Chen Yong, Lin Xiaohui, Zheng Yanfang, Yu Wenzhen, Lin Fan, Zhang Jieping
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China.
Evid Based Complement Alternat Med. 2021 Sep 30;2021:9931983. doi: 10.1155/2021/9931983. eCollection 2021.
mixture (DMix) is an effective treatment for diabetic nephropathy (DN), but the molecular mechanism underlying its action remains unclear. In this study, we investigated whether DMix regulates the transforming growth factor-1 (TGF-1)/Smads signal transduction pathway. Twenty-four db/db mice were randomly divided into three groups: the model, DMix, and gliquidone groups, while eight db/m mice were selected as the normal control group. The drug was administered by continuous gavage for 8 weeks. Body weight (BW), kidney weight (KW), kidney index, fasting blood glucose (FBG), blood lipid, 24-hour urinary albumin excretion rate, blood urea nitrogen, and serum creatinine levels were measured. Pathological changes in the renal tissue were observed under a light microscope. Real-time quantitative PCR and immunohistochemical staining were used to detect the mRNA and protein expression levels of TGF-1 and alpha-smooth muscle actin (-SMA), respectively, in renal tissues. TGF-1, Smad2, p-Smad2, Smad3, p-Smad3, and -SMA expression levels were measured using western blotting. The results showed that DMix significantly reduced the FBG level, BW, KW, and blood lipid level and improved renal function in db/db mice. Histopathology showed that DMix alleviated glomerular mesangial cell proliferation and renal interstitial fibrosis in db/db mice. Additionally, DMix reduced the protein and mRNA expression levels of TGF-1 and -SMA and inhibited Smad2 and Smad3 phosphorylation. We conclude that DMix may inhibit renal fibrosis and delay the progression of DN by regulating the TGF-1/Smads signaling pathway.
复方制剂（DMix）是治疗糖尿病肾病（DN）的一种有效疗法，但其作用的分子机制仍不清楚。在本研究中，我们调查了DMix是否调节转化生长因子-β1（TGF-β1）/Smads信号转导通路。将24只db/db小鼠随机分为三组：模型组、DMix组和格列喹酮组，同时选取8只db/m小鼠作为正常对照组。通过连续灌胃给药8周。测量体重（BW）、肾脏重量（KW）、肾脏指数、空腹血糖（FBG）、血脂、24小时尿白蛋白排泄率、血尿素氮和血清肌酐水平。在光学显微镜下观察肾组织的病理变化。分别采用实时定量PCR和免疫组织化学染色检测肾组织中TGF-β1和α-平滑肌肌动蛋白（α-SMA）的mRNA和蛋白表达水平。采用蛋白质免疫印迹法检测TGF-β1、Smad2、磷酸化Smad2、Smad3、磷酸化Smad3和α-SMA的表达水平。结果显示，DMix显著降低db/db小鼠的FBG水平、BW、KW和血脂水平，并改善肾功能。组织病理学显示，DMix减轻db/db小鼠的肾小球系膜细胞增殖和肾间质纤维化。此外，DMix降低TGF-β1和α-SMA的蛋白和mRNA表达水平，并抑制Smad2和Smad3磷酸化。我们得出结论，DMix可能通过调节TGF-β1/Smads信号通路抑制肾纤维化并延缓DN的进展。
