Li Gui-ying, Lu Xin-qing, Liu Shu-xia
Department of Nephrology, The Affiliated Hospital of Hebei Engineering University, Hebei.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2011 Dec;31(12):1685-9.
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-kappaB) 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-kappaB 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.
The 24-h urine protein level, serum ds-DNA antibody content, protein and mRNA expressions of MCP-1, NF-kappaB 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-kappaB 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).
LG possibly played renal protection by down-regulating NF-kappaB-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.
研究狼疮平颗粒(LG)是否可通过抑制核因子κB(NF-κB)信号通路下调单核细胞趋化蛋白-1(MCP-1)表达,从而对BXSB狼疮性肾炎(LN)小鼠发挥肾脏保护作用。方法将18只11周龄雄性BXSB LN小鼠随机分为3组,即模型组、激素组和中药组,每组6只。分别给予各组小鼠灌胃生理盐水、甲泼尼龙和LG。另取6只同年龄C57BL/6雄性小鼠作为正常对照组,给予灌胃生理盐水。所有小鼠均每日给药1次,连续给药4周。检测24小时尿蛋白。采用RT-PCR和Western blot检测肾组织中MCP-1的mRNA和蛋白表达。采用免疫组化法检测肾组织中NF-κB p65的表达。采用PAS染色计数肾组织的活动指数(AI)。采用ELISA检测双链DNA抗体含量。分析上述指标之间的相关性。
模型组24小时尿蛋白水平、血清双链DNA抗体含量、MCP-1蛋白和mRNA表达、NF-κB p65表达水平及AI计数均明显高于正常对照组(P<0.01)。中药组和激素组给药后上述指标均明显降低(P<0.05)。所有LN小鼠的MCP-1蛋白表达水平与MCP-1 mRNA、NF-κB p65、AI、24小时尿蛋白及双链DNA抗体均呈正相关(r=0.984、0.936、0.887、0.698、0.679,均P<0.01)。
LG可能通过下调NF-κB介导的MCP-1表达水平发挥肾脏保护作用。MCP-1在LN的发生发展中起重要作用,是LN治疗的理想靶点之一。