特异性NF-κB抑制剂对单侧输尿管梗阻大鼠肾间质纤维化的治疗作用

Effect of the specific inhibitor of NF-κB on renal interstitial fibrosis in unilateral ureteral obstruction rat models

目的探讨特异性NF-κB抑制剂对单侧输尿管梗阻大鼠肾间质纤维化的治疗作用及其可能机制。方法应用特异性NF-κB抑制剂PDTC治疗单侧输尿管梗阻大鼠模型,常规HE、PASM染色观察肾间质病理变化,电泳迁移率变动分析法检测肾组织中NF-κB的活性,免疫组化法检测TGF-β1、MCP-1的表达,并采用图像分析系统进行半定量分析。结果治疗组较模型组大鼠梗阻侧肾脏病理变化明显减轻,肾皮质NF-κB活性及小管间质TGF-β1、MCP-1表达明显降低(P<0·01)。结论特异性NF-κB抑制剂通过抑制NF-κB激活并进一步减少下游炎症和致纤维化细胞因子的表达以达到治疗肾间质纤维化的作用。

Aim To study the therapeutic effects of specific inhibitor of nuclear factor-kB on renal interstitial fibrosis and its possible mechanism in unilateral ureteral obstruction. Methods Rats were received unilateral ureteral obstruction operation, and then administered with PDTC, a putative specific inhibitor of NF- kB. Then the pathologic injuries of the kidneys in each group were evaluated. The renal NF-kB-DNA binding activity was detected by electrophoretic mobility shift assay（EMSA） and semi-quantitative analysis. The renal expression of TGF-β1, MCP-1 was examined respectively by immunohistochemistry and semi-quantitative analysis. Results In therapy group,the renal mor-phologic changes attenuated significantly, the NF-kB- DNA binding activity was inhibited evidently, the expression of TGF-β1 ,MCP-1 decreased remarkably（ P 〈 0. 01 ） compared with those in control group. Conclusion Specific inhibitor of NF-kB could inhibit renal interstitial fibrosis through inhibiting the activity of NF- kB and then influencing some downstream inflammatory and fibrogenesis cytokines subsequently.