Chaihuang-Yishen granule inhibits diabetic kidney disease in rats through blocking TGF-β/Smad3 signaling.
Chaihuang-Yishen granule inhibits diabetic kidney disease in rats through blocking TGF-β/Smad3 signaling.
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DOI：
10.1371/journal.pone.0090807
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发表时间：
2014
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 TT;Zhang HJ;Lu XG;Huang XR;Zhang WK;Wang H;Lan HY;Li P
越来越多的证据表明，转化生长因子-β-1是糖尿病肾病的关键介质，Smad3正向诱导肾脏纤维化，而Smad7负向诱导肾脏纤维化。然而，通过阻断转化生长因子-β/Smad通路来治疗糖尿病肾病仍然是有限的。本研究探讨中药柴黄益肾颗粒(Chys)对糖尿病肾病的抗纤维化作用。用链脲佐菌素诱导的Wistar大鼠加速型糖尿病肾病模型，观察Chys对糖尿病肾病的保护作用。以0.56g/kg体重灌胃给予Chys，连续灌胃20周，观察Chys对糖尿病大鼠肾脏损伤的治疗作用及其可能机制。Chys治疗通过显著抑制24小时蛋白尿和进行性肾脏纤维化(包括肾小球硬化指数、肾小管间质纤维化指数)和上调细胞外基质(I、IV型胶原和纤维连接蛋白)来减轻糖尿病肾损伤，尽管血糖水平相同。进一步的研究表明，Chys治疗的糖尿病大鼠肾脏纤维化的抑制与抑制转化生长因子-Smad1/Smad3信号通路有关，如Smad7上调，但下调转化生长因子-β1、转化生长因子-β受体、Smad3的激活和β-21的表达。Chys可能是一种治疗糖尿病肾病的药物。Chys通过阻断转化生长因子-β/Smad3介导的肾脏纤维化来减轻糖尿病肾病。
Increasing evidence shows that TGF-β1 is a key mediator in diabetic nephropathy (DN) and induces renal fibrosis positively by Smad3 but negatively by Smad7. However, treatment of DN by blocking the TGF-β/Smad pathway remains limited. The present study investigated the anti-fibrotic effect of a traditional Chinese medicine, Chaihuang-Yishen granule (CHYS), on DN. Protective role of CHYS in DN was examined in an accelerated type 1 DN induced by streptozotocin in uninephrectomized Wistar rats. CHYS, at a dose of 0.56 g/kg body weight, was administered by a daily gastric gavage for 20 weeks and the therapeutic effect and potential mechanisms of CHYS on diabetic kidney injury were examined. Treatment with CHYS attenuated diabetic kidney injury by significantly inhibiting 24-h proteinuria and progressive renal fibrosis including glomerulosclerotic index, tubulointerstitial fibrosis index, and upregulation of extracellular matrix (collagen I, IV, and fibronectin), despite the same levels of blood glucose. Further studies revealed that inhibition of renal fibrosis in CHYS-treated diabetic rats was associated with inhibition of TGF-β1/Smad3 signaling as demonstrated by upregulation of Smad7 but downregulation of TGF-β1, TGF-β receptors, activation of Smad3, and expression of miRNA-21. CHYS may be a therapeutic agent for DN. CHYS attenuates DN by blocking TGF-β/Smad3-mediated renal fibrosis.
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影响因子：
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作者：
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