Ai S, Lin Y Y, Zheng J, Qiu C X, Liu Y J, Lin X
People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, China.
Key Laboratory of Integrative Kidney Disease in Fujian Province, Fuzhou, Fujian, China.
Genet Mol Res. 2016 Aug 19;15(3):gmr8131. doi: 10.4238/gmr.15038131.
Shenkangling plays a role of Yishenhuoxue effect for the treatment of children with nephrotic syndrome. The aim of this study was to investigate the effects of Shenkangling intervention on the mitogen-activated protein kinase (MAPK) pathway in rats with Adriamycin-induced nephropathy (AN) and its underlying mechanism of action. Nephrosis was induced in healthy Sprague-Dawley rats by doxorubicin and the rats were untreated or treated with prednisone, simvastatin, Shenkangling, or a combination thereof. Using real-time PCR, the mRNA expression levels of Chemokine (C-X-C motif) ligand 16 (CXCL16), A Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10), and ADAM17 in the renal tissues of these rats were found to be decreased by the various treatments compared to those in the untreated doxorubicin-induced nephrosis rats. To quantify the activation of the MAPK pathway, western blotting was used to detect the phosphorylation levels of MAPK pathway-associated proteins (p38, ERK1/2, SAPK/JNK) and nuclear factor (NF)-κB p65, which were reduced by the various treatments compared to those in the untreated doxorubicin-induced rats. Serum levels of transforming growth factor (TGF)-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, quantified by ELISA, were decreased by the various treatments compared to the levels in the untreated doxorubicin-induced nephrosis rats. The rats treated with prednisone, simvastatin, and Shenkangling showed the best outcome. The Chinese medicine Shenkangling that is known for nourishing the kidney and promoting blood circulation reduced urinary protein levels, increased serum albumin levels, and reduced cholesterol levels by reducing the release of CXCL16, ADAM10, ADAM17, TGF-β1, TNF-α, IL-1β, IL- 6, and other inflammatory mediators and inhibiting the activation of the MAPK signaling pathway, thereby effectively improving the state of nephropathy in AN rats. These results indicate that Shenkangling can be used clinically to treat nephropathy.
肾康灵在治疗儿童肾病综合征中具有益肾活血作用。本研究旨在探讨肾康灵干预对阿霉素诱导的肾病（AN）大鼠丝裂原活化蛋白激酶（MAPK）通路的影响及其潜在作用机制。通过阿霉素诱导健康的Sprague-Dawley大鼠发生肾病，对大鼠不进行治疗或用泼尼松、辛伐他汀、肾康灵或它们的组合进行治疗。使用实时PCR发现，与未治疗的阿霉素诱导的肾病大鼠相比，这些大鼠肾组织中趋化因子（C-X-C基序）配体16（CXCL16）、含解聚素和金属蛋白酶结构域蛋白10（ADAM10）以及ADAM17的mRNA表达水平因各种治疗而降低。为了量化MAPK通路的激活情况，采用蛋白质印迹法检测MAPK通路相关蛋白（p38、ERK1/2、SAPK/JNK）和核因子（NF）-κB p65的磷酸化水平，与未治疗的阿霉素诱导的大鼠相比，各种治疗使其降低。通过酶联免疫吸附测定法（ELISA）定量的转化生长因子（TGF）-β1、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-6的血清水平，与未治疗的阿霉素诱导的肾病大鼠相比，各种治疗使其降低。用泼尼松、辛伐他汀和肾康灵治疗的大鼠效果最佳。以补肾活血著称的中药肾康灵通过减少CXCL16、ADAM10、ADAM17、TGF-β1、TNF-α、IL-1β、IL-6等炎症介质的释放并抑制MAPK信号通路的激活，降低尿蛋白水平，提高血清白蛋白水平，降低胆固醇水平，从而有效改善AN大鼠的肾病状态。这些结果表明肾康灵可用于临床治疗肾病。
