Sun Si-Fan, Zhao Ting-Ting, Zhang Hao-Jun, Huang Xiao-Ru, Zhang Wei-Ku, Zhang Lei, Yan Mei-Hua, Dong Xi, Wang Hua, Wen Yu-Min, Pan Xin-Ping, Lan Hui Yao, Li Ping
Graduate School of Peking Union Medical College, Chinese Academy of Medical Science, Peking Union Medical College, Beijing, China.
Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
Clin Exp Pharmacol Physiol. 2015 Jun;42(6):662-70. doi: 10.1111/1440-1681.12402.
Inflammation, fibrosis, and lipid disorder are essential promoters in the pathogenesis of diabetic kidney injury in diabetes mellitus type 2. Berberine (BBR) has been reported to have beneficial effects on diabetic nephropathy, but its action mechanism is still unclear. The present study was designed to elucidate the therapeutic mechanism of BBR in a type 2 diabetic nephropathy rat model induced by a high-fat diet and low-dose streptozotocin injection. The diabetic rats were treated with or without BBR by gavage for 20 weeks and examined by serology, 24-h albuminuria, histology, immunohistochemistry, and molecular analyses. Results showed that treatment with BBR significantly reduced serum levels of blood glucose and lipids, inhibited urinary excretion of albumin, and attenuated renal histological injuries in diabetic rats. Berberine treatment also inhibited renal inflammation, which was associated with inactivation of nuclear factor kappa-light-chain-enhancer of activated B-cell signalling. As a result, the upregulation of pro-inflammatory cytokines (interleukin-1β, tumour necrosis factor-α) and chemokine (monocyte chemotactic protein-1) was blocked. In addition, BBR treatment also inactivated transforming growth factor-β/Smad3 signalling and suppressed renal fibrosis, including expression of fibronectin, collagen I, and collagen IV. The present study reveals that BBR is a therapeutic agent for attenuating type 2 diabetic nephropathy by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cell-driven renal inflammation and transforming growth factor-β/Smad3 signalling pathway.
炎症、纤维化和脂质紊乱是2型糖尿病患者糖尿病肾损伤发病机制中的重要促进因素。据报道，黄连素（BBR）对糖尿病肾病具有有益作用，但其作用机制仍不清楚。本研究旨在阐明BBR对高脂饮食联合低剂量链脲佐菌素注射诱导的2型糖尿病肾病大鼠模型的治疗机制。对糖尿病大鼠进行为期20周的灌胃BBR治疗或不治疗，并通过血清学、24小时蛋白尿、组织学、免疫组织化学和分子分析进行检测。结果显示，BBR治疗显著降低了糖尿病大鼠的血糖和血脂水平，抑制了白蛋白尿排泄，并减轻了肾脏组织学损伤。黄连素治疗还抑制了肾脏炎症，这与活化B细胞的核因子κB轻链增强子信号失活有关。结果，促炎细胞因子（白细胞介素-1β、肿瘤坏死因子-α）和趋化因子（单核细胞趋化蛋白-1）的上调被阻断。此外，BBR治疗还使转化生长因子-β/Smad3信号失活，并抑制了肾脏纤维化，包括纤连蛋白、I型胶原和IV型胶原的表达。本研究表明，BBR是一种通过抑制活化B细胞核因子κB轻链增强子驱动的肾脏炎症和转化生长因子-β/Smad3信号通路来减轻2型糖尿病肾病的治疗药物。
