Jin Di, Zhao Yunyun, Sun Yuting, Xue Jiaojiao, Li Xiangyan, Wang Xiuge
The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, China.
College of Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jinlin, China.
Biomed Pharmacother. 2023 Apr;160:114340. doi: 10.1016/j.biopha.2023.114340. Epub 2023 Feb 3.
Renal fibrosis, an important pathological change in the development of diabetic kidney disease (DKD), urgently needs new treatment methods clinically. The Jiedu Tongluo Baoshen (JTBF) formula was created based on the theory of toxic damage to the kidney collaterals, and a variety of active ingredients in JTBF have inhibitory effects on epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM). In this study, the Ultra Performance Liquid Chromatography (UPLC) was employed to analyze the effective ingredients in the JTBF formula. After screening in the PubChem database, we identified 94 active compounds of JTBF and predicted the SIRT1 pathway as potential targets through network pharmacology. In addition, in the high fat diet (HFD)+Streptozocin (STZ)-induced DKD rat model and high glucose (HG)-induced NRK-52E cell model, JTBF treatment activates the phosphorylation of LKB1 and AMPK and enhances the autophagy activity of NRK-52E cells, thereby reducing the accumulation of EMT and ECM. These results have been confirmed in vivo and in vitro experiments. JTBF enhances the autophagy activity of renal tubular epithelial cells and inhibits the progression of DKD renal fibrosis by activating the SIRT1/LKB1/AMPK signal pathway. This study provides new insights into the molecular mechanism of JTBF to prevent and treat DKD renal fibrosis.
肾纤维化是糖尿病肾病（DKD）发展过程中的一种重要病理变化，临床上迫切需要新的治疗方法。解毒通络保肾（JTBF）方基于肾络毒损理论创制，JTBF中的多种活性成分对上皮-间质转化（EMT）和细胞外基质（ECM）具有抑制作用。本研究采用超高效液相色谱（UPLC）分析JTBF方中的有效成分。在PubChem数据库中筛选后，我们鉴定出JTBF的94种活性化合物，并通过网络药理学预测SIRT1通路为潜在靶点。此外，在高脂饮食（HFD）+链脲佐菌素（STZ）诱导的DKD大鼠模型和高糖（HG）诱导的NRK-52E细胞模型中，JTBF治疗可激活LKB1和AMPK的磷酸化，增强NRK-52E细胞的自噬活性，从而减少EMT和ECM的积累。这些结果在体内和体外实验中均得到证实。JTBF通过激活SIRT1/LKB1/AMPK信号通路增强肾小管上皮细胞的自噬活性，抑制DKD肾纤维化的进展。本研究为JTBF防治DKD肾纤维化的分子机制提供了新的见解。
