肾络通煎剂对梗阻性肾病大鼠肾间质纤维化的影响

Effect of Shenluotong Decoction on Renal Interstitial Fibrosis in Rats with Obstructive Nephropathy

目的探讨肾络通煎剂对梗阻性肾病大鼠血清醛固酮、单核细胞趋化蛋白-1(monocyte chemotactic protein 1,MCP-1)、α平滑肌激动蛋白(α-smooth muscle protein,α-SMA)、核因子κB(nuclear factor-κB,NF-κB)表达的影响,探讨肾络通煎剂改善肾间质纤维化的初步机制。方法将48只健康Wistar大鼠随机分为假手术组(12只)、造模组(36只)。先采用单侧输尿管结扎(unilateral ureteral obstruction,UUO)手术复制肾间质纤维化模型,再将造模成功大鼠随机分为模型组、西药组和中药组,每组12只。西药组(依普利酮)按照100 mg/(kg·d)剂量加入饲料中,中药组按照26 g/(kg·d)的剂量入水瓶饮用,假手术组和模型组给予等量生理盐水饮用,每天1次。给药10天后摘取梗阻侧肾脏,观察肾脏病理形态学,检测血清醛固酮、MCP-1含量,肾组织MCP-1、α-SMA、NF-κB mRNA或蛋白表达。结果与假手术组比较,模型组大鼠肾组织中大量炎性细胞浸润,胶原沉积显著增加,血清醛固酮及MCP-1含量显著升高(P<0.01),MCP-1核酸和蛋白表达水平明显上调(P<0.01),α-SMA及NF-κB蛋白表达水平明显升高(P<0.01)。与模型组比较,西药组及中药组炎性细胞浸润及胶原沉积均减轻,血清MCP-1含量降低,MCP-1 mRNA及蛋白表达水平降低(P<0.01),α-SMA及NF-κB蛋白表达水平明显降低(P<0.01),同时,中药组血清醛固酮含量减少(P<0.01)。结论梗阻性肾病模型鼠肾组织炎症损伤可促进肾间质纤维化。肾络通煎剂可通过减少血清醛固酮及MCP-1含量,下调肾组织MCP-1、NF-κB表达,抑制α-SMA表达,减轻肾间质纤维化。

Objective To observe the effect of Shenluotong Decoction （SD） on serum levels of aldosterone, monocyte chemoattractant protein-1 （MCP-1）, α-smooth muscle protein （α-SMA）, and nuclear factor-κB （NF-κB） in obstructive nephropathy rats, and to explore the initial mechanism of SD for inhibiting renal interstitial fibrosis. Methods Totally 48 healthy Wistar rats were randomly divided into the sham-operation group （n =12） and the model group （n =36）. Renal interstitial fibrosis rat model was established by unilateral ureteral obstruction （UUO）. After successful modeling, 36 rats were randomly divided into the model group, the Chinese medicine group, and the Western medicine group, 12 in each group. Eplerenone was added in the forage at the daily dose of 100 mg/kg for rats in the Western medicine group. Chinese medicine was added in the forage at the daily dose of 26 g/kg for rats in the Chinese medi- cine group. Equal volume of normal saline was administered to rats in the sham-operation group and the model group. All medication was performed once daily. The obstructive kidneys were extracted ten daysafter medication. The pathomorphological changes were observed. The contents of serum aldosterone and MCP-1, and the protein or mRNA expression of MCP-1, α-SMA, and NF-κB were detected. Results Compared with the sham-operation group, infiltration of a large amount of inflammatory cells and collagen deposition significantly increased, serum contents of aldosterone and MCP-1 obviously increased （P 〈 0.01 ）, the expression of MCP-1 mRNA and protein were significantly up-regulated （P 〈0.01 ）, the pro- tein expression of α-SMA and NF-κB were significantly enhanced in the model group （P 〈0.01 ）. Com- pared with the model group, infiltration of inflammatory cells and renal collagen deposition were attenua- ted in the Chinese medicine group and the Western medicine group, the serum MCP-1 level were re- duced, and the mRNA and protein expression of MCP-1 were significantly down-regulated （P 〈0.01 ）, the protein expression of （^-SMA and NF-KB were obviously inhibited （P 〈0.01 ）. At the same time, serum al- dosterone level was reduced in the Chinese medicine group （P 〈0.01 ）. Conclusions Inflammatory le- sions of the renal tissue could promote the progress of interstitial fibrosis in rats with obstructive ne- phropathy. SD could attenuate interstitial fibrosis through reducing serum contents of aldosterone and MCP-1, down-regulating MCP-1/NF-KB, and inhibiting the expression of α-SMA.