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糖肝煎剂通过激活 IRS/PI3K/AKT 信号通路改善大鼠 2 型糖尿病伴非酒精性脂肪性肝病。

Tangganjian decoction ameliorates type 2 diabetes mellitus and nonalcoholic fatty liver disease in rats by activating the IRS/PI3K/AKT signaling pathway.

机构信息

Science and Education Department, Wuhan Hospital of Traditional Chinese Medicine, Wuhan, Hubei 430014, PR China; Post-doctoral Research Center of Mayinglong Pharmaceutical Group Co., Ltd., Wuhan, Hubei 430060, PR China.

Department of pharmacy, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, Hubei 441099, PR China.

出版信息

Biomed Pharmacother. 2018 Oct;106:733-737. doi: 10.1016/j.biopha.2018.06.089. Epub 2018 Jul 11.

Abstract

AIM

Previous clinical studies have demonstrated that tangganjian (TGJ), a modern Chinese prescribed medicine, has a clinical effect in the treatment of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD). Our study aimed to investigate whether the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is involved in this therapeutic effect.

MATERIALS AND METHODS

T2DM and NAFLD rat models were constructed and treated with three different concentrations of TGJ. Pioglitazone was used as a positive control, along with the model and normal groups. For analyses, blood and livers were collected. Levels of glucose and lipid metabolism indicators, including fasting insulin and total cholesterol, were determined. The expression levels of insulin receptor substrate (IRS), PI3K, and AKT were also determined by western blotting and immunohistochemistry. Liver tissues were stained with hematoxylin & eosin.

RESULTS

In the high-dose TGJ-treated and positive groups, there was a significant increase in the HDL-C level and decreases in the levels of the fasting blood glucose, 2 h postprandial blood glucose, fasting insulin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol, along with a significant increase in the expression of IRS, PI3K, and AKT in the liver. TGJ could also attenuate or counteract the effects of T2DM and NAFLD in the liver lobules.

CONCLUSION

A high concentration of TGJ can improve glucose and lipid metabolism by activating the IRS/PI3K/AKT signaling pathway.

摘要

目的

先前的临床研究表明,现代中药糖肝煎(TGJ)在治疗 2 型糖尿病伴非酒精性脂肪性肝病(NAFLD)方面具有临床疗效。本研究旨在探讨磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(AKT)信号通路是否参与这种治疗作用。

材料和方法

构建 2 型糖尿病伴 NAFLD 大鼠模型,并给予三种不同浓度的 TGJ 进行治疗。吡格列酮作为阳性对照,同时设立模型组和正常组。收集血液和肝脏进行分析。测定血糖和血脂代谢指标,包括空腹胰岛素和总胆固醇的水平。通过 Western blot 和免疫组化测定胰岛素受体底物(IRS)、PI3K 和 AKT 的表达水平。对肝组织进行苏木精和伊红染色。

结果

在高剂量 TGJ 治疗组和阳性对照组中,HDL-C 水平显著升高,空腹血糖、餐后 2 小时血糖、空腹胰岛素、甘油三酯、总胆固醇和低密度脂蛋白胆固醇水平显著降低,IRS、PI3K 和 AKT 在肝脏中的表达显著增加。TGJ 还可以减轻或对抗肝小叶中 2 型糖尿病和非酒精性脂肪性肝病的作用。

结论

高浓度的 TGJ 通过激活 IRS/PI3K/AKT 信号通路改善葡萄糖和脂代谢。

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