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普瑞丹通过调节 mTOR/S6K1/SREBP-1c 信号通路缓解 2 型糖尿病老龄大鼠非酒精性脂肪肝病。

Purendan alleviates non-alcoholic fatty liver disease in aged type 2 diabetic rats via regulating mTOR/S6K1/SREBP-1c signaling pathway.

机构信息

School of Pharmacy, Minzu University of China, Beijing, PR China; Key Laboratory of Ethnomedicine (Minzu University of China), Ministry of Education, Beijing, PR China.

出版信息

Biomed Pharmacother. 2022 Apr;148:112697. doi: 10.1016/j.biopha.2022.112697. Epub 2022 Feb 14.

Abstract

Older people are more likely to develop insulin resistance and lipid metabolism disorders. Purendan (PRD) is a clinically verified traditional Chinese medicine compound, which plays an obvious role in regulating lipid metabolism disorder and improving insulin sensitivity. Our study aimed to investigate the efficacy and mechanism of PRD on aged type 2 diabetes mellitus (T2DM) complicated with non-alcoholic fatty liver disease (NAFLD) rats. Sprague-Dawley rats (13 months) were fed with high-fat diet (HFD) and injected with low-dose STZ to replicate T2DM model. PRD was treated at three concentrations with metformin as a positive control. After administration, blood and liver tissue samples were collected to measure glucose metabolism indexes such as serum glucose and insulin, as well as lipid metabolism indexes such as TC, TG, LDL, HDL and FFA. Liver fat accumulation was observed by HE staining and oil red O staining. And protein expression levels of mTOR, p-mTOR, S6K1, p-S6K1 and SREBP-1c were detected by western blot. After PRD treatment, not only the insulin sensitivity and insulin resistance were significantly improved, but also the TC, TG, LDL, FFA, AST and ALT in serum and the lipid accumulation in liver tissue were significantly decreased. Moreover, PRD significantly down-regulated the expression of p-mTOR, p-S6K1 and SREBP-1c in liver tissues. In conclusion, PRD can alleviate NAFLD in aged T2DM rats by inhibiting the mTOR /S6K1/ SREBP-1c pathway.

摘要

老年人更容易出现胰岛素抵抗和脂质代谢紊乱。蒲丹(PRD)是一种经过临床验证的中药复方,在调节脂质代谢紊乱和改善胰岛素敏感性方面具有明显作用。我们的研究旨在探讨 PRD 对老年 2 型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)大鼠的疗效和作用机制。SD 大鼠(13 个月)给予高脂饮食(HFD)并注射小剂量 STZ 复制 T2DM 模型。PRD 以三个浓度与二甲双胍作为阳性对照进行治疗。给药后,采集血液和肝组织样本,测量血糖代谢指标如血清葡萄糖和胰岛素,以及脂质代谢指标如 TC、TG、LDL、HDL 和 FFA。通过 HE 染色和油红 O 染色观察肝脂肪堆积。通过 Western blot 检测 mTOR、p-mTOR、S6K1、p-S6K1 和 SREBP-1c 的蛋白表达水平。PRD 治疗后,不仅胰岛素敏感性和胰岛素抵抗明显改善,而且血清中 TC、TG、LDL、FFA、AST 和 ALT 以及肝组织中的脂质堆积也明显减少。此外,PRD 显著下调了肝组织中 p-mTOR、p-S6K1 和 SREBP-1c 的表达。总之,PRD 通过抑制 mTOR/S6K1/SREBP-1c 通路可以缓解老年 T2DM 大鼠的 NAFLD。

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