非诺贝特对梗阻性黄疸大鼠肝细胞凋亡、肝糖原含量的影响

Effect of fenofibrate on hepatocyte apoptosis and hepatic glycogen in rats with obstructive jaundice

目的探讨非诺贝特对胆管结扎大鼠血清肝脏生化指标、肝细胞凋亡、肝糖原含量的影响。方法采用胆总管结扎手术制备胆汁淤积大鼠模型。48只雄性W istar大鼠随机分为4组(每组均为12只):A组为对照组,B组为胆管结扎组,C组为胆管结扎+非诺贝特组(30 mg.kg-1.d-1),D组为胆管结扎+非诺贝特(60 mg.kg-1.d-1)。术后7 d留取血标本及肝组织后处死,分别用全自动生化分析仪测定血清ALT、AST、ALP、GGT、TBA,TUNEL法检测肝细胞凋亡数目以及过碘酸希夫(PAS)染色法检测肝糖原含量。结果 B、C、D组大鼠血清ALT、AST、ALP、GGT、TBA显著高于A组(P<0.001),B组与C组大鼠血清ALT、AST、ALP、GGT、TBA差异无统计学意义,D组血清AST、ALP、GGT、TBA显著低于B、C组(P<0.01),而ALT在D与C组之间差异无统计学意义(P=0.021>0.01)。所有胆管结扎组大鼠肝细胞凋亡显著高于对照组(P<0.001),C组肝细胞凋亡显著低于B组(P=0.007<0.01),D组肝细胞凋亡显著低于B组(P=0.000<0.001),D组肝细胞凋亡显著低于C组(P=0.000<0.001)。PAS反应显示,非诺贝特可增加梗阻性黄疸大鼠肝糖原合成。结论非诺贝特可显著改善梗阻性黄疸大鼠血清肝脏生化指标、肝细胞凋亡以及增加肝细胞糖原合成。

Objective To investigate the effect of Fenofibrate on serum biochemical indicators,apoptosis and hepatic glycogen in rats with obstructive jaundice.Methods Rats were subjected to bile duct ligation to establish the cholestasis model.Forty-eight male Wistar rats were randomly divided into four groups equally： Group A = control group,Group B = bile duct ligation（BDL）,Group C = BDL ＋ Fenofibrate（30 mg/kg daily）.Group D = BDL ＋ Fenofibrate（60 mg/kg daily）.All rats were sacrificed on 7th day after obtaining blood samples and liver tissue.Serum ALT,AST,ALP,GGT,TBA were tested by automatic chemistry analyzer,the number of hepatocyte apoptosis were tested by TUNEL and hepatic glycogen were tested by PAS.Results Serum ALT,AST,ALP,GGT,TBA levels in rats with BDL were significantly higher than in the group A（P0.001）.There was no significant difference in terms of serum ALT,AST,ALP,GGT,TBA levels between group B and group C.Serum ALT,AST,ALP,GGT,TBA levels in rats of group D were significantly lower than in group B,C（P0.01） except ALT between Group D and Group C（P=0.0210.01）.Hepatocyte apoptosis in rats with BDL were significantly higher than in the control group（P0.001）.Hepatocyte apoptosis in the animals of group C were significantly lower than in group B（P=0.0070.01） when hepatocyte apoptosis in group D were significantly lower than in group B or C（P=0.0000.001）.Periodic acid schiff（PAS） reaction indicated that fenofibrate can strengthen hepatic glycogen synthesis in rats with obstructive jaundice.Conclusion Fenofibrate administration attenuates serum biochemical indicators、hepatocyte apoptosis and strengthen hepatic glycogen synthesis in rats with obstructive jaundice.