目的:探讨NF-κB信号途径在小鼠狼疮性肾炎发病中的可能作用。方法:选取16周龄的雄性BXSB小鼠(狼疮性肾炎模型组)和同周龄C57BL/6小鼠(正常对照组)作为研究对象,透射电镜和PAS染色观察肾组织的超微结构形态改变;RT-PCR技术检测小鼠全血中HMGB1mRNA的表达变化。采用ELISA方法检测血清中HMGB1蛋白浓度;免疫组织化学检测肾组织中HMGB1和PCNA蛋白的表达变化;Western blot和流式细胞术检测肾组织中RAGE、p-NF-κB和IκB蛋白的表达。结果:16周时,与正常的C57BL/6小鼠相比,BXSB小鼠血清中BUN水平及尿中微球白蛋白水平明显升高;与正常的C57BL/6小鼠相比,BXSB小鼠全血中HMGB1mRNA水平和血清中HMGB1蛋白浓度明显升高;16周时,与正常的C57BL/6小鼠相比,BXSB基底膜明显增厚,部分足突融合,内皮细胞下可见团块状电子致密物沉积;与正常的C57BL/6小鼠相比,BXSB小鼠肾组织的肾小球中可见较多的PCNA阳性表达,肾小管上皮细胞核内也可见少量的表达;BXSB小鼠肾组织中HMGB1蛋白表达升高,HMGB1蛋白尤其在细胞增生明显而肥大的肾小球呈高表达,主要位于细胞浆和细胞外;而在C57BL/6小鼠肾脏组织中以小管细胞核表达为主;与对照组相比,BXSB小鼠肾组织p-NF-κB和RAGE蛋白表达明显升高;而IκB蛋白表达明显降低;HMGB1蛋白与p-NF-κB蛋白表达呈显著正相关(r=0.833,P=0.000);p-NF-κB蛋白与RAGE蛋白表达呈显著正相关(r=0.621,P=0.018);HMGB1蛋白与RAGE蛋白表达呈显著正相关(r=0.848,P=0.000);p-NF-κB蛋白与IκB蛋白表达呈显著负相关(r=-0.759,P=0.002)。结论:HMGB1在小鼠狼疮性肾炎中的致炎作用可能部分通过结合其受体RAGE,激活NF-κB信号途径,促进肾小球固有细胞的增生,从而导致增生性肾小球肾炎形成而实现的。 Objective: To investigate the possible role of NF-κB pathway in the pathogenesis of lupus nephritis in mice. Methods: 16-week-old male BXSB mice (lupus nephritis model group) and the same age-old C57BL / 6 mice (normal control group) were selected as research objects. The ultrastructural changes of renal tissues were observed by transmission electron microscopy and PAS staining The expression of HMGB1 mRNA in whole blood of mice was detected by RT-PCR. Serum levels of HMGB1 protein were detected by ELISA. The expression of HMGB1 and PCNA protein in renal tissues was detected by immunohistochemical staining. The expressions of RAGE, p-NF-κB and IκB protein in renal tissues were detected by Western blot and flow cytometry. Results: Compared with normal C57BL / 6 mice, BUN level and urinary albumin level in BXSB mice were significantly increased at 16 weeks. Compared with normal C57BL / 6 mice, BXSB mice The levels of HMGB1 mRNA and serum HMGB1 protein in whole blood were significantly increased at 16 weeks. Compared with normal C57BL / 6 mice, the thickness of BXSB basal membrane was thick at the 16th week, Dense deposits; compared with normal C57BL / 6 mice, BXSB mice showed more positive expression of PCNA in renal glomerulus and a small amount of expression in renal tubular epithelial cells. In BXSB mice, The expression of HMGB1 protein was elevated in the glomeruli with hypertrophy and hypertrophy, especially in the cytoplasm and extracellular domain. HMGB1 protein was mainly expressed in the tubular nucleus in C57BL / 6 mice. Compared with the control Compared with the control group, the expression of p-NF-κB and RAGE in renal tissues of BXSB mice was significantly increased, but the expression of IκB was significantly decreased (P <0.05); the expression of HMGB1 protein was positively correlated with the expression of p-NF- 0.000). There was a significant positive correlation between p-NF-κB protein and RAGE protein (r = 0.621, P = 0.018) White expression was a significant positive correlation (r = 0.848, P = 0.000); showed a significant negative correlation protein p-NF-κB and the expression of IκB (r = -0.759, P = 0.002). Conclusion: The proinflammatory effect of HMGB1 in mouse lupus nephritis may be partly mediated by the binding of its receptor RAGE, activation of NF-κB signal pathway, promotion of proliferation of glomerular innate cells and formation of proliferative glomerulonephritis of.