The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary wall for preventing the leak of plasma proteins into primary urine.It is now accepted that the dysfunctio...The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary wall for preventing the leak of plasma proteins into primary urine.It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases.Nephrin,a gene product of NPHS1,a gene for a congenital nephrotic syndrome of Finnish type,constitutes an extracellular domain of the slit diaphragm.Podocin was identified as a gene product of NPHS2,a gene for a familial steroid-resistant nephrotic syndrome of French.Podocin binds the cytoplasmic domain of nephrin.After then,CD2 associated protein,NEPH1 and transient receptor potential-6 were also found as crucial molecules of the slit diaphragm.In order to explore other novel molecules contributing to the development of proteinuria,we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside nephropathy,a mimic of a human minimal change type nephrotic syndrome.Then we have found that synaptic vesicle protein 2B,ephrin-B1 and neurexin were already downregulated at the early stage of puromycin amino-nucleoside nephropathy,and that these molecules were localized close to nephrin.It is conceivable that these molecules are the slit diaphragm associated molecules,which participate in the regulation of the barrier function.These molecules could be targets to establish a novel therapy for nephrotic syndrome.展开更多
GENERAL INFORMATION World Journal of Nephrology(World J Nephrol,WJN,online ISSN2220-6124,DOI:10.5527)is a peer-reviewed open access(OA)academic journal that aims to guide clinical practice and improve diagnostic and t...GENERAL INFORMATION World Journal of Nephrology(World J Nephrol,WJN,online ISSN2220-6124,DOI:10.5527)is a peer-reviewed open access(OA)academic journal that aims to guide clinical practice and improve diagnostic and therapeutic skills of clinicians.Aim and scope WJN covers topics concerning kidney development,renal regeneration,kidney tumors,therapy of renal disease,hemodialysis,perito-展开更多
目的:探讨芪地固肾方治疗膜性肾病(MN)大鼠的效果及其可能的机制。方法:将40只SD雄性大鼠随机分为模型组(等剂量生理盐水尾静脉注射)、雷公藤多甙片组(10 mg/kg雷公藤多甙片)、芪地固肾方低剂量组(15.425 g/kg芪地固肾方)、芪地固肾方...目的:探讨芪地固肾方治疗膜性肾病(MN)大鼠的效果及其可能的机制。方法:将40只SD雄性大鼠随机分为模型组(等剂量生理盐水尾静脉注射)、雷公藤多甙片组(10 mg/kg雷公藤多甙片)、芪地固肾方低剂量组(15.425 g/kg芪地固肾方)、芪地固肾方高剂量组(61.7 g/kg芪地固肾方)四组,另取10只未造模大鼠作为空白组(等剂量生理盐水尾静脉注射),连续干预28天后,检测24小时尿蛋白定量(U-TP)、血清总蛋白(TP)、白蛋白(ALB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(Scr)、尿素氮(BUN)的变化;HE染色、透射电镜观察大鼠肾组织病理学改变;RT-PCR检测肾组织中nephrin蛋白、podocin m RNA的表达。结果:与空白组比较,模型组24 hU-TP、足细胞nephrin和podocin m RNA显著升高,血清TP和ALB显著降低(P<0.01);与模型组比较,各给药组24 hU-TP降低,血清TP和ALB显著升高(P<0.05);肾组织免疫复合物沉积减少,肾小球基底膜增厚减轻;足细胞nephrin和podocin m RNA表达升高(P<0.05)。结论:芪地固肾方能够降低MN模型大鼠的尿蛋白水平,减轻肾脏病理损伤,上调肾组织中足细胞裂孔隔膜蛋白nephrin和podocin m RNA的表达,延缓膜性肾病的进展。展开更多
文摘The slit diaphragm bridging the neighboring foot processes functions as a final barrier of glomerular capillary wall for preventing the leak of plasma proteins into primary urine.It is now accepted that the dysfunction of the sit diaphragm contributes to the development of proteinuria in several glomerular diseases.Nephrin,a gene product of NPHS1,a gene for a congenital nephrotic syndrome of Finnish type,constitutes an extracellular domain of the slit diaphragm.Podocin was identified as a gene product of NPHS2,a gene for a familial steroid-resistant nephrotic syndrome of French.Podocin binds the cytoplasmic domain of nephrin.After then,CD2 associated protein,NEPH1 and transient receptor potential-6 were also found as crucial molecules of the slit diaphragm.In order to explore other novel molecules contributing to the development of proteinuria,we performed a subtraction hybridization assay with a normal rat glomerular RNA and a glomerular RNA of rats with a puromycin aminonucleoside nephropathy,a mimic of a human minimal change type nephrotic syndrome.Then we have found that synaptic vesicle protein 2B,ephrin-B1 and neurexin were already downregulated at the early stage of puromycin amino-nucleoside nephropathy,and that these molecules were localized close to nephrin.It is conceivable that these molecules are the slit diaphragm associated molecules,which participate in the regulation of the barrier function.These molecules could be targets to establish a novel therapy for nephrotic syndrome.
文摘GENERAL INFORMATION World Journal of Nephrology(World J Nephrol,WJN,online ISSN2220-6124,DOI:10.5527)is a peer-reviewed open access(OA)academic journal that aims to guide clinical practice and improve diagnostic and therapeutic skills of clinicians.Aim and scope WJN covers topics concerning kidney development,renal regeneration,kidney tumors,therapy of renal disease,hemodialysis,perito-
文摘目的:探讨芪地固肾方治疗膜性肾病(MN)大鼠的效果及其可能的机制。方法:将40只SD雄性大鼠随机分为模型组(等剂量生理盐水尾静脉注射)、雷公藤多甙片组(10 mg/kg雷公藤多甙片)、芪地固肾方低剂量组(15.425 g/kg芪地固肾方)、芪地固肾方高剂量组(61.7 g/kg芪地固肾方)四组,另取10只未造模大鼠作为空白组(等剂量生理盐水尾静脉注射),连续干预28天后,检测24小时尿蛋白定量(U-TP)、血清总蛋白(TP)、白蛋白(ALB)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、血肌酐(Scr)、尿素氮(BUN)的变化;HE染色、透射电镜观察大鼠肾组织病理学改变;RT-PCR检测肾组织中nephrin蛋白、podocin m RNA的表达。结果:与空白组比较,模型组24 hU-TP、足细胞nephrin和podocin m RNA显著升高,血清TP和ALB显著降低(P<0.01);与模型组比较,各给药组24 hU-TP降低,血清TP和ALB显著升高(P<0.05);肾组织免疫复合物沉积减少,肾小球基底膜增厚减轻;足细胞nephrin和podocin m RNA表达升高(P<0.05)。结论:芪地固肾方能够降低MN模型大鼠的尿蛋白水平,减轻肾脏病理损伤,上调肾组织中足细胞裂孔隔膜蛋白nephrin和podocin m RNA的表达,延缓膜性肾病的进展。
