Wang Mei-Zi, Yue Li-Jun, Wan Yi-Gang, Huang Huang, Wu Wei, Tu Yue, Liu Bu-Hui, Fang Qi-Jun, Yuan Can-Can, Wang Jie, Li Huan, Wan Zi-Yue
Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine Nanjing 210008, China.
Department of Traditional Chinese Medicine, Nanjing Drum Tower Hospital,The Affiliated Hospital of Medical School of Nanjing University Nanjing 210008, China.
Zhongguo Zhong Yao Za Zhi. 2021 Sep;46(17):4471-4479. doi: 10.19540/j.cnki.cjcmm.20210524.406.
This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.
本研究探讨了现代经典方剂加味葛根芩连汤方(SGDF)抗糖尿病肾病(DKD)的体内效应及机制。将60只大鼠随机分为正常组、模型组、SGDF组和罗格列酮(ROS)组。采用高脂饮食、单侧肾切除及腹腔注射链脲佐菌素(STZ)三种方法建立改良DKD大鼠模型。造模后,四组大鼠分别每天经口灌胃给予双蒸水、SGDF混悬液和ROS混悬液。给药第6周结束时,处死所有大鼠,收集尿液、血液和肾脏组织,随后检测大鼠一般状况、尿液和血液生化指标、肾小球硬化相关指标、足细胞焦亡标志物、胰岛素抵抗(IR)相关指标以及胰岛素受体底物(IRS)1/磷脂酰肌醇-3-激酶(PI3K)/丝氨酸苏氨酸激酶(Akt)信号通路中的关键分子。结果显示,SGDF和ROS改善了DKD模型大鼠的一般状况、部分肾功能指标和肾小球硬化,且不影响血糖(BG)。此外,它们改善了足细胞焦亡标志物的表达特征和水平,减轻了IR,并不同程度上调了IRS1/PI3K/Akt通路中关键分子的蛋白表达水平。总之,与ROS相似,SGDF在体内通过靶向多个靶点缓解DKD。具体而言,它通过减轻足细胞焦亡和IR发挥治疗作用。本研究初步为基于SGDF研发治疗DKD的新药提供了药理学证据。