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三黄泻心汤通过调节代谢谱和NF-κB/PI-3K/Akt信号通路改善2型糖尿病大鼠。

Sanhuang Xiexin Tang Ameliorates Type 2 Diabetic Rats via Modulation of the Metabolic Profiles and NF-κB/PI-3K/Akt Signaling Pathways.

作者信息

Wei Xiaoyan, Tao Jinhua, Shen Yumeng, Xiao Suwei, Jiang Shu, Shang Erxin, Zhu Zhenhua, Qian Dawei, Duan Jinao

机构信息

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing, China.

School of Pharmacy, Nantong University, Nantong, China.

出版信息

Front Pharmacol. 2018 Aug 28;9:955. doi: 10.3389/fphar.2018.00955. eCollection 2018.

Abstract

Sanhuang Xiexin Tang (SXT), a classic prescription, has been clinically used to cure diabetes for thousands of years, but its mechanism remains unclear. Here, a systematic in-depth research was performed to unravel how it worked by the signaling pathway and metabonomics analysis. Our studies were conducted using high-fat diets (HFD) and streptozocin (STZ)-induced type 2 diabetes mellitus (T2DM) rats. The blood glucose was measured by a glucose-meter. Protein contents were determined by western blotting or ELISA and mRNA expression was identified by RT-PCR analysis. The pathological status of pancreas was assessed by histopathological analysis. Furthermore, Ultra Performance Liquid Chromatography-Quadrupole-Time of Flight/Mass Spectrometry (UPLC-Q-TOF/MS) coupled with multivariate statistical analysis was performed to discover potential biomarkers and the associated pathways. Hyperglycaemia, insulin resistance, dyslipidemia and inflammation in T2DM rats were significantly ameliorated after 7-week oral administration of SXT. The expressions of phosphatidylinositol-3-kinase (PI-3K), protein kinase B (Akt), glucose transporters-4 (GLUT4) Mrna, and p-PI-3K, p-Akt, GLUT4 protein involved in the PI-3K/Akt signaling pathway of T2DM were markedly up-regulated. Further investigation indicated that the perturbance of metabolic profiling in T2DM rats was obviously reversed by SXT and 38 potential biomarkers were screened and identified. Our study might help clarify the mechanism of SXT and provide some evidences for its clinical application in the future.

摘要

三黄泻心汤(SXT)是一个经典方剂,数千年来一直被临床用于治疗糖尿病,但其作用机制尚不清楚。在此,通过信号通路和代谢组学分析进行了系统深入的研究,以阐明其作用方式。我们的研究使用高脂饮食(HFD)和链脲佐菌素(STZ)诱导的2型糖尿病(T2DM)大鼠进行。用血糖仪测量血糖。通过蛋白质印迹法或酶联免疫吸附测定(ELISA)测定蛋白质含量,通过逆转录-聚合酶链反应(RT-PCR)分析鉴定mRNA表达。通过组织病理学分析评估胰腺的病理状态。此外,采用超高效液相色谱-四极杆-飞行时间/质谱联用仪(UPLC-Q-TOF/MS)结合多变量统计分析来发现潜在生物标志物及相关通路。对T2DM大鼠口服SXT 7周后,其高血糖、胰岛素抵抗、血脂异常和炎症得到显著改善。参与T2DM大鼠PI-3K/Akt信号通路的磷脂酰肌醇-3-激酶(PI-3K)、蛋白激酶B(Akt)、葡萄糖转运蛋白4(GLUT4)mRNA以及p-PI-3K、p-Akt、GLUT4蛋白的表达均明显上调。进一步研究表明,SXT明显逆转了T2DM大鼠代谢谱的紊乱,并筛选鉴定出38种潜在生物标志物。我们的研究可能有助于阐明SXT的作用机制,并为其未来的临床应用提供一些证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a43d/6121076/fdc80f120b28/fphar-09-00955-g0001.jpg

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