中文摘要：

目的研究腺病毒介导的反义ERK2（Adanti-ERK2）基因转染供肾对减缓肾移植后发生慢性移植肾肾病（CAN）的作用及机制。方法建立大鼠间肾移植模型。按供肾移植前处理方式的不同分为对照组、空载病毒组和基因转染组，每组6只。对照组供肾灌注无菌HTK液0．5ml，空载病毒组供肾灌注含5×10^9pfuLacZ基因腺病毒（Ad-LacZ）的HTK液0．5ml，基因转染组供肾灌注含5×10^9pfuAdantbERK2的HTK液0．5m1。肾移植术后24周行移植肾的病理学观察，免疫组织化学法观察肾小管上皮细胞表面标志蛋白E-Cadherin、Vimentin、TβRⅠ的表达以及CD4＋、CD8＋T淋巴细胞和ED-1＋细胞的浸润情况；酶联免疫法检测受者血清中转化生长因子β（TGF-β1）的含量。结果肾移植术后24周，对照组和空载病毒组移植肾呈CAN表现；肾小球硬化，肾小管萎缩明显，伴严重间质纤维化以及明显的CD4＋、CD8＋T淋巴细胞和ED-1＋细胞浸润；病变区肾小管上皮细胞E-Cadherin表达减少，Vimentin、TβRI表达显著增多。基因转染组移植肾间质内仅有少量CD4＋、CD8＋T淋巴细胞和ED-1＋细胞浸润；肾小管上皮细胞E-Cadherin表达正常。对照组和空载病毒组血清中TGF-β。含量明显高于基因转染组。结论AdantkERK2基因转染移植肾可减缓CAN的发生，对移植肾具有保护作用。这种保护机制可能与减少炎症细胞的浸润、下调TGF-β等致纤维化因子的表达以及抑制肾小管上皮细胞向间充质细胞的转化有关。

英文摘要：

Objective To investigate the effect and underlying mechanism of adenovirusmediated antisense ERK2 （Adanti-ERK2） gene therapy upon chronic allograft nephropathy （CAN） of rats. Methods Male Lewis （LEW, RT11 ） rat received male Fisher （F344, RT11v1 ） renal allograft. The recipients were divided into 3 groups： （1） control group; （2） vector control group; （3） gene therapy group. The pathological observation of the transplanted kidneys was done at 24th week after renal transplantation. Morphometric analysis was used to determine the fibrosis 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. ELISA was used to test the levels of TGF-β1 in serum. Results The renal grafts in control group and vector control group showed the features of CAN. There were less E-Cadherin in renal tubular epithelial cells in control group but more Vimentin and TβR I . In gene therapy group, the fibrosis was ameliorated and less T lymphocytes and ED-1＋ monocytes infiltrated in the interstitium. The expression of E-Cadherin showed no significant difference between gene therapy group and normal control group. As compared with the control groups, the expression of TGF-β1 in gene therapy group was down-regulated. Conclusions Adanti-ERK2 gene therapy protects renal allografts and attenuates graft fibrosis, which may be correlated with the decreased renal tubular epithelial mesenchymal transition , the decreased infiltration of CD4＋ T lymphocyte, CD8＋ T lymphocytes and ED-1＋ monocytes in renal interstitium, and the down-regulated TGF-β1 expression.