anesthesia effect was acceptable. The glottis of the rats was exposed, and a 20G BD indwelling needle was inserted into the rat's trachea under direct vision through the mouth. The ventilator parameters (tidal volume: 25 ml / kg, inspiration-expiration ratio: 1 / 2, respiratory rate: 80 times / min) were set, and mechanical ventilation was performed for assisted breathing. The right neck of the rat was disinfected, the skin and tissue were separated until the jugular vein was exposed, the tissue around the blood vessel was stripped, and after complete freeing, a 2.5 cm homemade venous catheter was slowly inserted (the catheter was pre-filled with heparin in advance and the tail was sealed with a heparin cap), the catheter was fixed after the suction was unobstructed, and the jugular vein puncture and catheterization were successful. The right inguinal area of ​​the rat was disinfected, and the tissue was separated layer by layer until the femoral artery was exposed. A 24G Y-type intravenous catheter was inserted, and heparin was injected at 400 IU / kg for systemic heparinization. The arterial pressure sensor was connected to the monitor to monitor heart rate, blood pressure, etc. The left femoral artery puncture and catheterization operation was the same as the right side, which was the CPB arterial perfusion pathway.

[0023] 3. Establish extracorporeal circulation A 10ml syringe was used as a blood reservoir. The priming solution consisted of 9ml of fresh blood from rats of the same sex, age, and weight + 1ml of 5% sodium bicarbonate. The blood reservoir was located 20cm below the horizontal plane of the rat's heart. The CPB pipeline was heparinized in advance, connected to the small animal membrane lung and placed on the peristaltic pump. After the pipeline was sealed, the peristaltic pump was turned on to exhaust and preheat. After the rat was successfully punctured and cannulated, the position of the pipeline was adjusted and connected to the extracorporeal circulation device until the circulation was stable. The oxygen device was connected to the small animal membrane oxygenator through a glass rotor flowmeter and then pure oxygen was introduced to start the flow. The flow rate gradually increased from a low speed and stabilized at 100ml / (min•kg). During the operation, the heart rate, blood pressure, and body temperature of the rat were closely observed, and the mean arterial pressure was maintained at about 65mmHg. At the same time, the blood reservoir liquid level was closely observed to ensure that the blood reservoir liquid level was not less than 2ml. After maintaining the flow for 1 hour, the venous drainage tube was clamped, the peristaltic pump was turned off, and the observation was performed for 1 hour. If the rat's vital signs were stable, the operation was considered successful. The SHAM group was operated in the same way as the CPB group except that the patients were not transferred to the ventilator. If persistent hypotension (systolic blood pressure below 40 mmHg) occurred during the operation, the experiment was terminated.

[0024] 4. Experimental results testing (1) Vital signs observation and arterial blood gas analysis Arterial blood was drawn from rats for arterial blood gas analysis before transfer (T0), 30 minutes after transfer (T1), and 1 hour after transfer (T2). Arterial pressure was continuously monitored during the experiment, and heart rate and mean arterial pressure were recorded at the corresponding time points. The body temperature of the rats was maintained at around 37°C using a small animal heating pad during the operation.

[0025] The experimental results showed that the rats in the SHAM group and the CPB group were successfully modeled and the experiment was successfully completed. Their vital signs were stable during the operation, and their arterial blood gases were maintained within the normal range.

[0026] (2) Determination of serum biochemical indicators Blood samples were collected before transfer (T0), 30 minutes after transfer (T1), 1 hour after transfer (T2), 30 minutes after the end of transfer (T3), and 1 hour after the end of transfer (T4). Serum was obtained by centrifugation at 4°C and 3000 rpm for 20 minutes, and serum creatinine was detected using a creatinine detection kit.

[0027] The results of serum creatinine test are as follows: Figure 1 As shown in the figure, according to the AKI diagnostic criteria defined by KDIGO, in the SHAM group, the blood Cr values ​​of rats at the four time points of T1, T2, T3, and T4 did not meet the AKI diagnostic criteria compared with T0 (baseline level), the blood Cr level remained relatively stable, no significant changes were observed, and renal function was not significantly impaired. In the CPB group, although the blood Cr level at T1 increased compared with T0, it did not exceed 50% of the baseline level or increase by more than 26.5umol / L. The blood Cr level showed a gradual increase trend in T2, T3, and T4, and compared with T0 (baseline level), it increased by more than 50%, reaching the AKI diagnostic criteria, and the increase in blood Cr level became more significant over time, and the degree of renal function impairment gradually worsened.

