狼疮肾炎肾组织核转录因子-κB单核细胞趋化因子-1与CD68的表达及相关分析

目的 对狼疮肾炎(LN)肾组织进行核转录因子-κB(NF-κB)、单核细胞趋化因子(MCP-1)及巨噬细胞特异性抗体(CD68)检测,探讨其与LN肾脏病理及临床指标的关系.方法 应用免疫组织化学二步法检测49例LN肾组织NF-κB、MCP-1及CD68,原位杂交法检测49例LN肾组织NF-κB,并与肾脏病理及临床指标进行分析.结果 ①LN肾组织中NF-κB、MCP-1及CD68表达均比对照组显著升高(P＜0.01);其中Ⅳ型LN肾组织中NF-κB、MCP-1及CD68的表达比非Ⅳ型LN及对照组明显增加(P＜0.01,P＜0.05).原位杂交与免疫组织化学法检测NF-κB差异无统计学意义(P＞0.05).②LN肾组织中,NF-κB的表达与肾组织活动性指数、尿蛋白定量(24 h)及血清肌酐均高于对照组,且三者之间差异有统计学意义(P＜0.01,P＜0.01,P＜0.05);MCP-1与CD68的表达在肾小球和肾小管中仅与肾组织活动性指数(r=0.447,0.532,P＜0.05)、尿蛋白定量(24 h)(r=0.357,0.368,P＜0.05)呈正相关,而与血肌酐之间差异无统计学意义(P＞0.05).结论 NF-κB通过活化MCP-1进一步诱导巨噬细胞可能是LN肾脏损害的原因之一,NF-κB信号途径有望成为抑制巨噬细胞在肾脏局部浸润和增生的一个新的治疗靶点.

Correlation between the expression of nuclear factor-kappa B,monocyte chemoattractant protein-1 and CD68 in lupus nephritis

Objective To observe the expression of nuclear factor-kappa B(NF-κ3)and monocyte chemnattractant protein-1(MCP-1),and the infiltration of mononuclear macrophage CD68 in lupus nephritis (LN).The association between NF-κB,MCP-1 and MΦ with kidney pathology and clinical manifestations is explored.MethodsNF-κB,MCP-1 and MΦ in renal biopsy specimens from 49 cases of LN were detected using immunohistochemical techeniques.Forty-nine cases of renal tissues were examined for NF-κB by in situ hybridization.The relationship between NF-κB,MCP-1 and MΦ with kidney pathology and clinical manifestations were analyzed.Results ①Compared with the control group ,the expression of NF-κB,MCP-1 and MΦ in LN was significantly higher(P＜0.01).The expression of MCP-1 positively correlated with MΦinfiltration and NF-κB(P＜0.01)in glomeruli and renal tubule and renal interstitium of LN.The expression of NF-κB,MCP-1 and the infiltration of MΦ in LN Ⅳ was significandy higher than non LN Ⅳ and the control group(P＜0.01,P＜0.05).There was no significant difference between renal NF-κB positive group and negative groups in the degree of the immunohistochemical and in situ hybridization examination(P＞0.05).②The histological activity index,urine protein volume(24 h)and serum creatinine in LN were significantly higher than the control group(P＜0.01),and the expression of NF-κB in LN was correlated with histological activity index,urine protein volume(24 h)and serum creatinine(P＜0.01,P＜0.01,P＜0.05).MCP-1 and CD68 expression in LN were correlated with histological activity index and urine protein volume(24 h),but not correlated with serum creatinine(P＞0.05).Conclusion NF-κB induced MΦ by activating MCP-1 may be one cause of kidney injury of LN.NF-κB signal pathway may act as a new therapeutic target for MΦinfiltration and proliferation inhibition in kidney.