狼疮性肾炎肾组织中NF-κB p65的表达及与细胞增殖的关系  

Change of NF-κB p65 expression in renal tissue of lupus nephritis and correlation with cell proliferation

作　　者：康朋朋 张玉军[1] 张景坤[1] 王冀[2] 刘青娟[1] 陈宁[1] 吴海江[1] 刘淑霞[1] 

机构地区：[1]河北医科大学病理学教研室,石家庄050017 [2]河北医科大学教务处,石家庄050017

出　　处：《临床与实验病理学杂志》2013年第12期1332-1336,共5页Chinese Journal of Clinical and Experimental Pathology

基　　金：国家自然科学基金(81000301);河北省自然科学基金(C2010000463);教育部博士点基金(20101323120007);河北省教育厅自然科学研究计划(Z2009151)

摘　　要：目的探讨核因子κB(nuclear factor-kappa B,NF-κB)p65在狼疮性肾炎肾组织中的表达变化及与细胞增殖的关系。方法采用原位杂交技术检测狼疮性肾炎活检肾组织中NF-κB p65 mRNA和蛋白的表达;采用RT-PCR、Western blot和免疫组化SABC法检测狼疮鼠(BXSB鼠)和C57BL/6鼠肾组织中NF-κB p65 mRNA和蛋白的表达及其核转位;将常规培养的小鼠系膜细胞随机分为正常对照组、高迁移率族蛋白1(high mobility group protein box 1,HMGB1)刺激组和HMGB1+PDTC组,Western blot法检测NF-κB p65表达,免疫细胞化学检测PCNA蛋白表达。结果 (1)狼疮性肾炎活检肾组织中NF-κB mRNA及蛋白表达升高,且定位于细胞核;(2)BXSB鼠肾组织中NF-κB p65 mRNA和蛋白表达均升高,肾小球内NF-κB p65核表达明显增强;(3)重组HMGB1可促进体外培养的小鼠系膜细胞NF-κB磷酸化;(4)PDTC可降低HMGB1诱导的系膜细胞增殖。结论狼疮性肾炎发病过程中伴NF-κB信号途径的激活,且可参与系膜细胞的增殖。Purpose To explore the change of NF-κB p65 expression in renal tissue of lupus nephritis and correlation with cell prolif-eration. Methods In situ hybridization and immunohistochemistry were used to detect the NF-κB p65 mRNA and protein expression in the renal tissue of lupus nephritis （LN） patients. NF-κBB p65 mRNA and protein expression in renal tissue of BXSB mice were de-tected by RT-PCR, Western blot and immunohistochemistry. Mouse mesangial cell （MMC） selected for the study were randomly divid-ed into control group, HMGB1 stimulation group and HMGB1 ＋ PDTC group. The cells were collected at 50 min and 8 h. Western blot was used to detect the expression of NF-κB p65 protein. Immunocytoehemistry was used to detect the expression of PCNA. Results （ 1 ） The expression of NF-κB p65 mRNA and protein in renal tissue of LN patients increased and the protein mainly located in nuclei especially in glomeruli. （2） Compared with C57BL/6 mice, the NF-κB p65 mRNA and protein in renal tissue of BXSB mice signifi-cantly increased and positive expression of p65 protein located in the nuclei of glomeruli. （3） HMGB1 promoted NF-κB phosphoryla-tion and nuclear translocation in MMC. （4） Specific NF-κB inhibitor PDTC could reduce HMGBl-mediated NF-κB activation, and NF-κB p65 protein expression significantly decreased in the HMGB1 ＋ PDTC group compared with HMGB1 group. PDTC down-regula- ted HMGBl-mediated cell proliferation, and PCNA protein expression decreased in HMGB1 ＋ PDTC group. Conclusion NF-κB sig-naling pathway activation mediates the pathogenesis of lupus nephritis and might be significantly correlated with mesangial cell prolifera-tion.

关 键 词：狼疮性肾炎 NF—κB P65 HMGB1 系膜细胞 细胞增殖 

分 类 号：R363[医药卫生—病理学] R593[医药卫生—基础医学]