中文摘要：

目的观察小檗碱对胰岛素抵抗大鼠氧化／抗氧化状态和内质网应激（endoplasmic eticulum tress，ER tress）的影响，并探讨其改善胰岛素抵抗的分子机制。方法采用高脂高热卡饮食饲养8wk制备胰岛素抵抗大鼠模型，成模后随机分为小檗碱组（BER组）、Alpha-硫辛酸组（ALA组）和模型组（MOD组），各组以相应的药物干预4wk。另设正常组（NOR组），予普通饲料喂养，不予药物干预。比较各组大鼠空腹血糖（FBG）、空腹胰岛素水平（Fins）和胰岛素敏感性（ISI）。血清中丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）活性以观察药物对大鼠氧化和抗氧化的影响。Western lot方法测定肝脏组织中的ER应激标志物c-Jun氨基端激酶（c-jun NH2-terminal kinase，JNK）和Phospho-c-Jun（Ser73）（p-c-Jun）的含量变化。RT—PCR方法测定肝脏组织ER应激标志物葡萄糖调节蛋白GRP78（slucose regulated protein78，GRP78）mRNA表达水平，以观察小檗碱对胰岛素抵抗大鼠ER应激的影响。结果与NOR组比较，MOD组大鼠血清中MDA含量明显升高，SOD、GSH-Px活性明显降低（P均〈0．05）。BER组大鼠SOD、GSH—Px的活性较MOD组明显升高（P〈0．01，P〈0．05），MDA含量较模型组明显下降。比较各组肝组织p-c-Jun／JNK的水平，MOD组较NOR组明显升高（P〈0．01），BER组及ALA组较MOD组均明显下降（P均〈0．01）。比较各组肝组织中GRP78 mRNA水平，MOD组较NOR组明显升高（P〈0．05），BER组及AIA组较MOD组均明显下降。结论小檗碱能提高胰岛素抵抗大鼠的胰岛素敏感性，增加其抗氧化能力，改善其ER应激状态，其作用机制可能与改善ER应激有关。

英文摘要：

Aim To study the effects of berberine on oxidative stress and endoplasmic reticulum stress of insulin resistant rats, and to explore its possible molecular mechanism. Methods Seventy male wistar rats were fed with a high-fat and high-caloric diet to establish insulin resistance model. After 8 weeks＇ feeding, serum fasting blood glucose （ FBG）, fasting insulin （ Fins ） , insulin sensitivity index （ISI） were determined. Forty-two insulin resistant rats were successfully induced and were randomly divided into model, berberine and alpha-lipoic acid（ALA） groups,with 14 animals in each group. Another 12 normal rats were used as control group. After administration with corresponding drugs for 4 weeks,the rats were sacrificed and serum malonaldehyde （ MDA）, superoxide dismutase （ SOD ）, glutathione peroxidase （ GSH-Px ） were determined. The GRP78 mRNA expression in liver was determined by reversetranscription polymerase chain reaction （RT-PCR）. Western blot analysis was employed to detect liver Phospho-c-Jun /JNK protein expression. Results Compared with control group, model group showed higher MDA level while significantly decreased SOD and GSH-Px activity （P 〈 0. 05 ）. In berberine and ALA groups, SOD and GSH-Px were elevated drastical- ly compared to those of model group（P 〈0. 01 or P 〈 0. 05 ）, while MDA level was significantly decreased compared with that of model group. Protein expression of Phospho-c-Jun/JNK in model group was significantly higher than that in control group while its expression in berberine group was significantly decreased than that in model group （ P 〈 0. 01 ）. The GRP78/Bip mRNA was significantly increased in model group （ P 〈 0. 05 ）, while obviously decreased in berberine and ALA groups compared with normal control. Conclusion Berberine could improve insulin resistance, which might be correlated with its anti-oxidative effect and its preventive effect on endoplasmic reticulum stress.