To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2(Adanti-ERK2)gene therapy upon chronic allograft nephropathy(CAN)of rats,male Lewis(LEW,RT11)rats received male Fisher(F344,RT11v...To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2(Adanti-ERK2)gene therapy upon chronic allograft nephropathy(CAN)of rats,male Lewis(LEW,RT11)rats received male Fisher(F344,RT11v1)renal allografts.The recipients were divided into three groups:(1)empty control group;(2)vector control group;(3)gene therapy group.All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation.Morphometric analysis was used to determine thefibrosis of grafts.Immunohistochemistry was used to detect the expression of E-Cadherin,Vimentin,TβR I and the infiltration of CD4+T lymphocyte,CD8+T lymphocyte and ED-1+monocytes.Enzyme linked immunosorbent assay(ELISA)was used to detect TGF-β1 in serum.The grafts in the empty control group and vector control group showed CAN.There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I.In the gene therapy group,thefibrosis was ameliorated and fewer T lymphocytes and ED-1+monocytes infiltrated in the interstitium.There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats.Compared with the empty control group,the expression of TGF-β1 in the gene therapy group was down-regulated.Adanti-ERK2 gene therapy protects the renal allograft and attenuates graftfibrosis,which may be correlated with a decreased renal tubular epithelial mesenchymal transition,a decreased infiltration of CD4+T lymphocyte,CD8+T lymphocytes and ED-1+monocytes in renal interstitium,and the down-regulated TGF-β1 expression.展开更多
目的探讨慢性移植物肾病中补体C4d的沉积及其意义。方法选择慢性移植物肾病活检标本(C A N组,n=28),应用免疫组化和间接免疫荧光法检测C4d在移植肾组织中的沉积,比较其与正常移植肾组织(对照组,n=10)间的差异。结果对照组肾小管周毛细...目的探讨慢性移植物肾病中补体C4d的沉积及其意义。方法选择慢性移植物肾病活检标本(C A N组,n=28),应用免疫组化和间接免疫荧光法检测C4d在移植肾组织中的沉积,比较其与正常移植肾组织(对照组,n=10)间的差异。结果对照组肾小管周毛细血管无C4d的沉积,但肾小球系膜区、基底膜和肾小管基膜上有C4d的弥漫沉积,部分动脉内膜也有C4d的沉积。C AN组8例(29%)出现管周毛细血管内皮细胞C4d的线性沉积,而肾小球毛细血管少见C4d的沉积(1/28,4%)。间接免疫荧光法显示C4d弥漫性沉积,主要见于管周毛细血管内皮细胞。结论补体的活化导致裂解片断的沉积,慢性移植物肾病中出现肾组织C4d的沉积,体液免疫可能是导致慢性移植肾损伤的一个原因。展开更多
目的研究联合应用血管紧张素转换酶抑制剂依那普利和冬虫夏草发酵制剂百令胶囊对慢性移植肾肾病(CAN)患者肾功能的影响。方法以CAN患者84例为研究对象,随机分为4组:依那普利及百令胶囊联合治疗组(联合治疗组,22例),依那普利组(20例),百...目的研究联合应用血管紧张素转换酶抑制剂依那普利和冬虫夏草发酵制剂百令胶囊对慢性移植肾肾病(CAN)患者肾功能的影响。方法以CAN患者84例为研究对象,随机分为4组:依那普利及百令胶囊联合治疗组(联合治疗组,22例),依那普利组(20例),百令胶囊组(21例)和对照组(21例)。4组均给予常规免疫抑制治疗,在此基础上联合治疗组、依那普利组、百令胶囊组分别加用相应药物。于治疗前、治疗第6、9个月时分别检测各组患者的SCr、BUN、CCr、24 h尿总蛋白(24 h Upro)和尿转化生长因子-β1(TGF-β1)浓度。结果治疗6个月后联合治疗组的CCr明显升高,SCr降低,24 h Upro减少,尿TGF-β1浓度降低,且均明显低于对照组,联合治疗、依那普利、百令胶囊组的指标差异无统计学意义(P>0.05)。治疗9个月后联合治疗、依那普利、百令胶囊组的SCr进一步降低(P<0.01),CCr有所升高,而对照组CCr显著下降(P<0.05)。联合治疗组肾功能好转和稳定病例数高于依那普利组。结论联合应用依那普利和百令胶囊治疗CAN,可以更好地减少患者尿蛋白的排出,改善移植肾功能,延缓CAN发展进程,其临床疗效优于依那普利或百令胶囊单一使用。展开更多
基金supported by the National Natural Science Foundation of China(Grant No.30300324).
