肾络通对肾间质纤维化模型小鼠肾小管上皮细胞表型转化的影响  

Impact of Shenluotong (肾络通) on Phenotypic Transformation of Renal Tubular Epithelial Cells in Renal Interstitial Fibrosis Model Mice

作　　者：孙东云[1,2] 王筝[2,3] 王香婷[2,3] 王聪慧[1] 王淼[1] 梁丽娟[1] 许庆友[1,2,3] 

机构地区：[1]河北医科大学研究生院 [2]河北中医学院中西医结合学院 [3]河北省中西医结合肝肾病重点实验室

出　　处：《中医杂志》2016年第18期1593-1597,共5页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81273684;81473652);河北省自然科学基金(C2011206042;H2015423009)

摘　　要：目的探讨肾络通治疗肾间质纤维化的可能作用机制。方法纯系C57BL/6J野生小鼠(WT)及肾上腺髓质素基因敲除杂合子小鼠(AMKO)随机分为假手术组、模型组、依普利酮组及肾络通组,每组5只。除假手术组外,其余各组结扎左侧输尿管复制肾间质纤维化小鼠模型。依普利酮组给予依普利酮100 mg/(kg·d)加入饲料喂养,肾络通组给予肾络通溶液26 g/(kg·d)灌胃,假手术组和模型组给予蒸馏水0.3 ml灌胃,共10天。HE、Masson染色观察各组小鼠梗阻侧肾组织病理改变;免疫组化法及Western Blot法检测肾组织α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)、肾上腺髓质素(ADM)的表达;检测血肌酐(Scr)、尿素氮(BUN)水平。结果 WT及AMKO小鼠各组血Scr和BUN含量比较差异均无统计学意义(P>0.05)。肾脏病理结果显示,模型组肾小管扩张、上皮细胞坏死,肾间质大量炎性细胞浸润,胶原组织沉积显著增多,依普利酮组和肾络通组可明显抑制间质炎性细胞浸润及胶原沉积。与本鼠种假手术组比较,WT模型组和AMKO模型组α-SMA、TGF-β1表达明显升高,而ADM表达明显降低(P<0.01)。与本鼠种模型组比较,依普利酮组和肾络通组α-SMA、TGF-β1表达明显降低,而ADM表达明显升高(P<0.05或P<0.01)。两鼠种之间比较,AMKO假手术组、模型组、依普利酮组、肾络通组ADM表达均低于相应的WT小鼠组(P<0.05或P<0.01)。结论肾络通可能通过上调ADM表达,降低α-SMA、TGF-β1表达,从而抑制肾小管上皮细胞表型转化,减轻了肾脏病理损伤。Objective To explore the possible mechanism of Shenluotong in treating renal interstitial fibrosis.Methods Pure strain of wild mice of C57 BL /6J（ WT） and heterozygous mice with adrenal medulla gene knockout（ AMKO） were randomized into a sham operation group,a model group,an eplerenone group and a Shenluotong group,with 5 mice in each group. Mice in each group were taken left ureter ligation to establish renal interstitial fibrosis mice models except those in the sham operation group. The eplerenone group was fed with fodder added with100 mg /（ kg · d） of eplerenone,the Shenluotong group was given 26 g /（ kg · d） of Shenluotong solution by gavage,the sham operation group and the model group were given 0. 3 ml of distilled water by gavage,all for 10 days. Pathological changes of renal tissue of obstructive side in all groups were examined with hematoxylin and eosin（ HE） stain and Masson stain. The expressions ofα-smooth muscle actin（ α-SMA）,transforming growth factor-β1（ TGF-β1） and adrenomedulin（ ADM） in renal tissue were detected with immunohistochemical method and Western Blot method. The level of serum creatinine（ Scr） and blood urine nitrogen（ BUN） were detected. Results There was no significant difference in levels of Scr and BUN in WT and AMKO mice between all groups（ P〈 0. 05）. Renal pathologic findings showed that there was tubular ectasia,epithelial cell necrosis and a large number of inflammatory cell infiltration in renal interstitial,and that collagen deposition increased significantly in the model group. Inflammatory cell infiltration in renal interstitial and collagen deposition was inhibited in the eplerenone group and the Shenluotong group. Compared with the same mice species in the sham operation group,the expression levels ofα-SMA and TGF-β1 increased,while the expression level of ADM decreased in the WT model group and the AMKO model group（ P〈 0. 01）. Compared with the same mice species in the model group,the expression levels ofα-SMA

关 键 词：肾间质纤维化 肾络通 肾小管上皮细胞表型转化 Α-平滑肌肌动蛋白 转化生长因子-β1 肾上腺髓质素 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]