垂盆草总黄酮对肝损伤大鼠肝细胞活性的作用机制

The mechanism of action of total flavonoids from Sedum sarmentosum Bunge on Hepatocyte Activity in Rats with Liver Injury

目的探究垂盆草总黄酮对肝损伤大鼠肝细胞活性的作用机制。方法将60只8周龄雄性SD大鼠随机分为正常组(NC组)、肝损伤大鼠模型组(LI组)、联苯双酯组(BDS组)、垂盆草总黄酮1组(SSTF1组)、垂盆草总黄酮2组(SSTF2组)、垂盆草总黄酮3组(SSTF3组),每组各10只。检测各组大鼠肝指数、生化指标谷草转氨酶(Aspartate aminotransferase,AST)和谷丙转氨酶(Alanine aminotransferase,ALT)、氧化指标微量还原型谷胱甘肽(Glutathione,GSH)、超氧化物歧化酶(Superoxidedismutase,SOD)、丙二醛(Malondialdehyde,MDA);检测肝组织病理学变化、肝细胞凋亡指数、自噬相关蛋白IC3、Beclin-1表达、JAK2和STAT3 mRNA表达。结果与NC组比较,LI组大鼠肝指数、ALT、AST、SOD、GSH水平及AI均明显升高,MDA水平明显降低,差异有统计学意义(P<0.05);SSTF1组、SSTF2组和SSTF3组肝指数、ALT、AST、SOD、GSH水平及AI均低于LI组,MDA水平明显高于LI组,差异均有统计学意义(P<0.05)。与NC组比较,LI组大鼠肝组织中IC3-Ⅱ/IC3-Ι比值、Beclin-1蛋白表达及JAK2、STAT mRNA表达明显增加,差异有统计学意义(P<0.05);SSTF1组、SSTF2组、SSTF3组大鼠肝组织中IC3-Ⅱ/IC3-Ι比值、Beclin-1蛋白表达及JAK2、STAT mRNA表达明显低于LI组,差异均有统计学意义(P<0.05)。结论垂盆草总黄酮可减少肝损伤大鼠肝细胞凋亡,降低自噬相关蛋白IC3蛋白表达,抑制JAK/STAT信号通路,进而防治肝损伤。

Objective To explore the mechanism of total flavonoids from Sedum sarmentosum Bunge(SSTF)in regulatinghepatocyte activity in the rats with liver injury.Methods Sixty 8-week-old male SD rats were randomly assigned into anormal control(NC)group,a liver injury(LI)model group,a BDS group,a SSTF1 group,a SSTF2 group,and a SSTF3 group,with 10 rats in each group.The liver index,biochemical indicators[aspartate aminotransferase(AST)and alanine aminotransferase(ALT)],and oxidation indicators[traces of reduced glutathione(GSH),superoxide dismutase(SOD),and malondialdehyde(MDA)]were measured.Furthermore,the liver histopathological changes,hepatocyte apoptosis index,protein levels of autophagy-associated proteins[microtubule-associated proteins light chain 3(IC3)and Beclin-1],and the mRNA levels of Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)were observed and determined.Results The LI group showed higher liver index,higher levels of ALT,AST,SOD,and GSH,higher AI,and lower MDA level than the NC group(P<0.05).The SSTF1,SSTF2,SSTF3 groups had lower liver index,lower levels of ALT,AST,SOD,and GSH,lower AI,and higher MDA level than the LI group(P<0.05).Compared with those in the NC group,the ratio of IC3-II/IC3-I,the protein level of Beclin-1,and the mRNA levels of JAK2 and STAT3 in the liver tissue were up-regulated in the LI group(P<0.05).The ratio of IC3-II/IC3-I,the protein levelof Beclin-1,and the mRNA levels of JAK2 and STAT3 in liver tissue of SSTF1,SSTF2,and SSTF3 groups were lower than those of the LI group(P<0.05).Conclusion SSTF can reduce the apoptosis of hepatocytes,down-regulate the expression of autophagy-associated protein IC3,and inhibit the JAK/STAT signaling pathway,thus preventing and treating liver injury in rats.