祛毒颗粒对单侧输尿管梗阻大鼠肾间质纤维化的干预作用  

Intervene Effect of Qudu Granules on the Renal Interstitial Fibrosis in Rats with Unilateral Ureteral Obstruction

作　　者：郭兆安[1] 李敏[2] 赵鑫[2] 吴增利[2] 房婧[2] 李靖[2] 马东明[2] 于燕燕[2] 

机构地区：[1]山东中医药大学附属医院,济南250011 [2]山东中医药大学临床学院,硕士研究生济南250011

出　　处：《中国中西医结合肾病杂志》2010年第11期965-969,1038-1040,共8页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：山东省科学技术发展计划项目(No.2008GG2N02002)

摘　　要：目的:观察祛毒颗粒对单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠肾间质纤维化的干预作用,并探讨其作用机制。方法:将90只雄性Wistar大鼠随机分为5组:假手术组、模型组、尿毒清组(对照组)、祛毒颗粒低剂量组(低剂量组)、祛毒颗粒高剂量组(高剂量组),每组18只,除假手术组,其余各组用单侧输尿管梗阻法(UUO)建立肾间质纤维化动物模型,术前1天起各组给予相应浓度和剂量的药物,分别在术后第3天、7天、14天分批处死大鼠,检测大鼠尿N-已酰-β-氨基葡萄糖苷(NAG)酶、血肌酐(Scr)和尿素氮(BUN)变化,梗阻侧肾组织行HE染色和Masson染色,HE染色观察肾组织病理变化并半定量计算肾小管损伤指数(tubulointerstitial injuryindex,TII),Masson染色测定肾间质胶原面积,免疫组化法检测结缔组织生长因子(CTGF)、Ⅰ型胶原(ColⅠ)、肝细胞生长因子(HGF)、骨形成蛋白(BMP)-7在肾组织的表达。结果:与模型组及对照组相比,祛毒颗粒能明显降低UUO大鼠术后14d的尿NAG酶、Scr、BUN(P<0.05);对梗阻侧肾组织HE染色进行TII评分发现,不同时间点,2个试验组大鼠肾小管损伤指数低于模型组和对照组(P<0.05～0.01);Masson染色测定肾间质胶原面积,2个实验组大鼠肾间质胶原面积少于模型组和对照组(P<0.05～0.01);免疫组化法染色发现,与模型组和对照组相比,2个试验组大鼠CTGF、ColⅠ在肾组织的表达下调(P<0.05),HGF、BMP-7在肾脏组织的表达上调(P<0.05)。结论:祛毒颗粒具有改善肾间质纤维化的作用,其机制可能与下调UUO大鼠致纤维化因子CTGF、ColⅠ在肾脏的表达,上调抗纤维化因子HGF、BMP-7在肾脏的表达有关。Objective：To study the intervene effect of qudu granules on the renal interstitial fibrosis in rats with unilateral ureteral obstruction（UUO） and explore its renoprotcetive mechanism.Methods：90 male Wistar rats were divided randomly into five groups（n=18）：the sham operation group,the model group,Niao Duqing granules group （control group）,the low-dosage of Qudu granules group （low dosage group） and high dosage of Qudu granules group （high dosage group）.Except the rats in the sham operation group,the other ratswere established renal interstitial fibrosis animal model by UUO.Medicine was given to each group according to the designed concentration and dosage from the day before the operation.The rats were killed on the third,seventh and fourtheenth day in batches respectively.N-actely-β-D-glucosaminidase （NAG） in the urine,Serum creatinine（Scr）,blood urea nitrogen（BUN） were measured.Histological change in the obstructed kidney was examined by HE stain and Masson stain.The protein expression of Connective tissue growth factor（CTGF）,type Ⅰ collagen（ColⅠ）,Hepatocyte growth factor（HGF）and Bone Morphogenic Protein 7 （BMP-7） in obstructed kidney tissues were detected by ELISA respectively.Results：Qudu granules could significantly reduce urinary NAG enzyme,improve the creatinine and urea nitrogen,decrease TII and area of renal interstitial collapen,down-regulate the expression of CTGF in the renal tissue,inhibit the ColⅠin renal tissue,increase the expression of the anti-fibrosis factors HGF、BMP-7 in the kidney and improve the renal interstitial fibrosis.The efficacy of Qudu granules was better than that of Niao Duqing granules.Conclusion：Qudu granules has the function of protecting the renal function of rats with renal interstitial fibrosis,reducing the NAG enzyme in urine,the renal pathological damage.Its mechanism may be related with down-regulating the expression of CTGF、ColⅠin the kidney,increasing the expression of the anti-fibrosis factors,such as

关 键 词：祛毒颗粒 肾间质纤维化 结缔组织生长因子 肝细胞生长因子 骨形成蛋白 

分 类 号：R285.5[医药卫生—中药学]