方格星虫提取物对膜性肾病模型的治疗作用及机制初探

目的:初步探讨方格星虫粗提物(SNP)对膜性肾病(MN)的治疗作用及其可能机制。方法:50只SD大鼠随机分为模型组和对照组,模型组大鼠腹腔一次注入抗FxlA血清建立被动性Heymann肾炎模型,模型建立1周后依24 h尿蛋白排泄量(24 h UPE)随机将Heymann肾炎大鼠分为SNP治疗组和未治疗组,治疗组用SNP灌胃治疗。考马斯亮蓝法每周测定24 h UPE。治疗4周结束后处死大鼠取双肾,光镜、电镜观察肾脏病理改变,RT-PCR法检测肾组织nephrin mRNA和podocin mRNA的表达量。结果:SNP治疗4周后大鼠24 h UPE较未治疗组降低(P<0.05);模型组大鼠肾小球基底膜增厚,上皮下电子致密物沉积,足细胞足突融合等病理改变,SNP治疗组大鼠上述病变较未治疗组减轻,经测定,足细胞足突融合率较未治疗组显著降低(P<0.01);SNP治疗组nephrin mRNA和podocin mRNA表达量较未治疗组升高(P<0.05)。结论:SNP可通过上调膜性肾病大鼠足细胞nephrin和podocin基因表达水平,一定程度上减轻足细胞足突融合,进而减少尿蛋白滤过,可能对人类膜性肾病具有辅助治疗作用。

Effects and Mechanism of Sipunculus Nudus Preparation on Model of Membranous Nephropathy

Objective:To explore whether Sipunculus nudus preparation(SNP) has a therapeutic effect against membrane nephropathy(MN) in rat model and to investigate the possible mechanism.Methods:Rat passive Heymann nephritis models were duplicated by injection of anti-FxlA sera for one week.Then the rats with passive Heymann nephritis were randomly divided into SNP-treated group,which received SNP for 4 weeks,and untreated group.24 h urinary protein excretion(24 h UPE) was measured weekly.Renal pathological and ultrastructure change was evaluated,and expression of nephrin and podocin mRNA in renal tissue was also assessed.Results:24 h UPE was decreased significantly in SNP-treated group compared to untreated group(P<0.05).Typical pathological features including thickened GBM,subepithelial electron dense deposits,podocyte foot process fusion were found in untreated group,while all the injury was alleviated in SNP-treated group.The ratio of foot process fusion in SNP-treated group was much lower than that in untreated group(P<0.01).Expression of nephrin and podocin mRNA was increased in SNP-treated group compared to untreated group(P<0.05).Conclusion:SNP may up-regulate the expression of nephrin and podocin,attenuate the podocyte injury and decrease urinary protein filtration in rat MN models.These findings have important implications for SNP in the treatment of human MN.