异槲皮苷调控线粒体动力学逆转造影剂所致大鼠急性肾损伤

Effects of isoquercitrin on mitochondrial dynamics and reversal of contrast media induced acute kidney injury in rats

探究异槲皮苷对造影剂所致大鼠急性肾损伤的治疗作用及机制,通过建立碘普罗胺370注射液诱发的大鼠造影剂所致肾病模型,采用每天25、50 mg/kg异槲皮苷和阳性药N-乙酰半胱氨酸(NAC)进行预处理治疗,检测大鼠肾脏血肌酐水平、组织形态学、丙二醛(MDA)和H_(2)O_(2)水平、还原性谷胱甘肽(GSH)和8-羟基脱氧鸟苷(8-OHDG)水平;采用原位末端缺刻标记法(TUNEL)、半胱天冬酶3(caspase-3)活性检测肾脏组织的凋亡情况;免疫组织化学检测多腺苷二磷酸多聚酶(Cleaved PARP)、线粒体融合蛋白2(MFN2)和线粒体动力相关蛋白1(DRP1)的表达和免疫印迹法检测肾脏组织MFN2和DRP1的表达。结果表明:异槲皮苷可以有效减轻造影剂碘普罗胺所致的急性肾损伤,缓解肾脏组织的氧化应激状态,改善线粒体动力学失衡。本研究结果将为异槲皮苷进一步被开发成为造影剂所致肾病急性肾损伤的治疗药物提供理论基础。

To explore the therapeutic effect and mechanism of isoquercetin on contrast induced acute kidney injury in rats,the contrast induced nephropathy model of rats induced by ioprolamine 370 injection was established and treated with 25 and 50 mg/kg isoquercetin and positive drug N-acetylcysteine(NAC) every day.Serum creatinine levels,histomorphology,malondialdehyde(MDA) and hydrogen peroxide(H_2O_2) levels,glutathione(GSH) and 8-hydroxy-deoxyguanosine(8-OHDG) levels were detected.The apoptosis of renal tissue was detected by TUNEL and caspase-3 activity.Immunohistochemistry was used to detect the expression of Cleaved PARP,mitochondrial fusion protein 2(MFN2),and mitochondrial power-associated protein 1(DRP1),and Western blotting was used to detect the expression of MFN2 and DRP1 in renal tissues.Studies have shown that isoquercitrin can effectively relieve acute kidney injury induced by ioprolamine,relieve the oxidative stress state of renal tissue,and improve the imbalance of mitochondrial dynamics.The results of this study will provide a theoretical basis for the further development of isoquercitrin as a drug for the treatment of contrast-induced nephropathy with acute kidney injury.