山茱萸环烯醚萜总苷对小鼠胰岛素抵抗和非酒精性肝损伤的改善作用及其机制研究

Study on effect and mechanism of iridoid glycoside from cornus officinalis on mice with nonalcoholic liver injury and insulin resistance

关键词:  山茱萸环烯醚萜总苷  肝损伤  胰岛素抵抗  作用机制

Key words:  iridoid glycoside from cornus officinalis  liver injury  insulin resistance  effect mechanism

摘要:

[目的]探讨山茱萸环烯醚萜总苷（ICO）对胰岛素抵抗和非酒精性肝损伤的改善作用及其作用机制。[方法]采用摄入高脂饲料的方法构建肥胖糖尿病大鼠模型，设置正常组、模型组、吡格列酮对照组和ICO低、中、高剂量组共5个实验组，给药3周，酶联免疫吸附（ELISA）方法测定血清中谷丙转氨酶（ALT）、谷草转氨酶（AST）、血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、胰岛素和肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、白细胞介素1β（IL-1β）水平，蛋白免疫印迹（Western Blot）法测定肝脏组织p-P65，p-ERK1/2，p-JNK1/2，p-P38蛋白表达水平。[结果]ICO可以显著降低肥胖小鼠脂肪指数、降低血清中ALT、AST、TC、TG、LDL、HDL、胰岛素、TNF-α、IL-6、IL-1β水平，改善葡萄糖耐量和胰岛素耐量，降低肝脏组织p-P65，p-ERK1/2，p-JNK1/2，p-P38蛋白表达水平。[结论]ICO可改善小鼠胰岛素敏感水平和肝损伤程度，这可能与其能够降低P65，ERK1/2，JNK1/2，P38蛋白磷酸化水平，抑制核因子-κB （NF-κB）和MAPKs信号通路激活，从而降低机体炎性水平有关。

Abstract:

[Objective] To investigate the effect and mechanism of iridoid glycoside from cornus officinalis (ICO) on insulin resistance and nonalcoholic liver injury in mice.[Methods] Mice were divided into normal group, model group, Pioglitazone group, ICO low, middle and high dose group, administrating for 3 weeks respectively. Mice were fed with high-fat diet (HFD) to induce obesity and diabetes. The level of ALT, AST, TC, TG, LDL, HDL, insulin, TNF-α,IL-6 and IL-1β were measured by ELISA method, expression level of p-P65,p-ERK1/2,p-JNK1/2 and p-P38 were detected by Western Blot method.[Results] Administration of ICO can significantly reduced the fat index, the level of serum ALT, AST, TC, TG, LDL, HDL, insulin, TNF-α, IL-6 and IL-1β, the expression level of p-P65,p-ERK1/2,p-JNK1/2 and p-P38 and improved glucose and insulin tolerance of the obese mice.[Conclusion] ICO can improve insulin resistance and nonalcoholic liver injury in mice significantly. The effect may be acted through reduce the expression level of p-P65,p-ERK1/2,p-JNK1/2 and p-P38, then inhibit NF-κB and MAPK pathway activation and inflammatory reaction.