HMGB1和TNFAIP3在狼疮性肾炎系膜细胞增殖中的作用  

Role of HMGB1 and TNFAIP3 involved in mesangial cell proliferation of lupus nephritis

作　　者：张玮[1] 杨冉[1] 郭惠芳[2] 封晓娟[1] 魏群[3] 张玉[2] 王奕卓 李金泽[1] 刘淑霞[1] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017 [2]河北医科大学第二医院免疫风湿科,河北石家庄050000 [3]河北省人民医院医院感染管理科,河北石家庄050000

出　　处：《中国药理学通报》2017年第8期1109-1113,共5页Chinese Pharmacological Bulletin

基　　金：河北省自然科学基金青年基金资助项目(No H2015206449);河北省卫生厅重点科技研究计划(No ZD20140034);河北省大学生创新创业训练计划(No201510089038)

摘　　要：目的初步探讨高迁移率族蛋白1(high mobility group protein B1,HMGB1)和肿瘤坏死因子α诱导蛋白3(tumor necrosis factorα-induced protein-3,TNFAIP3)在狼疮性肾炎(lupus nephritis,LN)患者和人类肾小球系膜细胞(human mesangial cell,HMC)增殖中的作用及机制。方法收集Ⅳ型LN患者的肾穿样本,采用免疫荧光和免疫组化技术检测肾小球细胞中HMGB1、TNFAIP3及IκBα蛋白表达水平;运用人重组HMGB1为刺激物刺激HMC,采用Brd U参入技术检测细胞增殖水平,并用Western blot技术检测TNFAIP3、IκBα及p65表达水平。结果与对照组相比,LN患者肾小球细胞中HMGB1及TNFAIP3蛋白表达升高,IκBα表达水平降低;体外实验证实,人重组HMGB1刺激HMC后,细胞增殖水平明显升高,同时在HMGB1刺激30 min后,与对照组相比,TNFAIP3的蛋白表达水平明显升高(P<0.05),而IκBα蛋白表达水平降低(P<0.05),随后p65蛋白表达明显升高(P<0.05)。结论 HMGB1和TNFAIP3可能通过活化NF-κB信号通路促进LN系膜细胞的过度增殖。Aim To investigate the mechanism of high mobility group protein B1（ HMGB1） and tumor necrosis factor α-induced protein-3（ TNFAIP3） involved in cell proliferation in lupus nephritis（ LN） patients and human mesangial cells（ HMC）. Methods Immunofluorescence and immunohistochemistry technique were employed to detect HMGB1,TNFAIP3 and IκBα expression levels in glomerular cells of type Ⅳ LN patients. Brd U incorporation technology was used to detect cell proliferation level in HMC after stimulated by recombinant HMGB1. TNFAIP3 and IκBα expression levels in HMC were detected after HMGB1 stimulation by Western blot. Results The expression levels of HMGB1 and TNFAIP3 were increased in LN patients,while IκBα was decreased. HMC proliferation levels increased significantly after HMGB1 stimulation. At the same time,30 minutes after HMGB1 stimulation,the expression level of TNFAIP3 was significantly increased（ P〈0. 05）,while IκBα decreased（ P〈0. 05）and then p65 increased significantly（ P〈0. 05）,compared with control group. Conclusion HMGB1 and TNFAIP3 are probably involved in mesangial cell proliferation by activating of NF-κB signaling pathways in LN pathogenesis.

关 键 词：狼疮性肾炎 HMGB1 TNFAIP3 细胞增殖 人系膜细胞 蛋白表达 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]