虎杖苷对ApoE^(-/-)小鼠肝脏miR-214表达水平及肝功能的影响

Effect of polydatin on miR-214 expression and liver function in ApoE^(-/-) mice

目的研究虎杖苷(PD)对Apo E-/-小鼠肝脏mi R-214及肝功能的影响。方法采用高脂饲料喂养雄性Apo E-/-小鼠,建立小鼠AS模型。将Apo E-/-小鼠随机分为4组(n=10),即模型组(Model)、辛伐他汀组(Simvastatin)、PD低剂量组(PDL)、PD高剂量组(PDH),另设10只同龄C57BL/6J小鼠为正常对照组。连续给药12周后取血,检测小鼠血糖、血脂、谷草转氨酶(AST)、谷丙转氨酶(ALT)、肝脏T-SOD及MDA等指标,HE染色观察肝组织病理切片,实时荧光定量PCR检测mi R-214水平。结果模型组小鼠血糖和血清中TC、TG、LDL-C、ALT和AST,以及肝脏中MDA较正常对照组显著增高(P<0.01),血清中HDL-C和肝脏中TSOD、mi R-214则显著降低(P<0.01),肝切片可见细胞内充满大小不一脂滴,大部分肝细胞呈现脂肪变性;与模型组相比,PD高剂量组能显著降低小鼠空腹血糖、血清TC、TG、LDL-C、AST、ALT以及肝脏中的MDA(P<0.05),并且能够显著升高血清HDLC和肝脏mi R-214及T-SOD(P<0.05);PD高、低剂量组小鼠肝细胞脂肪变性与模型组相比均有所减轻。结论 PD能降低AS小鼠血糖、血脂,并保护肝功能,其机制可能主要与PD升高肝脏mi R-214水平,调节T-SOD与MDA等氧化应激指标有关。

Objective To study the effect of polydatin on the expression level of mi R- 214 and liver function in atherosclerotic mice. Methods Forty male Apo E^-/-mice were randomly allocated into 4 groups（n=10）, namely the model group, low- and highdose polydatin groups, and simvastin group, with 10 male C57BL/6J mice serving as the normal control group. Mouse models of atherosclerosis were established by feeding the Apo E^-/-mice with a high-fat diet. After 12 weeks of treatment, blood levels of glucose, lipids, AST, and ALT and the contents of T- SOD and MDA in the liver tissue were detected. The pathologies of the liver were examined with HE staining, and mi R- 214 expression in the liver was detected using quantitative real- time PCR.Results Compared with the normal control mice, the mice in the model group showed significantly increased blood glucose,serum TC, TG, LDL-C, ALT, and AST levels, and MDA contents in the liver（P〈0.01）, with significantly decreased serum HDLC level and SOD and mi R- 214 levels in liver（P〈0.01）. Polydatin treatment significantly ameliorated such changes in blood glucose, serum ALT, AST, TC, TG, LDL- C, and HDL- C levels, and MDA, SOD, and mi R- 214 contents in liver tissue（P〈0.05）.Conclusions Polydatin can reduce blood glucose and lipid levels and protect the liver function in atherosclerotic mice possibly by up-regulating the expression of mi R-214 and T-SOD and down-regulating MDA in the liver.