阿霉素肾病大鼠肾组织乙酰肝素酶表达改变及其对蛋白尿的影响

目的观察阿霉素肾病大鼠肾组织乙酰肝素酶(HPA)、硫酸乙酰肝素蛋白多糖(HSPG)、碱性成纤维细胞生长因子(bFGF)、血小板源性生长因子(PDGF)的表达变化。方法清洁级健康雄性SD大鼠随机分为对照组(NC组)和阿霉素肾病组(AN组),分别观察0、7、14、21、28天的24h尿蛋白定量,0、14、21、28天血清白蛋白、尿素、肌酐、甘油三酯和胆固醇水平以及肾小球HPA、HSPG、bFGF、PDGF表达的改变。结果 AN组造模后14、21及28天24h尿蛋白定量较同时间点NC组及同组前一时间点明显升高,差异有统计学意义(P<0.05);同时AN组在造模后各观察时间点HPA与PDGF表达显著增多,且随观察时间延长增加,与NC组相比差异有统计学意义(P<0.05);AN组在造模后各观察时间点HSPG表达较NC组显著减少,且随观察时间延长降低,差异有统计学意义(P<0.05);bFGF在NC组及AN组各观察时间点表达均未见明显变化(P>0.05);HPA表达与HSPG表达呈负相关(r=-0.757,P<0.05),与PDGF表达及蛋白尿呈正相关(r=0.899,P<0.05;r=0.868,P<0.05)。结论 HPA表达增加导致HSPG水解增多,同时释放出PDGF等因子,肾小球基膜的物理屏障和电荷屏障受损,促进蛋白尿的发生发展。

Expression Changes of Heparanase and Its Effects on Proteinuria in Adriamycin-induced Nephropathy Rats

Objective To observe the expression change of heparanase(HPA),heparan sulfate proteoglycan(HSPG),basic fibroblast growth factor(bFGF) and platelet-derived growth factor(PDGF) in rats with adriamycin-induced nephropathy.Methods Forty rats were randomly divided into two groups:the normal control group(NC) and the adriamycin nephropathy group(AN),and the latter was induced by intravenous injection of adriamycin.The 24h urine samples were collected at 0,7,14,21,28 days,and serum and renal tissue samples were collected at 0,14,21,28 days respectively to observe the changes of 24h proteinuria,serum albumin,urea,creatinine,triglyceride,cholesterol and expressions of HPA,HSPG,bFGF,PDGF.Results The 24h proteinuria quantities in AN at 14,21 and 28 days were significant higher than those of NC(P<0.05).Compared to NC,the expressions of HPA and PDGF in AN were increased significantly along with the time prolonged(P<0.05),but the expressions of HSPG were decreased(P<0.05).The expressions of bFGF in two groups were not changed(P>0.05).The expressions of HPA were positively correlated with proteinuria and expression of PDGF,but negatively correlated with HSPG.Conclusion The increased expression of HPA leads to dissociation of HSPG and releasing PDGF,which injuried the physical and electrostatic barrier of glomerular basement membrane and promoting the proteinuria.