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中药黄芪改善低剂量地塞米松处理大鼠胰岛素敏感性的分子基础

颜廷艳, 武晓光, 张英涛*   

  1. 北京大学药学院 天然药物学系, 北京 100083
  • 收稿日期:2007-03-15 修回日期:2007-08-10 出版日期:2007-09-15 发布日期:2007-09-15
  • 通讯作者: 张英涛*

Molecular mechanism of Radix astragali on improvement of insulin sensitivity of SD rats treated with low dose dexamethasone

Ting-Yan Yan, Xiao-Guang Wu, Ying-Tao Zhang*   

  1. School of Pharmaceutical Sciences, Peking University, Beijing 100083, China
  • Received:2007-03-15 Revised:2007-08-10 Online:2007-09-15 Published:2007-09-15
  • Contact: Ying-Tao Zhang*

摘要: 目的 研究中药黄芪的多糖部分与皂苷部分对地塞米松诱导胰岛素抵抗大鼠的胰岛素敏感性的影响, 探讨何者为黄芪改善作用的主要活性部位及其对胰岛素抵抗相关基因表达的影响。方法 2 μg/天的剂量给雄性SD大鼠(每组6)皮下注射地塞米松注射液, 连续4, 同时给以相同生药剂量(10 g生药/kg)的黄芪多糖提取物或黄芪皂苷提取物。试验结束后, 动物处死取血, 测定血清甘油三酯、总胆固醇、高密度脂蛋白、低密度脂蛋白、血糖与胰岛素水平; 取肾脏组织与睾丸脂肪垫提取总RNA, 采用RT-PCR方法分别检测血管紧张素原(angiortensinogen)、脂联素(adiponectin)、瘦素(leptin)、肿瘤坏死因子(TNF-α)与甘油醛-3-磷酸脱氢酶(GAPDH)基因的表达水平。结果 黄芪多糖提取物与黄芪皂苷提取物均表现出降低大鼠血清甘油三酯、血糖与胰岛素水平的作用, 在同等生药剂量下, 黄芪皂苷组对大鼠胰岛素敏感性指数的改善优于黄芪多糖组。两种提取物均能显著降低肾脏组织中血管紧张素原的表达及脂肪组织中肿瘤坏死因子α的表达, 并同时上调脂联素与瘦素基因的表达, 两种处理间未发现显著性差异。结论 中药黄芪的多糖部分与皂苷部分均有增加胰岛素敏感性的作用, 该作用可能与下调血管紧张素原、肿瘤坏死因α基因及上调脂联素与瘦素基因的RNA水平密切相关, 部分说明了黄芪对II型糖尿病与糖尿病肾病的改善作用。两个提取部分未表现出作用上的显著性差异提示其中可能含有其他共性的重要活性成分有待发现。

关键词: 黄芪, 黄芪, 黄芪, 胰岛素抵抗, 胰岛素抵抗, 胰岛素抵抗, 血管紧张素原, 血管紧张素原, 血管紧张素原, 脂联素, 脂联素, 脂联素, 瘦素, 瘦素, 瘦素, 肿瘤坏死因子α, 肿瘤坏死因子α, 肿瘤坏死因子α

Abstract:

Aim To reveal the main active components and the action mechanisms of Radix astragali on insulin sensitivity improvement, we have investigated the effects of polysaccharide portion and saponin portion of Radix astragali extracts on blood biochemical indices and related gene expression of dexamethasone-induced SD rats. Methods SD rats (6 per group) received 2 μg/day subcutaneous dexamethasone for 4 weeks plus same dose (10 g material/kg) of polysaccharide or saponin extracts of Radix astragali. Blood samples, kidney tissues and epididymal fat pads were taken at the end of the experiment. Serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), glucose (GLU) and insulin (INS) levels were measured, respectively. mRNA levels of angiotensinogen in kidney, adiponectin and leptin as well as TNF-α in epididymal fats were determined by RT-PCR assay using GAPDH gene as an internal control. Results Both of polysaccharide and saponin extracts of Radix astragali exhibited positive effects in reducing serum triglycerides, glucose, and insulin levels of dexamethasone-induced SD rats. The saponin group showed more improvements on quantitive insulin sensitivity check index (QUICKI) than the polysaccharide group did. Both of the extracts down-regulated kidney angiotensinogen and fat TNF-α mRNA levels while they were simultaneously up-regulating fat adiponectin and leptin mRNA levels. No significant difference was found between actions of the two extracts. Conclusion Both of polysaccharide and saponin extracts of Radix astragali can improve insulin sensitivity. This action might be closely related to down-regulation of angiotensinogen, TNF-α and up-regulation of adiponectin and leptin expression. The results partly explained the improvement of type II diabetes and diabetic nephropathy by Radix astragali. The similar actions of the two crude extracts suggest that unknown key active compounds might exist in both and remain to be discovered.

Key words: Radix astragali, Radix astragali, Insulin resistance, Insulin resistance, Angiotensinogen, Angiotensinogen, Adiponectin, Adiponectin, Leptin, Leptin, TNF-α, TNF-α

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Supporting: *Corresponding author. Tel.: 86-10-82801559