CDDO-me缓解阿霉素诱导肾小球足细胞损伤

CDDO-me ameliorated adriamycin-induced kidney podocyte injury

目的探究Nrf2激动剂CDDO-me是否能缓解阿霉素诱导肾小球足细胞损伤。方法 30只8~12周雄性Balb/c小鼠随机分5组:对照组、CDDO-me组、阿霉素组(ADR)、阿霉素+CDDO-me组、阿霉素+奥美沙坦阳性对照组。测定小鼠尿蛋白/肌酐比值,PAS染色观察肾脏病理改变,免疫荧光检测足细胞标志蛋白WT-1,Nephrin的表达水平来观察各组间小鼠肾脏足细胞损伤情况以及CDDO-me对肾脏的保护作用,应用免疫印记对肾组织WT-1与Nephrin进行定量分析。结果与正常对照组相比,ADR组尿蛋白/肌酐比值显著升高,PAS染色发现肾小球系膜基质及系膜增生,部分足细胞脱落,球囊黏连,荧光可见足细胞标志蛋白表达下降.与阿霉素组相比,阿霉素+CDDO-me组小鼠尿蛋白/肌酐比值下降,足细胞脱落减少,肾脏损伤减轻。结论 CDDO-me保护阿霉素诱导肾脏损伤。

Objective To investigate whether Nrf2 agonist CDDO-me can protect glomerular podocyte injury induced by doxorubicin.Methods Thirty 8-12 weeks old male Balb/c mice were randomly divided into 5 groups:control,CDDO-me,Adriamycin(ADR),ADR+CDDO-me,ADR+angiotensin II receptor blocker(ARB)group as a positive control.The urinary protein/creatinine ratio(PCR)was measured.The renal pathological changes were observed by PAS staining.The expression of podocyte specific protein markers including wilms’tumor-1(WT-1)and nephrin were evaluated by immunofluorescence staining and Western blotting analysis.Results The urinary PCR was increased in ADR-induced podocytopathy in mice,with mesangial proliferation,mesangial matrix expansion,podocyte detachment,and the adhesion of glomerular capillary tufts with Bowman’s capsules.The expression levels of podocyte specific protein biomarkers(WT-1 and nephrin)decreased in ADR-induced podocytopathy in mice by immunofluorescence staining and Western blotting.The degree of proteinuria,glomerular injury,and the loss of podocyte specific proteins were attenuated by CDDO-me treatment compared to ADR-induced podocytopathy mice,with similar effect to the traditional therapeutic agent ARB.Conclusion The renal protective role of CDDO-me on kidney damage induced by ADR is related to Nrf2 pathway.