乙酰肝素酶在糖尿病肾病大鼠蛋白尿发生中的作用

Role of heparanase in the pathogenesis of proteinuria in diabetic nephropathy rats

目的观察糖尿病肾病大鼠肾组织乙酰肝素酶（HPA）的表达，探讨其在糖尿病肾病大鼠蛋白尿发生中的作用。方法SD健康大鼠被随机分为健康对照组（n=6）、糖尿病6周组（DM6w，n=10）和糖尿病12周组（DM12w，n=10），采用一次性腹腔注射链脲菌素（STZ）的方法建立糖尿病大鼠模型。分别于造模后6周和12周末测定各组大鼠相对肾质量、血糖、尿素氮、血肌酐、24h尿量及尿蛋白量（24h）等指标，并观察肾脏病理改变。RT．PCR和免疫组织化学法检测各组大鼠肾组织HPAmRNA和蛋白表达变化，并分析其与蛋白尿发生的相关性。结果（1）DM6w和DM12W组大鼠的相对肾质量、血糖、尿素氮、24h尿量及尿蛋白量（24h）与健康对照组相比明显升高，差异均有统计学意义（P〈0．05或P〈0.01）。（2）DM6w和DM12w组大鼠HPAmRNA和蛋白表达比健康对照组均显著增高（P〈0．01）。（3）大鼠肾组织HPAmRNA和蛋白表达与尿蛋白量（24h）之间均呈正相关（r=0．783，P〈0．01；r=0．793，P〈0．01）。结论HPA在糖尿病肾病中的表达升高可能参与了糖尿病肾病蛋白尿的发生。

Objective To observe the expression of heparanase （HPA） in kidney of diabetic nephropathy （DN） rats and to investigate the role of HPA in the pathogenesis of proteinuria in DN rats. Methods DM rat models induced by intraperitoneal injection with streptozotocin were constructed. Twenty-six rats were randomly divided into healthy control group （n=6）, DM 6-week group（n=10） and DM 12-week group（n=10）. Relative kidney weight（ RKW ）, blood glucose, BUN, Scr, 24-hour urine volume and 24-hour proteinuria quantitation were measured, and renal morphology was observed after 6 and 12 weeks. The expression of HPA was examined by immunohistochemistry and reverse transcription PCR. Results （1） Compared with the control group, RKW, blood glucose, BUN, 24-hour urine volume and 24-hour proteinuria quantitation of DM groups increased markedly （P〈 0.05 or P〈0.01）. （2） Compared to the control group, the expression of HPA mRNA and protein in DM groups increased significantly （P〈0.01）. （3） HPA protein and mRNA were positively correlated with the quantification of urinary protein （r=0.783, P〈 0.01; r=0.793, P〈0.01）. Conclusion The increased expression of HPA maybe participate in the pathogenesis of proteinuria in DN.