狼疮平颗粒通过核因子κB信号途径下调BXSB狼疮肾炎小鼠肾组织MCP-1表达

Langchuangping Granule Down-regulated Monocyte Chemoattractant Protein-1 via Suppressing Nuclear Factor kappa B Signaling Pathway in BXSB Lupus Nephritis Mice

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中文关键词: 单核细胞趋化蛋白-1 核因子κB 狼疮平颗粒狼疮肾炎

英文关键词:monocyte chemoattractant protein-1 nuclear factor kappa B Langchuangping Granule lupus nephritis

基金项目:河北省科技厅资助项目(No.10276105D-68);邯郸市科技局资助项目(No.1023108102)

作者	单位
张增海	河北医科大学病理教研室
徐建萍	邯郸市中心医院免疫风湿科
路新卿	河北工程大学附属医院肾内科
刘淑霞	河北工程大学附属医院肾内科
李英	河北医科大学第三医院肾内科
李彤中	河北工程大学附属医院肾内科
李玲	河北医科大学病理教研室
李桂英	河北工程大学附属医院肾内科

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中文摘要:

目的研究狼疮平颗粒是否可以通过下调核因子κB(NF-κB)信号途径抑制单核细胞趋化蛋白-1(monocyte chemoattractant protein l,MCP-1)的表达而发挥对狼疮肾炎(lupus nephritis,LN)小鼠的肾脏保护作用。方法将18只雄性11周龄BXSB LN小鼠随机分为模型组、激素组和中药组,每组6只,分别给予生理盐水、甲泼尼龙、狼疮平颗粒灌胃;另选6只同周龄的雄性C57BL/6小鼠作为正常组,给予生理盐水灌胃,均每天1次,连续4周。测定24 h尿蛋白量;分别采用RT-PCR、Western blot检测肾组织中MCP-1 mRNA和蛋白表达;免疫组化法检测肾组织NF-κB p65表达;PAS染色做肾组织病理活动性指数(activity index,AI)计分;ELISA法检测ds-DNA抗体含量;分析上述指标间的关系。结果模型组24 h尿蛋白水平、血清ds-DNA抗体含量、MCP-1蛋白及mRNA表达水平、NF-κB p65表达水平、AI计分均较正常组明显升高(P<0.01)。用药后中药组与激素组上述指标均明显降低(P<0.05)。LN小鼠MCP-1蛋白表达水平与其mRNA表达水平、NF-κB p65表达水平、AI计分、24 h尿蛋白定量及ds-DNA抗体含量均呈正相关(r=0.984、0.936、0.887、0.698、0.679,P<0.01)。结论狼疮平颗粒可能通过抑制NF-κB的核转位降低MCP-1水平而发挥肾脏保护作用。MCP-1在LN的发生和发展过程中起重要作用,是LN理想的治疗靶位之一。

英文摘要:

Objective To study whether Langchuangping Granule(LG) could exert its renal protection by down-regulating monocyte chemoattractant protein-1(MCP-1) via suppressing nuclear factor kappa B(NF-κB) signaling pathway in BXSB lupus nephritis(LN) mice.Methods Eighteen male 11-week-old BXSB LN mice were randomly divided into three groups,i.e.,the model group,the hormone group,and the Chinese medicine group,6 in each.They were administered by gastrogavage with normal saline,methylprednisolone,and LG,respectively.Another six C57BL/6 male mice of the same age was taken as the normal control group,which was administered with normal saline by gastrogavage.All mice were treated once daily,for 4 successive weeks.The 24-h urine protein was determined.The mRNA and protein expressions of MCP-1 in the renal tissue were detected using RT-PCR and Western blot.The expression of NF-κB p65 in the renal tissue was detected using immunohistochemical assay.Activity index(AI) of the renal tissue was counted using PAS stain.The content of ds-DNA antibody was detected using ELISA.The correlations of the aforesaid indices were analyzed.Results The 24-h urine protein level,serum ds-DNA antibody content,protein and mRNA expressions of MCP-1,NF-κB p65 expression level,and AI count were obviously higher in the model group than in the normal control group(P<0.01).The aforesaid indices all obviously decreased after medication in the Chinese medicine group and the hormone group(P<0.05).MCP-1 protein expression level was positively correlated with MCP-1 mRNA,NF-κB p65,AI,24-h urine protein,and ds-DNA antibody of all LN mice(r=0.984,0.936,0.887,0.698,0.679,all P<0.01).Conclusions LG possibly played renal protection by down-regulating NF-κB-mediated MCP-1 expression levels.MCP-1 played important roles in the occurrence and development of LN,being one of ideal targets for LN treatment.

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