[0028] (3) HE staining of kidney tissue After the experiment, fresh kidneys were taken and immediately fixed in 4% paraformaldehyde for 24 hours. The samples were then dehydrated, embedded, and cut into 4 μm paraffin sections. After HE staining, the pathological morphological changes of renal tissue were observed under an optical microscope.

[0029] The results of HE staining of kidney tissue are as follows Figure 2 As shown in the figure, under the light microscope, the renal tissue structure of rats in the SHAM group was intact, the renal tubules were plump, the structure was clear and complete, the cytoplasm was evenly stained, and there was no obvious edema, necrosis or inflammatory cell infiltration. Compared with the SHAM group, the renal cortical tissue sections of rats in the CPB group showed enlarged renal tissue gaps, disordered arrangement of renal tubular epithelial cells, partial disappearance of brush borders, enlarged intercellular gaps, obvious retraction of cytoplasm, deepened nuclear staining, and partial nuclear shedding, indicating obvious acute injury pathological changes in rat renal tissue.

[0030] (4) Transmission electron microscopy observation of mitochondrial morphology in renal tubular cells Fresh kidneys were obtained after the experiment, and the renal cortex was cut into tissue blocks with a thickness of no more than 4 mm and immersed in arsenate buffer (pH 7.4, 4°C) containing 2.5% glutaraldehyde for 24 h. The tissue was washed three times in 0.13 M phosphate-buffered saline for 10 minutes each time, and then the tissue was fixed with 1% osmium tetroxide (OsO4) at room temperature for 2 hours. The dehydration process involved a series of continuous ethanol concentrations (65%, 70%, 75%, 80% and 95%) for 10 minutes each. The tissue was then immersed in tert-butyl alcohol for 10 minutes and dried in CO2, stained with uranyl acetate or lead citrate, and then gold-coated using an ion sputter coater. Images of the samples were captured and analyzed using a transmission electron microscope.

[0031] The ultrastructure of mitochondria in renal tubular cells of rats in the SHAM and CPB groups was observed by electron microscopy. Figure 3 The results showed that the mitochondria in the SHAM group had normal morphology, regular strip-like structures, and were distributed perpendicular to the basal part. The outer and inner membranes of the mitochondria were intact and continuous, the mitochondrial cristae were closely arranged and clearly shaped, and the matrix was dense and uniform, and in a stable state. Compared with the SHAM group, the mitochondrial structure in the CPB group underwent significant pathological changes. The mitochondria changed from the original regular arrangement to scattered distribution, from the normal strip shape to irregular spherical or ellipsoidal shape, and were obviously swollen. The volume was significantly enlarged, and large areas of cavitation appeared in the matrix. The matrix density was significantly reduced, and the mitochondrial cristae were severely damaged. The original regular arrangement state was changed to a broken and loose flocculent structure. The cristae in some areas even disappeared, and the mitochondrial morphology was severely damaged. This indicates that CPB induces cellular oxidative stress, which leads to severe damage to the integrity and function of mitochondria. This damage may be an important cause of tubular cell dysfunction.

[0032] (5) Flow cytometry to detect mitochondrial membrane potential and reactive oxygen species levels in renal tubular cells After the experiment, fresh kidney tissue was taken and the renal cortex was cut into pieces and placed in a pre-cooled PBS culture dish. The tissue was cut into pieces and then aspirated with a dropper. The tissue on the sieve was continuously ground with a grinding rod. The sieve was continuously flushed with PBS while grinding. The filtrate in the culture dish below the sieve was the filtrate after filtration. After the filtrate was allowed to stand for 5 minutes, it was filtered through a 100-mesh sieve in the same way. The filtrate was centrifuged at 1500 rpm for 5 minutes, the supernatant was discarded, and the precipitate was resuspended with 1 mg / ml type II collagenase and digested for 30 minutes, then the digestion was terminated. Use a pipette to mix well and transfer to an EP tube. Centrifuge at 1500 rpm for 5 min, discard the supernatant, add PBS to resuspend the cell pellet so that the cell concentration is at least 1×106, and add JC-1 mitochondrial membrane potential fluorescent probe detection reagent and MitoSOX Red fluorescent probe detection reagent to the cell suspension according to the manufacturer's instructions. Incubate at 37°C for 30 min and then detect using a flow cytometer. For JC-1 monomer detection, the excitation wavelength is 490 nm and the emission wavelength is 530 nm. For JC-1 polymer detection, the excitation wavelength is 525 nm and the emission wavelength is 590 nm. The excitation wavelength of MitoSOX Red detection is 396 nm and the emission wavelength is 610 nm.

