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
目的观察雷公藤多甙(multi-glycoside of Tripterygium wilfordii Hook.f.,GTW)对抗Thy1.1抗体肾炎蛋白尿和足细胞裂隙膜相关分子(nephrin、podocin)表达的影响。方法经尾静脉一次性注射500μg单克隆抗体(monoclonal antibody,mAb)1-22-...目的观察雷公藤多甙(multi-glycoside of Tripterygium wilfordii Hook.f.,GTW)对抗Thy1.1抗体肾炎蛋白尿和足细胞裂隙膜相关分子(nephrin、podocin)表达的影响。方法经尾静脉一次性注射500μg单克隆抗体(monoclonal antibody,mAb)1-22-3建立大鼠抗Thy1.1抗体肾炎模型。14只大鼠随机分为GTW干预组(简称GTW组)和安慰剂干预组(简称造模组)。实验1中,在注射抗体前3天,经灌胃给予GTW〔75mg/(kg.d)〕或安慰剂,直至造模后第14天,处死大鼠;实验2中,在注射抗体同时,经灌胃给予GTW〔100mg/(kg.d)〕或安慰剂,直至造模后第7天,处死大鼠。分别观察14天内或7天内模型鼠24h尿蛋白排泄量(urinary protein excretion,Upro)动态变化。在第14天或第7天,处死大鼠后,取出肾脏,分别观察肾小球形态学变化、肾小球内巨噬细胞浸润、肾小球内nephrin、podocin及其核酸表达。结果实验1中,GTW抑制抗Thy1.1抗体肾炎蛋白尿和系膜损伤,在第14天,对肾小球内nephrin、podocin免疫荧光染色强度无影响;实验2中,GTW改善抗Thy1.1抗体肾炎蛋白尿、系膜损伤、肾小球内巨噬细胞浸润,而且,在第7天,显著增强肾小球内nephrin、podocin及其核酸表达。结论在抗Thy1.1抗体肾炎中,nephrin、podocin表达的减弱可能会促进系膜损伤和蛋白尿。GTW改善系膜损伤和蛋白尿的作用,很可能是通过增强nephrin、podocin表达来实现的。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.
文摘目的观察雷公藤多甙(multi-glycoside of Tripterygium wilfordii Hook.f.,GTW)对抗Thy1.1抗体肾炎蛋白尿和足细胞裂隙膜相关分子(nephrin、podocin)表达的影响。方法经尾静脉一次性注射500μg单克隆抗体(monoclonal antibody,mAb)1-22-3建立大鼠抗Thy1.1抗体肾炎模型。14只大鼠随机分为GTW干预组(简称GTW组)和安慰剂干预组(简称造模组)。实验1中,在注射抗体前3天,经灌胃给予GTW〔75mg/(kg.d)〕或安慰剂,直至造模后第14天,处死大鼠;实验2中,在注射抗体同时,经灌胃给予GTW〔100mg/(kg.d)〕或安慰剂,直至造模后第7天,处死大鼠。分别观察14天内或7天内模型鼠24h尿蛋白排泄量(urinary protein excretion,Upro)动态变化。在第14天或第7天,处死大鼠后,取出肾脏,分别观察肾小球形态学变化、肾小球内巨噬细胞浸润、肾小球内nephrin、podocin及其核酸表达。结果实验1中,GTW抑制抗Thy1.1抗体肾炎蛋白尿和系膜损伤,在第14天,对肾小球内nephrin、podocin免疫荧光染色强度无影响;实验2中,GTW改善抗Thy1.1抗体肾炎蛋白尿、系膜损伤、肾小球内巨噬细胞浸润,而且,在第7天,显著增强肾小球内nephrin、podocin及其核酸表达。结论在抗Thy1.1抗体肾炎中,nephrin、podocin表达的减弱可能会促进系膜损伤和蛋白尿。GTW改善系膜损伤和蛋白尿的作用,很可能是通过增强nephrin、podocin表达来实现的。
