矢志方减轻高尿酸血症大鼠肾小管损伤的作用机制研究  

Study on protective effect and mechanism of Shizhifang Formula on renal tubular injury in hyperuricemia rats

作　　者：李瑞玲[1,2] 吴燕升[1] 李东东 史丽强 高建东[1] LI Ruiling;WU Yansheng;LI Dongdong;SHI Liqiang;GAO Jiandong(Department of Nephrology,Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,TCM Institute of Kidney Disease,Shanghai University of Traditional Chinese Medicine,Key Laboratory of Liver and Kidney Diseases,Shanghai University of Traditional Chinese Medicine,Ministry of Education,Shanghai Key Laboratory of Traditional Chinese Clinical Medicine,Shanghai 201203,China;Outpatient Department,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属曙光医院肾病科,上海中医药大学中医肾病研究所,上海中医药大学肝肾疾病病证教育部重点实验室,上海市中医临床重点实验室,上海201203 [2]上海中医药大学门诊部,上海201203

出　　处：《上海中医药杂志》2021年第7期85-90,共6页Shanghai Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81373613,81874437,81904126)。

摘　　要：目的探索矢志方减轻高尿酸血症大鼠肾小管损伤的作用机制。方法32只大鼠按体质量随机分为正常组、模型组、矢志方组、别嘌醇组,每组8只;以750 mg/kg氧嗪酸钾造模,各组分别于实验的第3、5、7、11周末留取10只大鼠24 h尿液,检测24 h尿蛋白定量、尿β-N-乙酰氨基葡萄糖苷酶(NAG)、尿视黄醇结合蛋白(RBP)水平;免疫组化法、Real-time PCR、Western blot检测Ⅲ型胶原(CollagenⅢ)和骨桥蛋白(OPN)的表达。结果第11周末,模型组NAG水平显著高于正常组(P<0.05),RBP水平较正常组在第5、7、11周末均有不同程度升高(P<0.05),用药后可降低尿中RBP排泄。矢志方组、别嘌醇组collagenⅢ、OPN mRNA的表达自3周起较模型组升高(P<0.01,P<0.05),两组各时间节点OPN mRNA的表达无差异(P>0.05)。与模型组比较,各时间段各组大鼠肾组织中collagenⅢ表达明显降低(P<0.05);除第3周外,各组大鼠肾组织中OPN表达明显降低(P<0.01)。第3周末,矢志方组、别嘌醇组之间collagenⅢ表达无差异(P>0.05);第3、7周末两组之间OPN表达无差异(P>0.05)。免疫组化可见模型组collagenⅢ和OPN表达于肾小管及间质,肾小球在模型后期有少量表达。结论高尿酸血症大鼠肾小管微量蛋白排泄增多,高尿酸血症存在明显的肾小管和间质损伤,矢志方具有减轻肾小管损伤、抑制肾脏间质炎症、缓解肾纤维化的作用。Objective To explore the protective effect and mechanism of Shizhifang Formula on renal tubular injury in hyperuricemia rats.Methods Thirty two rats were randomly divided into 4 groups according to their body weight:normal group,model group,Shizhifang Formula group and allopurinol group,8 rats in each group.The rats were given 750 mg/kg OA suspension to establish hyperuricemic model.At the end of the 3rd,5th,7th and 11th week of the experiment,24-hour urine was taken in each group with 10 rats,and 24-hour urine protein quantification,renal tubular function index NAG and RBP were further detected.Immunohistochemistry,real time PCR and Western blot were used to detect the expression of collagenⅢand osteopantin(OPN).Results At the end of the 11th week,NAG in the model group was significantly higher than that in the normal group(P<0.05).RBP in hyperuricemic rats was higher than that in normal rats in 5 weeks,7 weeks and 11 weeks(P<0.05).Compared with the allopurinol group,the expression of collagenⅢand OPN mRNA in Shizhifang Formula group and allopurinol group increased significantly(P<0.01,P<0.05)from three weeks,and there was no difference in the expression of OPN mRNA between the two groups at each time node(P>0.05).Compared with the model group,the expression of collagenⅢin renal tissue of rats in the normal group was decreased significantly(P<0.05).Except for 3 weeks,the expression of OPN in renal tissue of rats in each group decreased significantly(P<0.01).There was no difference in the expression of collagenⅢbetween the two treatment groups at the end of the 3th week(P>0.05),and there was no difference in the expression of OPN between the two treatment groups at the end of the 3th week and the 7 the week(P>0.05).The expression of collagenⅢand OPN in renal tubules and interstitium in the model group was observed by immunohistochemistry,and there was a little expression in glomerulus in the later stage of the model.Conclusions In this study,the excretion of urinary microproteins in hyperuricemia rats w

关 键 词：矢志方 高尿酸血症 肾小管损伤 模型大鼠 中药研究 

分 类 号：R285[医药卫生—中药学]