[0033] Flow cytometry was used to analyze the changes in mitochondrial membrane potential of renal tubular cells in the SHAM group and the CPB group. Figure 4 The results showed that the mitochondrial membrane potential of cells in the SHAM group remained at a high level, within the normal range, and no depolarization was observed. The mitochondrial membrane potential of cells in the CPB group decreased significantly, and the depolarization of mitochondria was significantly enhanced (P<0.001, Figure 5 ). This indicates that mitochondria are severely damaged and their normal energy metabolism and function are disrupted.

[0034] Flow cytometry was used to analyze the levels of mitochondrial ROS in renal tubular cells in the SHAM group and the CPB group. Figure 6 The results showed that compared with the SHAM group, the level of intracellular mitochondrial ROS in the CPB group was significantly increased (P<0.0001, Figure 7 ), ROS accumulates in large quantities, the oxidative stress response is significantly enhanced, and mitochondrial function becomes obviously abnormal.

[0035] (6) Western blotting to detect the expression level of Drp1 protein in rat kidney tissue After the experiment, 200 mg of fresh kidney tissue was taken, of which 100 mg was placed in 1 ml tissue lysis buffer (containing 1 ml Lysis buffer, 10 μl PMSF, 1 μl protease inhibitor and 10 μl phosphatase inhibitor), homogenized and centrifuged (4 ° C, 12000g, 10 min), and the supernatant was taken. The protein concentration was determined by BCA kit. The protein solution was mixed with sodium dodecyl sulfate sample buffer in a ratio of 4:1, and then denatured in a metal bath for 10 min. The denatured protein was separated by electrophoresis and transferred to PVDF membrane, blocked with 5% skim milk powder at room temperature for 1 h, washed with TBST 3 times, incubated in Drp1 primary antibody at 4 ° C overnight, and incubated with the corresponding secondary antibody at room temperature for 1 h the next day. After washing the membrane 3 times, it was imaged using the Bio-Rad ChemiDocTM Touch imaging system. The gray value ratio of the target protein to β-actin was measured using Image J software, and the expression of the target protein was relatively quantitatively analyzed. The remaining 100 mg of fresh kidney tissue was used to separate and extract mitochondrial and cytoplasmic proteins using a tissue mitochondrial isolation kit. The kidney tissue was cut into small pieces, and 10 times the volume of pre-cooled mitochondrial isolation reagent A was added. Centrifugation was performed at 1000g and 4°C for 5 minutes, and repeated 10 times. Then the supernatant was centrifuged at 11000g and 4°C for 10 minutes. The supernatant was carefully removed and the precipitate was the separated mitochondria. The supernatant was collected and centrifuged at 12000g and 4°C for 10 minutes, which was the cytoplasmic protein without mitochondria. The concentrations of mitochondrial and cytoplasmic proteins were determined by the BCA method, and the gray value ratios of mitochondria to COX IV and cytoplasm to Tubulin were measured under incubation with Drp1 primary antibody and corresponding secondary antibody to analyze the expression of the target protein.

[0036] Western blot was used to detect the Drp1 content in total protein, cytoplasmic protein, and mitochondrial protein of renal tubular cells in the SHAM group and the CPB group. The results are shown in Figure 8 As shown. There was no significant difference in the expression level of Drp1 between the SHAM group and the CPB group in total protein. The intensity of the protein bands in the two groups was basically the same, and the expression of Drp1 at the overall level was not significantly affected (P>0.05). The cytoplasmic protein was separated from the mitochondrial protein, and the results of further analysis showed that the intensity of the Drp1 band in the cytoplasmic protein of the CPB group was significantly weakened, and the expression level of Drp1 was significantly lower than that of the SHAM group (P<0.0001); in the mitochondrial protein, the intensity of the Drp1 band was enhanced, and the expression level was significantly higher than that of the SHAM group (P<0.0001). It can be seen that under CPB conditions, its distribution in the cytoplasm and mitochondria has shifted. This shows that the oxidative stress response caused by CPB may induce the abnormal transport of Drp1 to mitochondria, aggravate the mitochondrial fission disorder, affect the energy metabolism function of mitochondria, and ultimately lead to the occurrence of CPB-AKI.

