目的探讨黄芩苷对糖尿病大鼠血糖和血脂的影响及其作用机制。方法以高脂饲料(HFD)喂养雄性SD大鼠6周后,尾静脉iv给予链脲佐菌素(STZ)诱导2型糖尿病模型。黄芩苷组大鼠每天ip给予黄芩苷80 mg.kg-1,连续6周。给药0,3和6周时观察血糖、血总胆固醇(TC)、血三酰甘油(TG);给药6周时测定肝TC和丙二醛(MDA)水平;Western印迹法分析肝和骨骼肌磷酸化腺苷酸活化蛋白激酶(AMPK)及其下游靶蛋白乙酰辅酶A羧化酶(ACC)磷酸化水平。MTT法检测黄芩苷1~50μmol.L-1作用HepG2细胞24 h的细胞存活力;Western印迹法观察黄芩苷对AMPK活性的影响。结果黄芩苷80 mg.kg-1可明显降低糖尿病大鼠的血糖和血TC(P〈0.05);黄芩苷可明显降低糖尿病大鼠肝TC和MDA水平(P〈0.05)。糖尿病模型大鼠肝和骨骼肌磷酸化AMPK和磷酸化ACC的水平显著降低(P〈0.01),而黄芩苷能激活AMPK,明显增加糖尿病大鼠肝和骨骼肌AMPK和ACC的磷酸化水平(P〈0.01)。黄芩苷1和5μmol.L-1无细胞毒性,但能显著增加HepG2肝细胞磷酸化AMPK水平(P〈0.01)。结论黄芩苷对糖尿病大鼠具有一定的保护作用,其作用机制可能与激活肝和骨骼肌AMPK有关。
OBJECTIVE To investigate the effect of baicalin on streptozocin(STZ)-induced diabetic rats with hyperlipidemia.METHODS Male SD rats were fed with high-fat diet(HFD) 6 weeks and iv given STZ 45 mg·kg^-1 to induce a type 2 diabetes model.Baicalin was ip given 80 mg·kg^-1 once daily for 6 weeks.Body mass was measured.The serum glucose,total cholesterol(TC) and triglyceride,liver TC and malondialdehyde(MDA) were analyzed.AMP-activated protein kinase(AMPK) activation in the liver and muscle was examined by measuring AMPK phosphorylation and quantitating phosphorylation of AMPK substrate acetyl-CoA carboxylase(ACC).Effects of baicalin on activation of AMPK in HepG2 cells were also examined.RESULTS Baicalin 80 mg·kg^-1 suppressed serum glucose and TC concentrations in diabetic rats.Baicalin reduced hepatic TC and MDA(P0.05) and enhanced phosphorylation of AMPK and ACC(P0.01).In HepG2 cells,baicalin 1 and 5 μmol·L^-1 increased phosphorylation of AMPK(P0.01).CONCLUSIONBaicalin has protective effects on the development of diabetes by targeting the hepatic and muscular AMPK.