双环醇对单侧输尿管梗阻模型大鼠肾间质骨形态发生蛋白-7表达的影响

The effect of bicyclol on expression of bone morphogenetic protein-7 in rat with renal interstitial fibrosis

目的通过建立单侧输尿管梗阻(UUO)肾间质纤维化大鼠模型,观察双环醇对肾小管间质中骨形态蛋白-7(bone morphogenetic protein-7,BMP-7)表达的影响,探究双环醇对肾间质纤维化是否具有干预作用。方法将90只13周龄健康雄性SD大鼠按随机数字表法分为假手术组、模型组和治疗组,每组30只。3组大鼠均建立UUO肾间质纤维化大鼠模型。治疗组在术后第1天开始给予双环醇[200mg/(kg·d)]灌胃;假手术组和模型组以等量生理盐水灌胃作为对照。各组分别于手术后第7、14、21天随机处死10只大鼠,留取其梗阻侧肾组织制成病理切片,分别行HE染色与Masson染色,光镜下观察肾间质的病理变化,评定小管间质损伤及肾间质纤维化的程度;用免疫组织化学方法测定各组肾组织中BMP-7在不同时间点表达水平。结果模型组7、14、21天肾间质纤维化的相对面积分别为(13.05±1.98)%、(25.66±4.39)%、(53.14±7.34)%,而治疗组分别为(9.65±1.73)%、(16.79±2.49)%、(33.57±4.81)%,治疗组较模型组肾间质纤维化的相对面积明显降低,差异有显著性(P<0.05)。术后7、14、21天模型组肾组织BMP-7的相对表达分别为0.253±0.023、0.158±0.067、0.050±0.029,而治疗组分别为0.291±0.034、0.245±0.064、0.182±0.008;治疗组肾组织中BMP-7的表达均较模型组升高,差异有显著性(P<0.05)。结论双环醇对UUO模型大鼠肾间质纤维化具有显著的改善作用,其机制可能与促进BMP-7表达上调有关。

Objective The purpose of this study is to explore the effects of bicyclol on the renal interstitial fibrosis（RIF） in rats with tubulointerstitial fibrosis induced unilateral ureteral obstruction（UUO）,and to observe the effects of bicyclol on the expression of bone morphogenetic protein-7.Method Ninety healthy Sprague-Dauley（SD） male rats,aged 13 weeks,were randomly divided into shamoperated group（n=30）,model group（n=30）and treated group（n=30）.Renal tubulointerstitial fibrosis model was established via unilateral ureteral obstruction（UUO）.Teated group was intragastric administration（ia） at bicyclol 200mg/kg once a day,sham-operated group and model group were intragastric administrated at identical voluminal normal saline.In each group,ten rats were chosen randomly to be killed at the 7d,14 d and 21 d after operation for histological examination of kidney tissue.The whole structure was observe by naked eye and the renal tubulointerstitial damage and interstitial fibrosis was examined by routine hematoxylin and eosin（HE） and Masson staining under microscope.The expression of BMP-7 in renal tissue were determined with immunohistochemical method.Result HE and Masson staining displayed that there were no predominant pathological changes in sham-operated group.The renal tubulointerstitial damage of treated group was obviously slighter than model group at every observation time.The relative area of RIF at the 7d,14 d and 21 d after operation in model group separately were（13.05±1.98）%、（25.66±4.39）%、（53.14±7.34）%,but the treated group were（9.65±1.73）%、（16.79±2.49）%、（33.57±4.81）%.So the relative area of RIF in the treated group was lower than it in the model group.The difference had statistic significance.（P〈0.05）.The relative expression of BMP-7 at the 7d,14 d and 21 d after operation in model group separately were 0.253＋0.023、0.158＋0.067、0.050＋0.029,and the treated group were 0.291＋0.034、0.245＋0.064、0.182＋0.008.So the expression of BMP-7 in treated group was higher than it in model group.The difference had statistic significance.Conclusion Bicyclol has the predominant improve effect to the renal tubulointerstitial fibrosis in UUO rats,which maybe though the promote by up-regulating the expression of HGF and BMP-7.