[0037] (7) Confocal microscopy to observe the co-localization of Drp1 and mitochondrial immunofluorescence After the experiment, fresh kidney tissue was taken and fixed with 4% paraformaldehyde fixative and incubated at room temperature for 10 minutes. Then, permeabilization was performed, incubated with 0.1% Triton X-100 at room temperature for 10 minutes, and the samples were incubated in 5% goat serum at room temperature for 1 hour. Heat shock protein 60 (HSP60) and Drp1 antibodies were then selected as primary antibodies for mitochondria and Drp1, respectively, and incubated overnight at 4°C. The next day, the tissue was rinsed with PBS three times for 5 minutes each time, and then incubated with the corresponding fluorescent-labeled secondary antibody at room temperature for 1 hour. The fluorescent-labeled samples were rinsed with PBS again, stained with DAPI for 5 minutes and rinsed for the last time, and the images were scanned using a confocal microscope, and the fluorescent images were quantitatively analyzed using Image J software.

[0038] Fig. 9 The results showed that the green fluorescence signal of Drp1 in the SHAM group was mainly concentrated on the luminal surface of the cells, and the red fluorescence signal of mitochondria was scattered around the cell nucleus and was more dense at the base. This distribution of mitochondria was consistent with the electron microscopy results of mitochondria in renal tubular cells in this study. In the CPB group, the green fluorescence signal of Drp1 on the luminal surface of the cells gradually diffused to the red fluorescence area of ​​mitochondria at the base. The overlapping area of ​​the two signals increased significantly, showing a certain degree of staggered distribution in space, and the overall co-localization degree was high. Compared with the distribution of Drp1 in the SHAM group, part of Drp1 in the CPB group moved from the cytoplasm to the mitochondria (P < 0.001, Fig.10 ).

[0039] In summary, Drp1 is highly expressed in the mitochondria of the rat model of acute kidney injury and causes mitochondrial damage. Therefore, Drp1 is an important regulatory factor involved in acute kidney injury. By diagnosing whether the content of Drp1 in the kidney has increased significantly, it can be used as a biomarker to diagnose whether there is acute kidney injury. In addition, by inhibiting the high expression of Drp1, acute kidney injury can be alleviated or treated. Drp1 can be used as a target to screen, prevent or treat drugs for acute kidney injury.

[0040] The above description is only a specific embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. Use of Drp1 as a biomarker in the preparation of a diagnostic kit for acute kidney injury, characterized in that: The acute kidney injury diagnostic kit can quantitatively detect the marker Drp1.

2. The use according to claim 1, characterized in that: The acute kidney injury diagnostic kit can quantitatively detect the marker Drp1 in mitochondria.

3. The use according to claim 1, characterized in that: Acute kidney injury is diagnosed based on the expression of Drp1 in the patient's cytoplasm or mitochondria.

4. Application of Drp1 as a target in the preparation and screening of drugs for acute kidney injury.

5. Use of Drp1 as a target in the preparation of a drug for preventing or treating acute kidney injury, characterized in that: The medicine contains a Drp1 inhibitor, and the Drp1 inhibitor can inhibit the expression of Drp1 in mitochondria.

6. The use according to claim 5, characterized in that: The drug inhibits mitochondrial damage by inhibiting the expression of Drp1 in mitochondria.

7. The use according to claim 5, characterized in that: The drug is an antibody or an antigen-binding fragment thereof against Drp1.

8. The use according to any one of claims 5 to 7, characterized in that: The medicine is an injection preparation or an oral preparation.

9. The use according to any one of claims 5 to 7, characterized in that: The acute kidney injury is kidney injury caused by extracorporeal circulation.

10. The use according to any one of claims 5 to 7, characterized in that: The drug has at least one of the following uses: (1) reducing the expansion and cavitation of the interstitial space in renal tissue; (2) reducing the serum or blood creatinine content; (3) reducing the reactive oxygen species in the mitochondria of renal tubular cells; and (4) increasing the mitochondrial membrane potential.

Images