Wei Ming-Gang, He Wei-Ming, Lu Xun, Ni Li, Yang Yan-Yu, Chen Lin, Xiong Pei-Hua, Sun Wei
The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, Jiangsu 210029, China.
Evid Based Complement Alternat Med. 2016;2016:5031890. doi: 10.1155/2016/5031890. Epub 2016 Jun 14.
JiaWeiDangGui (JWDG) decoction has anti-inflammatory and antifibrotic effects, which is used widely for the treatment of various kidney diseases. In previous studies, we have found that JWDG decoction can reduce the quantity of proteinuria, but the mechanism was unknown. Here, we studied the protective effect of JWDG decoction in adriamycin-induced nephropathy on rat. JWDG decoction, at 10 mL/kg/d, 20 mL/kg/d, and 40 mL/kg/d, was orally administered daily for 12 weeks. Therapeutic effects and mechanisms were further examined. The kidney function related biochemical indexes were measured by automatic biochemistry analyzer. The pathomorphological changes were observed using light and transmission electron microcopies. The proteins expressions of podocin, nephrin, collagen IV, and fibronectin (FN) were examined by immunohistochemical staining, and key proteins involved in TGF-β/Smad signaling were evaluated by RT-PCR and western blotting. Compared with vehicle-treated controls, JWDG decoction decreased the quantity of proteinuria; reduced glomerulosclerotic lesions induced by ADR; and preserved the expression of podocin and nephrin. JWDG decoction also inhibited the expression of the collagen IV, FN, and fibrogenic TGF-β. Further studies revealed that inhibition of renal fibrosis was associated with the blockade of TGF-β/Smad signaling and downregulation of snail expression dose dependently. JWDG decoction prevents proteinuria production, podocyte dysfunction, and kidney injury in adriamycin nephropathy by inhibiting TGF-β/Smad signaling.
加味当归（JWDG）汤具有抗炎和抗纤维化作用，广泛用于治疗各种肾脏疾病。在先前的研究中，我们发现JWDG汤可以减少蛋白尿的量，但其机制尚不清楚。在此，我们研究了JWDG汤对阿霉素诱导的大鼠肾病的保护作用。将JWDG汤以10 mL/kg/d、20 mL/kg/d和40 mL/kg/d的剂量每日口服给药12周。进一步检测其治疗效果和机制。使用自动生化分析仪测量肾功能相关的生化指标。通过光镜和透射电镜观察病理形态学变化。通过免疫组织化学染色检测足细胞裂孔素、nephrin、IV型胶原和纤连蛋白（FN）的蛋白表达，并通过RT-PCR和western blotting评估TGF-β/Smad信号通路中涉及的关键蛋白。与溶剂处理的对照组相比，JWDG汤减少了蛋白尿的量；减轻了阿霉素诱导的肾小球硬化病变；并保留了足细胞裂孔素和nephrin的表达。JWDG汤还抑制了IV型胶原、FN和促纤维化TGF-β的表达。进一步的研究表明，抑制肾纤维化与TGF-β/Smad信号通路的阻断和蜗牛蛋白表达的剂量依赖性下调有关。JWDG汤通过抑制TGF-β/Smad信号通路预防阿霉素肾病中的蛋白尿产生、足细胞功能障碍和肾损伤。
