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

作　　者：李桂英[1] 路新卿[1] 刘淑霞[2] 李玲[1] 张增海[1] 徐建萍[3] 李彤中[1] 李英[4] 

机构地区：[1]河北工程大学附属医院肾内科,河北邯郸056029 [2]河北医科大学病理教研室,石家庄050017 [3]邯郸市中心医院免疫风湿科,河北邯郸056002 [4]河北医科大学第三医院肾内科,石家庄050017

出　　处：《中国中西医结合杂志》2011年第12期1685-1689,共5页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：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)

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。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（P0.01）.The aforesaid indices all obviously decreased after medication in the Chinese medicine group and the hormone group（P0.05）.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 P0.01）.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.

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 

分 类 号：R593.242[医药卫生—内科学]