摘要
目的研究Ig A肾病（IgAN）患者外周血单个核细胞Toll样受体4（TLR4）的表达及血清中趋化因子MCP-1和炎症因子IL-6的水平,探讨TLR4在IgAN发病中可能的作用。方法将在本科经肾组织活检确诊为IgAN的60例患者（排除继发性和遗传性IgAN）根据蛋白尿程度进行分组,分为轻度蛋白尿组（24 h尿蛋白定量≤1.0 g）,中度蛋白尿组（24 h尿蛋白定量1.0~3.0 g）和重度蛋白尿组（24 h尿蛋白定量≥3.0 g）。另取年龄性别相匹配的健康志愿者20例作为健康对照组。分别使用流式细胞仪和Realtime-PCR方法检测外周血单个核细胞（PBMC）中TLR4蛋白和基因的表达,ELISA法检测血清中趋化因子MCP-1和炎症因子IL-6的水平。结果 IgAN组患者PBMC中TLR4的蛋白和基因表达水平以及血清中MCP-1和IL-6的浓度均较健康对照组显著增加（P均〈0.05）。PBMC中TLR4的蛋白和基因表达水平随着蛋白尿的严重程度而逐渐增高。直线相关分析提示PBMC中TLR4 mRNA的表达水平与24 h尿蛋白定量呈显著正相关（r=0.855,P〈0.05）,而与GFR呈负相关（r=-0.735,P〈0.05）。MCP-1和IL-6的水平与PBMC中TLR4 mRNA的表达水平呈显著正相关（r=0.746、0.821,P〈0.05）。结论 IgAN患者PBMC中存在TLR4的表达水平上调,与蛋白尿程度和肾功能水平密切相关。血清中趋化因子MCP-1和炎症因子IL-6的水平也随着PBMC中TLR4的表达水平升高而升高。TLR4可能通过调节机体趋化因子和炎症因子的释放介导了Ig A肾病中的炎症损伤。
Objective To explore the expression of Toll-like receptor 4 in peripheral blood mononuclear cells（ PBMC） and serum concentration of chemokine MCP-1 and inflammation cytokine IL-6 in patients with Ig A nephropathy. Methods A total of 60 patients with IgAN confirmed by renal biopsy were divided into three groups according to 24 h proteinuria,which were mild proteinuria group,morderate proteinuria group and severe proteinuria group. Patients with secondary and hereditary IgAN were excluded. Another 20 healthy volunteers were selected as control group. Protein and gene expression of TLR4 in PBMC were evaluated with flow cytometry and real time-PCR respectively.Levels of MCP-1 and IL-6 were measured by commercial ELISA kit. Results Expression of TLR4 inPBMC and levels of MCP-1 and IL-6 in circulation were significantly higher in Ig AN group than in control group（ P〈0. 05）. Protein and gene expression of TLR4 in PBMC increased with the severity of proteinuria（ P〈0. 05）. The Pearson correlation coefficient analysis suggested that gene expression of TLR4 in PBMC was positively correlated with 24 h urinary protein excretion（ r = 0. 855,P〈0. 05）,but negatively correlated with GFR（ r =- 0. 735,P〈0. 05）. Serum concentration of MCP-1 and IL-6 were positively correlated with gene expression of TLR4 in PBMC（ r = 0. 746,0. 821,P〈0. 05）. Conclusion Expression of TLR4 in PBMC and levels of MCP-1 and IL-6 in circulation are all up-regulated in patients with Ig AN. Expression of TLR4 in PBMC is closely related with the severity of proteinuria and renal function. These findings suggest that TLR4 may mediate inflammatory injury of Ig AN by releasing inflammation cytokine and chemokine.
出处
《实用临床医药杂志》
CAS
2016年第19期23-27,共5页
Journal of Clinical Medicine in Practice
基金
上海交通大学医学院附属新华医院科研基金资助(12QYJ06)
