积雪草苷对代谢相关脂肪性肝病大鼠Nrf2、ROS通路表达的影响

Effects of asiaticoside on Nrf2 and ROS pathway expression in rats with metabolically associated fatty liver disease

目的探究积雪草苷对代谢相关脂肪性肝病大鼠核因子E2相关因子2(Nrf2)、活性氧(ROS)通路表达的影响。方法将大鼠随机分为对照组、模型组、积雪草苷(5、15、30mg/kg)组、双环醇组,每组10只。除对照组外其余均建立脂肪肝模型,对照组与模型组给予ig10mL/kg生理盐水,积雪草苷(5、15、30mg/kg)组分别ig5、15、30mg/kg积雪草苷,双环醇组ig20mg/kg双环醇,1次/d,连续4周。采用ELISA检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平及总胆固醇(TC)、三酰甘油(TG)含量,荧光探针–二氢乙啶(DHE)法检测ROS水平,苏木精–伊红(HE)染色观察病理组织,免疫印迹和PCR分别检测Nrf1、Nrf2蛋白及mRNA相对表达量。结果与模型组比较,积雪草苷15、30mg/kg组ALT、AST、TC、TG、ROS水平显著降低,Nrf1、Nrf2 mRNA及蛋白表达显著升高(P<0.05),对照组大鼠肝脏组织结构完好;积雪草苷15、30mg/kg组及双环醇组大鼠肝细胞脂肪变性有所减轻,汇管区见少量炎细胞浸润。结论积雪草苷可降低代谢相关脂肪性肝病大鼠血清ALT、AST、TC、TG水平,并抑制ROS增长,其机制可能与激活Nrf1、Nrf2相关。

Objective To investigate the effects of asiaticoside on Nrf2 and ROS pathway expression in rats with metabolically associated fatty liver disease.Methods Rats were randomly divided into control group,model group,asiaticoside(5,15,30 mg/kg)group,and bicyclic alcohol group,with 10 rats in each group.Control group and model group were ig 10 mL/kg normal saline,asiaticoside(5,15,30 mg/kg)group were ig 5,15,30 mg/kg asiaticoside,bicyclic alcohol group were ig 20 mg/kg bicyclic alcohol group,once daily for 4 weeks.ELISA was used to detect ALT,AST,TC,and TG,fluorescent probe dihydroethidine(DHE)method was used to detect ROS,and HE staining was used to observe the pathological tissue.The relative expression levels of Nrf1 and Nrf2 protein and mRNA were detected by Western blotting and PCR respectively.Results Compared with model group,ALT,AST,TC,TG and ROS in 15 and 30 mg/kg asiaticoside groups were significantly decreased,while Nrf1 and Nrf2 mRNA and protein were significantly increased(P<0.05).The liver structure of control group was intact.The hepatocyte steatosis of 15,30 mg/kg asiaticoside group and dicyclol group was reduced,and a small amount of inflammatory cell infiltration was observed in the sink area.Conclusion Asiaticoside can reduce the levels of ALT,AST,TC,and TG in serum of rats with metabolism-related fatty liver disease,and inhibit the growth of ROS,which may be related to the activation of Nrf1 and Nrf2.