青藤碱对阿奇霉素诱导的急性肝损伤大鼠的保护作用及机制研究

Protective effect of sinomenine on azithromycin-induced acute liver injury in rats

目的:探索青藤碱对阿奇霉素诱导的大鼠急性肝损伤的影响及其分子机制。方法:SD大鼠随机分为3组:对照组、阿奇霉素(AZM)组和阿奇霉素+青藤碱(AZM+SM)组。苏木素伊红(HE)染色观察肝脏组织病变。脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)检测细胞凋亡。免疫组化检测细胞增殖核抗原-67(Ki-67)表达。ELISA检测IL-6、IL-18和IL-1β水平。蛋白印迹检测p38、p-p38、HSP27和p-HSP27表达。结果:青藤碱可减轻阿奇霉素诱导的急性肝损伤大鼠肝脏组织病变。与对照组相比,阿奇霉素组细胞凋亡增加,Ki67表达下降(P<0. 05)。与阿奇霉素组相比,阿奇霉素+青藤碱组细胞凋亡降低,Ki67表达升高(P<0. 05)。阿奇霉素组IL-6、IL-18和IL-1β水平高于对照组(P<0. 05)。阿奇霉素+青藤碱组IL-6、IL-18和IL-1β水平低于阿奇霉素组(P<0. 05)。与对照组相比,阿奇霉素组p-p38/p38和p-HSP27/HSP27比值上升(P<0. 05)。与阿奇霉素组相比,阿奇霉素+青藤碱组p-p38/p38和p-HSP27/HSP27比值下降(P<0. 05)。结论:青藤碱可通过抑制p38通路的活化减轻阿奇霉素诱导的大鼠急性肝损伤。

Objective:To explore the effect of sinomenine on azithromycin-indcuced acute liver injury in rats.Methods:Rats were divided into three groups:control group,azithromycin(AZM)group and azithromycin+sinomenine(AZM+SM)group.Pathological changes of liver tissue were observed by hematoxylin-eosin(HE)staining.Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick labeling(TUNEL).The expression of Ki67was detected by immunohistochemical staining.The levels of IL-6,IL-18and IL-1βwere detected by ELISA.The expression of p38,p-p38,HSP27and p-HSP27were detected by Western blot.Results:The azithromycin-induced pathological changes of liver tissue were alleviated by sinomenine.Compared with control group,the apoptosis in AZM group was increased with decreased expression of Ki67(P<0.05).Compared with AZM group,the apoptosis in AZM+SM group was reduced with enhancive expression of Ki67(P<0.05).The levels of IL-6,IL-18and IL-1βin AZM group were higher than control group(P<0.05).The levels of IL-6,IL-18and IL-1βin AZM+SM group were lower than AZM group(P<0.05).Compared with control group,the rate of p-p38/p38and p-HSP27/HSP27in AZM group were elevated(P<0.05).Compared with AZM group,the rate of p-p38/p38and p-HSP27/HSP27in AZM+SM group were decreased(P<0.05).Conclusion:Sinomenine alleviates the azithromycin-induced acute liver injury in rats via inhibiting activation of p38pathway.