目的 探讨山楂原花青素(HPC)和维生素C(VC)联合应用对胰岛素抵抗(IR)大鼠肝脏氧化应激的影响。方法 高脂饮食法制备IR大鼠模型,检测大鼠造模后体质量、空腹血糖、血清胰岛素水平,试剂盒法检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)和碱性磷酸酶(ALP)活性;将IR大鼠分为模型组、HPC(56 g/kg)组、VC(180 g/kg)组、HPC(56 g/kg)+VC(180 g/kg)组和罗格列酮(122 g/kg)组,连续给药12周,测定各组大鼠肝匀浆中葡萄糖、胰岛素、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-Px)、还原型谷胱甘肽(GSH)、丙二醛(MDA)水平和肝线粒体中SOD、GSH-Px、Na⁺, K⁺-ATP酶、Ca²⁺, Mg²⁺-ATP酶及MDA水平;实时荧光定量PCR(RT-PCR)检测过氧化物酶体增殖物激活受体γ(PPAR-γ)mRNA表达;Western blotting法检测PPAR-γ蛋白表达情况。结果 与对照组比较,造模后大鼠体质量显著下降(P<0.05),血糖、血清胰岛素水平、ALT、AST和ALP活性均显著升高(P<0.01);模型组大鼠肝匀浆中SOD、CAT、GSH-Px、GSH活性均显著下降(P<0.01),葡萄糖、胰岛素、MDA水平显著升高(P<0.01),肝线粒体中SOD、GSH-Px、Na⁺, K⁺-ATP酶、Ca²⁺, Mg²⁺-ATP酶活性均显著降低(P<0.01),MDA水平显著升高(P<0.01);肝组织PPAR-γ mRNA、蛋白表达明显下降(P<0.01)。HPC、VC、HPC+VC和罗格列酮对上述指标均有改善作用,HPC+VC组作用优于HPC组和VC组,与罗格列酮组效果相当。结论 HPC和VC联合作用可改善IR大鼠肝脏氧化应激状态。

Objective To explore the effect of hawthorn proanthocyanidins (HPC) and vitimin C (VC) on liver oxidative stress in insulin-resistance rats. Methods The insulin-resistance models were prepared by high-fat diet, the weight variations of all rats were tested before and after modeling, so were the contents of fasting blood-glucose and serum insulin after modeling. The colorimetric technique was used to test the concentration of serum ALT, AST, and ALP. The rats in high-fat diet group, who were succeeded in modeling, were divided into model, HPC (56 g/kg), VC (180 g/kg), HPC (56 g/kg)+VC (180 g/kg), and rosiglitazone (122 g/kg) groups. After 12 weeks of continuous administration, these indexes, such as levels of SOD, CAT, GSH-Px, GSH, and MDA in liver homogenates and SOD, GSH-Px, Na⁺, K⁺-ATPase, Ca²⁺, Mg²⁺-ATPase, and MDA in liver mitochondria, were all tested; RT-PCR was used to test the expression of PPAR-γ mRNA; The Western blotting method was adopted to test the PPAR-γ protein expression. Results After modeling, the body weight of rats decreased significantly (P<0.05), the concentration of blood, such as glucose, serum insulin ALT, AST, and ALP all increased significantly (P<0.01); The model group was compared with control group, the activities of SOD, CAT, GSH-Px, and GSH were significantly decreased (P<0.01), the levels of glucose, insulin, and MDA increased significantly (P<0.01) in rat liver homogenate, the activities of SOD, GSH-Px, Na⁺, K⁺-ATPase, and Ca²⁺, Mg²⁺-ATPase were significantly decreased (P<0.01) and MDA level increased significantly (P<0.01) in the liver mitochondria; PPAR-γ mRNA and protein expression decreased significantly in liver tissue (P<0.01). HPC, VC, HPC+VC, and rosiglitazone improved the above indexes, which in the HPC+VC group was better than that in the HPC group and VC group, equivalent to that in rosiglitazone group. Conclusion Liver oxidative stress which is resulted from insulin-resistance can be improved when HPC and VC are combined.

国家自然科学基金资助项目(81302423);滨州医学院科技计划项目(BY2013KJ86)