摘要
目的:探讨重组人高迁移率族蛋白B1(High mobility group box1,HMGB1)刺激伴肾脏损害和不伴肾脏损害的系统性红斑狼疮患者外周血单个核细胞后自噬相关蛋白——微管相关蛋白1轻链3(LC3)的两个亚型LC3Ⅱ/Ⅰ的表达情况,以及重组人HMGB1刺激对SLE患者外周血单个核细胞增殖的影响。方法:Western blot比较1μg/ml重组人HMGB1蛋白刺激伴肾脏损害与不伴肾脏损害的系统性红斑狼疮患者外周血单个核细胞0、6、24、48 h后自噬相关蛋白LC3Ⅱ/Ⅰ的表达情况。CCK-8法检测1μg/ml HMGB1刺激72 h对SLE患者外周血单个核细胞增殖的影响。应用SPSS17.0进行数据分析。结果:Western blot结果显示:HMGB1时间依赖性地引起SLE患者外周血单个核细胞中自噬相关蛋白LC3Ⅱ/Ⅰ表达上调(P<0.05)。伴肾脏损害组与不伴肾脏损害组相比,自噬水平的增加更为明显。1μg/ml HMGB1明显抑制SLE患者PBMC的增殖(P<0.001)。结论:HMGB1可以使SLE尤其是伴肾脏损害患者外周血单个核细胞发生细胞自噬,参与SLE甚至狼疮肾炎的发病。提示针对HMGB1的单克隆抗体或细胞自噬调节剂可能成为SLE新的治疗靶点。
Objective:To stimulate the PBMCs of systemic lupus erythematosus patients with recombinant human high mobility group box1 (HMGB1) protein,observe the effect of HMGB1 on the expression of LC3Ⅱ/Ⅰ protein in active lupus nephritis and inactive lupus nephritis patients.Evaluate the effect of recombinant human high mobility group box 1 ( HMGB1 ) on the proliferation of PBMCs in patients with SLE.Methods:Western blot was used to detect the expression of LC 3II/I protein in PBMCs of active lupus nephritis and inactive lupus nephritis patients after stimulated by 1 μg/ml HMGB1 for 0,6,24 and 48 h.CCK-8 assay was used to detect the effects of PBMCs proliferation in patients with SLE after 1 μg/ml HMGB1 stimulation 72 hours.The statistical software SPSS17.0 was used to analyzed the results.Results: Western bolt showed an increasing expression of LC 3Ⅱ/Ⅰ protein in SLE patients after stimulated by HMGB1 ( P〈0.05 ) , and this effect was time dependent.Compared with inactive lupus nephritis group , the increasing level of autophagy in active lupus nephritis group was more obviously.1 μg/ml HMGB1 could inhibit the proliferation of PBMCs in patients of SLE significantly ( P〈0.001 ).Conclusion: HMGB1 may promote autophagy in SLE especially patients with active lupus nephritis and involved in the pathogenesis of SLE and lupus nephritis.Monoclonal antibodies targeting to HMGB 1 or modulators of mam-malian autophagy may provide new way for the treatment of SLE especially LN.
出处
《中国免疫学杂志》
CAS
CSCD
北大核心
2014年第7期942-945,949,共5页
Chinese Journal of Immunology
基金
黑龙江省自然科学基金重点项目(ZD200814-01)
关键词
红斑狼疮
系统性
重组HMBG1
自噬
LC3
Systemic lupus erythematosus
Recombinant human high mobility group box 1 protein
Autophagy
LC3