紧密连接蛋白在高尿酸血症致大鼠肾间质纤维化肾组织的表达及非布司他的干预作用  

Expression of tight junction in tubulo interstitial fibrosis rats induced by hyperuricemia and intervention effect of febuxostat on it

作　　者：陈敢[1] 周姗姗[1] 关昌杰[1] 刘日光[1] 秦曙光[1] CHEN Gan;ZHOU Shanshan;GUAN Changjie;LIU Riguang;Qin Shuguang(Department of Nephrology,Guangzhou First People‘s Hospital,Guangzhou 510180,China)

机构地区：[1]广州市第一人民医院肾内科,广州510180

出　　处：《广州医药》2021年第4期5-9,共5页Guangzhou Medical Journal

基　　金：广东省医学科研基金立项(A2018076)。

摘　　要：目的观察紧密连接蛋白在高尿酸血症致大鼠肾损害模型中的表达变化以及非布司他的干预疗效。方法将SD大鼠分为正常组,高尿酸血症组(模型组),非布司他组(干预组);氧嗪酸联合尿酸诱导制作高尿酸血症大鼠模型,给予非布司他进行干预,分别于6周后检测各组大鼠血中尿素氮(BUN)、血肌酐(Scr)、尿酸(UA)水平,免疫组化及RT-PCR方法检测紧密连接蛋白包括膜周蛋白-1(ZO-1)、跨膜蛋白(occludin)的表达变化,采用Masson染色检测大鼠肾间质病理改变。结果6周时,模型组、干预组ZO-1、occludin表达较正常组降低(均P<0.05);干预组ZO-1、occludin表达较模型组增加,差异有统计学意义(均P<0.05),与正常组相比,模型组、干预组RIF指数均增高(均P<0.05),干预组RIF指数低于模型组,高于正常组(均P<0.05)。结论紧密连接蛋白表达的降低在高尿酸血症肾间质纤维化发展过程中起着举足轻重的作用,并与血尿酸水平及肾功能损害密切相关。非布司他通过降低血尿酸水平,能改善紧密连接蛋白的表达,延缓肾功能损害,起到肾保护作用。Objective To observe the expression of tight junction protein in hyperuricemia induced renal damage model in rats and the intervention effect of febuxostat.Methods SD rats were randomly divided into three groups:normal control group,model control group,febuxostat treatment group.Hyperuricemia was induced in rats with oxonic acid per time for three times per day,by gavage and combined with uric acid added in drinking water,while febuxostat were administered by gavage in febuxostat treatment group.The blood of rats were collected to analyse the differences of control,model and treatment group on changes of blood urea nitrogen(BUN),creatinine(Cr),uric acid(UA).Immunohistochemistry was used to assay ZO-1 and occludin protein expression and quantitive real time PCR to detect the expression of ZO-1 and occludin in renal tissue of renal interstitial fibrosis model rats induced by hyperuricemia.Paraffin section of kidney was maked and then performed Masson staining to make sure the model is successful.Results At 6 weeks,the expressions of ZO-1 and occludin in the model group and treatment group were lower than those in the normal group(all P<0.05).The expressions of ZO-1 and occludin in the treatment group were higher than those in the model group(all P<0.05).Compared with the normal group,the RIF index in the model group and treatment group were higher(all P<0.05),and the RIF index in the treatment group was lower than that in the model group and higher than that in the normal group(all P<0.05).Conclusion The downregulated expression of ZO-1 and occludin plays a crucial role during the development of hyperuricemia in renal interstitial fibrosis,and are closely related to UA level and renal function impairment.Febuxostat may improve the expression of tight junction by downregurating UA,reduce renal fuction impairment and play a role in renal protection.

关 键 词：紧密连接蛋白 ZO-1 OCCLUDIN 高尿酸血症 非布司他 

分 类 号：R589.7[医药卫生—内分泌] R692.5[医药卫生—内科学]