葛根芩连汤不同部位及其组合对胰岛素抵抗大鼠ADIPOR/AMPK信号通路的影响

Effects of Different Parts of Gegen Qinlian Decoction and Their Combinations on ADIPOR/AMPK Signaling Pathway in Insulin Resistance Rats

关键词:  葛根芩连汤  活性部位  胰岛素抵抗  脂联素受体  AMP依赖的蛋白激酶

Key words:  Gegen Qinlian Decoction  active site  insulin resistance  adiponectin receptor  AMP-dependent protein kinase

摘要:

目的 考察葛根芩连汤不同部位单用及联用对胰岛素抵抗大鼠的药理活性及对ADIPOR/AMPK通路的影响，阐明葛根芩连汤防治胰岛素抵抗的药效物质基础。方法 葛根芩连汤分为总黄酮、总皂苷、总生物碱和总多糖部位，考察各个不同部位单用对胰岛素抵抗大鼠的体态、血脂四项、胰岛素抵抗指数和胰岛素敏感指数的影响，综合分析筛选活性部位；再将活性部位组合给药，通过ELISA和Western blotting试验考察不同部位单用及联用对ADIPOR/AMPK信号通路的影响。结果 葛根芩连汤中总黄酮、总生物碱均可显著改善胰岛素抵抗大鼠异常的体态、血脂四项及胰岛素抵抗状态，总皂苷可显著降低胰岛素抵抗大鼠的TC、LDL-C、INS的含量，对其他指标的影响不具有统计学意义，故而将总黄酮、总生物碱、总皂苷组合后给药，考察部位间的交互作用。结果表明，总黄酮、总生物碱单用及联用时，均可显著提升胰岛素抵抗大鼠肝组织中ADIPOR、CaMKK2、AMPKα、p-AMPK的表达，显著抑制SREBP1的表达，且总黄酮与总皂苷、总生物碱与总皂苷联用时作用增强，对ADIPOR、CaMKK2、AMPKα、p-AMPK的影响与三者单用时差异有统计学意义，表明总黄酮与总皂苷、总生物碱与总皂苷之间存在有一定的交互作用。结论 葛根芩连汤防治胰岛素抵抗的机制可能是通过总黄酮、总生物碱与总皂苷协同激活ADIPOR/AMPK信号通路实现的。

Abstract:

OBJECTIVE To investigate the pharmacological activity of different parts and their combinations of Gegen Qinlian Decoction on ADIPOR/AMPK pathway in insulin resistant rats, and to elucidate the pharmacodynamic material basis of Gegen Qinlian Decoction in the prevention and treatment of insulin resistance. METHODS Gegen Qinlian Decoction was divided into total flavonoids, total saponins, total alkaloids and total polysaccharides. The effects of different parts on body posture, four items of blood lipid, insulin resistance index and insulin sensitivity index of insulin resistance rats were investigated. Active sites were comprehensively analyzed and screened. The effects of single and combined use of different parts on ADIPOR/AMPK signal pathway were investigated by ELISA and Western blotting. RESULTS Total flavonoids and total alkaloids in Gegen Qinlian Decoction could significantly improve the abnormal posture, blood lipids and insulin resistance of insulin resistance rats. Total saponins could significantly reduce the content of TC, LDL-C and INS in insulin-resistant rats, and the effect on other indicators was not statistically significant. Therefore, the three parts were combined and administered to investigate the interaction between the parts. The results showed that when the total flavonoids and total alkaloids were used alone or in combination, could significantly increase the expression of ADIPOR, CaMKK2, AMPKα, and p-AMPK in the liver tissue of insulin resistance rats, and could significantly inhibit the expression of SREBP1. Moreover, the combination effect of total flavonoids and total saponins, total alkaloids and total saponins were enhanced, and the effect on ADIPOR, CaMKK2, AMPKα, p-AMPK were significantly different from those when the three were used alone, which indicated that there was an interaction between total flavonoids and total saponins, total alkaloids and total saponins. CONCLUSION The mechanism of Gegen Qinlian Decoction in the prevention and treatment of insulin resistance rats may be achieved through the synergistic activation of ADIPOR/AMPK signaling pathway by total flavonoids and total saponins, total alkaloids and total saponins.