文摘To investigate the effect and underlying mechanism of adenovirus-mediated antisense ERK2(Adanti-ERK2)gene therapy upon chronic allograft nephropathy(CAN)of rats,male Lewis(LEW,RT11)rats received male Fisher(F344,RT11v1)renal allografts.The recipients were divided into three groups:(1)empty control group;(2)vector control group;(3)gene therapy group.All recipients were sacrificed for the grafts and serum analysis at the 24th week after transplantation.Morphometric analysis was used to determine thefibrosis of grafts.Immunohistochemistry was used to detect the expression of E-Cadherin,Vimentin,TβR I and the infiltration of CD4+T lymphocyte,CD8+T lymphocyte and ED-1+monocytes.Enzyme linked immunosorbent assay(ELISA)was used to detect TGF-β1 in serum.The grafts in the empty control group and vector control group showed CAN.There was less E-Cadherin in renal tubular epithelial cells in the empty control group but more Vimentin and TβR I.In the gene therapy group,thefibrosis was ameliorated and fewer T lymphocytes and ED-1+monocytes infiltrated in the interstitium.There was no significant difference in the expression of E-Cadherin between the gene therapy group and normal rats.Compared with the empty control group,the expression of TGF-β1 in the gene therapy group was down-regulated.Adanti-ERK2 gene therapy protects the renal allograft and attenuates graftfibrosis,which may be correlated with a decreased renal tubular epithelial mesenchymal transition,a decreased infiltration of CD4+T lymphocyte,CD8+T lymphocytes and ED-1+monocytes in renal interstitium,and the down-regulated TGF-β1 expression.
文摘目的探讨慢性移植物肾病中补体C4d的沉积及其意义。方法选择慢性移植物肾病活检标本(C A N组,n=28),应用免疫组化和间接免疫荧光法检测C4d在移植肾组织中的沉积,比较其与正常移植肾组织(对照组,n=10)间的差异。结果对照组肾小管周毛细血管无C4d的沉积,但肾小球系膜区、基底膜和肾小管基膜上有C4d的弥漫沉积,部分动脉内膜也有C4d的沉积。C AN组8例(29%)出现管周毛细血管内皮细胞C4d的线性沉积,而肾小球毛细血管少见C4d的沉积(1/28,4%)。间接免疫荧光法显示C4d弥漫性沉积,主要见于管周毛细血管内皮细胞。结论补体的活化导致裂解片断的沉积,慢性移植物肾病中出现肾组织C4d的沉积,体液免疫可能是导致慢性移植肾损伤的一个原因。
文摘目的研究联合应用血管紧张素转换酶抑制剂依那普利和冬虫夏草发酵制剂百令胶囊对慢性移植肾肾病(CAN)患者肾功能的影响。方法以CAN患者84例为研究对象,随机分为4组:依那普利及百令胶囊联合治疗组(联合治疗组,22例),依那普利组(20例),百令胶囊组(21例)和对照组(21例)。4组均给予常规免疫抑制治疗,在此基础上联合治疗组、依那普利组、百令胶囊组分别加用相应药物。于治疗前、治疗第6、9个月时分别检测各组患者的SCr、BUN、CCr、24 h尿总蛋白(24 h Upro)和尿转化生长因子-β1(TGF-β1)浓度。结果治疗6个月后联合治疗组的CCr明显升高,SCr降低,24 h Upro减少,尿TGF-β1浓度降低,且均明显低于对照组,联合治疗、依那普利、百令胶囊组的指标差异无统计学意义(P>0.05)。治疗9个月后联合治疗、依那普利、百令胶囊组的SCr进一步降低(P<0.01),CCr有所升高,而对照组CCr显著下降(P<0.05)。联合治疗组肾功能好转和稳定病例数高于依那普利组。结论联合应用依那普利和百令胶囊治疗CAN,可以更好地减少患者尿蛋白的排出,改善移植肾功能,延缓CAN发展进程,其临床疗效优于依那普利或百令胶囊单一使用。