Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats.
Therapeutic Effects of Tangshen Formula on Diabetic Nephropathy in Rats.
复制标题
糖肾方对大鼠糖尿病肾病的治疗作用
DOI：
10.1371/journal.pone.0147693
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li P
中科院分区：
文献类型：
--
作者：
Zhao T;Sun S;Zhang H;Huang X;Yan M;Dong X;Wen Y;Wang H;Lan HY;Li P
目的炎症和纤维化是2型糖尿病肾病(DN)发病的重要促进剂。本研究观察了中药糖参方(TSF)对糖尿病肾病的抗炎、抗纤维化作用。研究设计与方法采用高脂饲料喂养小剂量链脲佐菌素建立的2型糖尿病大鼠模型，观察TSF对糖尿病肾病的保护作用。TSF混悬液为0.5%CMC-Na溶液，按1.67g/kg体重/天灌胃给药。探讨TSF对糖尿病肾损伤的治疗作用及其机制。结果TSF治疗20周可明显抑制尿白蛋白排泄和肾脏组织学损伤，从而减轻糖尿病肾病。这些有益的作用与抑制NF-κB信号转导有关，从而阻断了2型糖尿病肾病大鼠促炎症细胞因子(IL-1β、α)、趋化因子(MCP-1)的上调和巨噬细胞的浸润。此外，丹参还可抑制转化生长因子-β/Smad3信号通路，从而抑制肾纤维化，包括纤维连接蛋白、I型胶原和IV型胶原的表达。进一步研究表明，TSF对糖尿病肾病转化生长因子-β/Smad3和核因子-SmadB信号的抑制作用与抑制Smad7依赖S-κ2的泛素降解有关。结论TSF对大鼠2型糖尿病具有一定的治疗潜力。通过阻断Smad7降解途径，阻断NF-κB介导的肾脏炎症和转化生长因子-β/Smad3介导的肾脏纤维化，可能是其抑制2型糖尿病肾病的机制之一。
Objective Inflammation and fibrosis are essential promoters in the pathogenesis of diabetic nephropathy (DN) in type 2 diabetes. The present study examined the anti-inflammation and anti-fibrosis effect of Tangshen Formula (TSF), a traditional Chinese medicine, on DN. Research Design and Methods Protective role of TSF in DN was examined in a rat model of type 2 DN that was established by high-fat diet-fed and low-dose-streptozotocin injection. TSF was suspended in 0.5% CMC-Na solution and delivered by oral gavage at a dosage of 1.67g/Kg body weight/day. The therapeutic effects and mechanisms of TSF on diabetic kidney injury were examined. Results We found that TSF treatment for 20 weeks attenuated DN by significantly inhibiting urinary excretion of albumin and renal histological injuries. These beneficial effects were associated with an inactivation of NF-κB signaling, thereby blocking the upregulation of pro-inflammatory cytokines (IL-1β, TNFα), chemokine (MCP-1), and macrophage infiltration in the TSF-treated rats with type 2 DN. In addition, TSF treatment also inactivated TGF-β/Smad3 signaling and therefore suppressed renal fibrosis including expressions of fibronectin, collagen I, and collagen IV. Further studies revealed that the inhibitory effect of TSF on TGF-β/Smad3 and NF-κB signaling in DN was associated with inhibition of Smurf2-dependent ubiquitin degradation of Smad7. Conclusions The present study reveals that TSF has therapeutic potential for type 2 DN in rats. Blockade of NF-κB-driven renal inflammation and TGF-β/Smad3-mediated renal fibrosis by preventing the Smurf2-mediated Smad7 degradation pathway may be mechanisms through which TSF inhibits type 2 DN.