五味子甲素通过抑制NLRP3炎症小体活化减轻失血性休克大鼠的肾脏损伤

Schizandrin A alleviates hemorrhagic shock-induced renal injury via inhibiting activity of NLRP3 inflammasome

目的:探讨五味子甲素对失血性休克大鼠肾脏损伤的作用及作用机制。方法:复制失血性休克大鼠模型并给予不同浓度五味子甲素。试剂盒检测血清血肌酐(Scr)、血尿氮(BUN)含量及线粒体中琥珀酸脱氢酶(SDH)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性。qRT-PCR检测炎症因子的mRNA水平,Western blot检测NLRP3炎症小体活化的标记因子的表达。结果:五味子甲素(40 mg/kg,80 mg/kg)能显著降低血清BUN和Scr的含量;同时,五味子甲素(80mg/kg)能明显升高线粒体中SDH、SOD和GSH-Px的活性,降低IL-1β和TNF-α的mRNA和蛋白表达水平;此外,五味子甲素还可明显抑制NLRP3炎症小体活化的标记因子Caspase-1的表达。结论:五味子甲素可通过抑制NLRP3炎症小体活化减轻失血性休克大鼠肾损伤。

Objective:To investigate the effects and mechanism of schizandrin A(Sch A)on hemorrhagic shock induced-renal injury.Methods:Using a decompensated hemorrhagic shock model and treated rats with Sch A.The blood samples were assayed for blood urea nitrogen(BUN)and serum creatinene(Scr),and mitochondria were isolated from kidney samples for calculating the activities of succinate dehydrogenase(SDH),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px).The mRNA levels of inflammatory cytokines were measured by qRT-PCR.Western blot was performed for protein level.Results:Sch A(40mg/kg,80mg/kg)significantly restored the renal function as demonstrated by increased BUN and Scr.Meanwhile,treatment with Sch A(80mg/kg)increased activities of SDH,SOD and GSH-Px markedly.In addition,Sch A decreased the mRNA and protein levels of IL-1βand TNF-α.Furthermore,Sch A inhibited expression of Caspase-1notablely.Conclusion:Sch A attenuates hemorrhagic shock induced-renal injury by inhibiting the activation of NLRP3inflammasome.