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黄芪六一汤治疗糖尿病肾病的效果及其六种活性成分在正常与糖尿病肾病小鼠模型中的组织分布差异

Effects of Huangqi Liuyi Decoction in the Treatment of Diabetic Nephropathy and Tissue Distribution Difference of its Six Active Constituents Between Normal and Diabetic Nephropathy Mouse Models.

作者信息

Wang Qun, Shi Ya, Wu Zengguang, Song Xinli, Luo Jinfang, Yang Hong, Chen Xiaolan, Liu Xingde

机构信息

Guizhou University of Traditional Chinese Medicine, Huaxi University Town, Guiyang, China.

出版信息

Front Pharmacol. 2022 Jun 21;13:934720. doi: 10.3389/fphar.2022.934720. eCollection 2022.

Abstract

The purpose of this study was to investigate the effects of Huangqi Liuyi decoction extract (HQD) on diabetic nephropathy (DN), and the tissue distribution difference of six main active ingredients of HQD between normal and DN mouse models. DN mice were administered HQD for 12 weeks to investigate its efficacy in the treatment of DN. Liquid chromatography-tandem mass-spectrometry (HPLC-MS/MS) was used to analyze the tissue distribution of the six active ingredients of HQD in normal and DN mice, including astragaloside IV, calycosin-7-O-β-D-glucoside, calycosin glucuronide, ononin, formononetin, and glycyrrhizic acid. DN mice treated with HQD showed significantly decreased fasting blood glucose (FBG), 24-h urinary protein (24 h U-Alb), blood urea nitrogen (BUN), serum creatinine (Scr), and triglyceride levels (TG) ( 0.05). Moreover, there were no significant differences in pharmacodynamics between HQD and Huangqi Liuyi decoction. Treated mice also had decreased expression of collagen I, ɑ-smooth muscle actin (ɑ-SMA), and vimentin; and upregulated expression of E-cadherin in their kidneys. Compared to normal mice, distributions of the six ingredients in the liver, heart, spleen, lungs, kidneys, stomach, small intestine, brain, and muscle of DN mice were different. The results indicated that the HQD could be used for the treatment of DN and to improve renal function. The pathological state of diabetic nephropathy may affect tissue distribution of HQD active ingredients in mice.

摘要

本研究旨在探讨黄芪六一汤提取物(HQD)对糖尿病肾病(DN)的影响,以及HQD六种主要活性成分在正常小鼠和DN小鼠模型中的组织分布差异。给DN小鼠灌胃HQD 12周,以研究其对DN的治疗效果。采用液相色谱-串联质谱法(HPLC-MS/MS)分析HQD六种活性成分在正常小鼠和DN小鼠体内的组织分布,这六种成分包括黄芪甲苷IV、毛蕊异黄酮葡萄糖苷、毛蕊异黄酮葡萄糖醛酸苷、芒柄花苷、芒柄花素和甘草酸。用HQD治疗的DN小鼠空腹血糖(FBG)、24小时尿蛋白(24 h U-Alb)、血尿素氮(BUN)、血清肌酐(Scr)和甘油三酯水平(TG)显著降低(P<0.05)。此外,HQD与黄芪六一汤在药效学方面无显著差异。治疗后的小鼠肾脏中I型胶原蛋白、α-平滑肌肌动蛋白(α-SMA)和波形蛋白的表达也降低,E-钙黏蛋白的表达上调。与正常小鼠相比,六种成分在DN小鼠肝脏、心脏、脾脏、肺脏、肾脏、胃、小肠、脑和肌肉中的分布存在差异。结果表明,HQD可用于治疗DN并改善肾功能。糖尿病肾病的病理状态可能影响HQD活性成分在小鼠体内的组织分布。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa04/9253459/9c4996fa67db/fphar-13-934720-g001.jpg

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