Objective:The effect of small molecule Sigma-1 receptor on cisplatin(CDDP)-induced acute kidney injury(AKI)was investigated based on mitochondrial dynamic pathway changes.Methods:The experiment was divided into 4 groups,in-cluding control group,PRE-084 group,CDDP group and CDDP+PRE-084 group,with 10 mice in each group.The CDDP group and CDDP+PRE-084 group were intraperitoneally injected with CDDP(15 mg/kg)to induce AKI model,then PRE-084 group and CDDP+PRE-084 group were intraperitoneally injected with PRE-084(0.6 mg/kg)once a day for 7 days.After the end,the levels of serum urea nitrogen(BUN)and serum creatinine(Scr)were detected by automatic biochemical analyzer,the content of re-nal damage molecule 1(KIM-1)in urine was determined by enzyme-linked immunosorbent assay(ELISA),hematoxylin-eosin(HE)staining was used to observe the pathological changes of kidney tissue,Tdt-mediated dUTP notch end labeling(TUNEL)was used to detect cell apoptosis in the kidney,transmission electron microscope was used to observe the ultrastructure of mitochondria in kidney tissue,bioluminescence techniques were used to detect adenosine triphosphate(ATP)production levels in kidney tissue,im-munofluorescence double staining was performed to determine the localization expression of Sigma-1 receptor and Mfn2 in kidney tis-sue,western blot was used to determine the expression of mitochondrial fission proteins Drp1 and Fis1 and mitochondrial fusion pro-teins Opa1 and Mfn1 in renal tissues.Results:Compared with CDDP group,the serum BUN,Scr and urine KIM-1 levels of mice in CDDP+PRE-084 group were decreased(P<0.05),the pathological injury of kidney tissue was significantly improved,the rate of TUNEL positive cells was decreased(P<0.05),the degree of mitochondrial swelling,breakage and vacuole degeneration was re-duced,and the morphology was recovered.ATP content was increased(P<0.05),Sigma-1 receptor and Mfn2 fluorescence stai-ning were enhanced,the relative expressions of Drp1 and Fis1 proteins were down-regulated and the relative expressions of Opa1 and Mfn1 proteins were up-regulated(P<0.05).Conclusion:Mitochondrial division and fusion pathways mediate the development of CDDP-induced AKI in mice,and Sigma-1 receptor plays a protective role in AKI mice by regulating mitochondrial dynamics.
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