MRL/lpr小鼠肾组织MCP-l表达及MMF对其表达的影响和相关机制研究

Study of the expression of MCP-1 in the lupus nephritis mice and the effect of mycophenolate mofetil

目的:检测MRL/lpr狼疮小鼠肾组织单核细胞趋化蛋白-1(MCP-1)表达及探讨霉酚酸酯(MMF)对其影响和相关机制,研究MMF对MRL/lpr狼疮小鼠的治疗作用。方法:MRL/lpr狼疮小鼠分为对照组和治疗组两组。观察肾组织病理学改变及其MCP-1、CD14和蛋白激酶C(PKC)等的表达以及尿蛋白、抗ds-DNA抗体水平的变化。结果:对照组小鼠肾小球基底膜增厚,系膜基质增多,肾组织MCP-1表达上调,CD14+细胞数明显增多,伴尿蛋白及抗ds-DNA抗体水平增加。治疗组小鼠肾组织MCP-1表达减少,CD14+细胞数减少,尿蛋白和抗ds-DNA抗体水平减少,且肾小球MCP-1与其PKC表达水平及肾小球CD14+细胞数、尿蛋白水平呈直线相关关系。结论:MMF对MRL/lpr小鼠自发狼疮肾炎具有治疗作用,其机制可能通过抑制PKC通道激活减少小鼠肾组织MCP-1的表达,从而减少肾组织单核细胞的浸润,减轻肾脏损害。

Objective To study the protective effect of mycophenolate mofetil （MMF） on MRL/lpr mice and it＇ s influence to the expression of monocyte chemoattractant protein-1 （ MCP- 1 ） in the renal tissues, and to explore the underlying molecular mechanisms. Methods MRL/lpr mice were divided into two groups： MMF group and control group. The levels of urinary protein and anti-dsDNA antibody, the change of pathology and the expression of MCP- 1, CD14 and protein kinase C（PKC） in renal tissues were observed. Results Compared to the ones in the control group, mice treated with MMF had lower levels of urinary protein and anti-dsDNA antibody（ P 〈0.01 ）. The ratio of mesangial/ glomerular area, glomerular basement membrane significantly decreased after treatment. Compared to the ones in the control group,the expression of MCP-1 ,the number of CD14 positive cells, the level of urinary protein and the level of anti-dsDNA antibody in renal tissues significantly decreased, and the expression of MCP- 1 had linear correlation with the number of CD14 positive cells and the level of urinary protein in MMF group . Immunological results revealed that expression of PKC increased in control group compared to those of the MMF group and had a linear correlation with the expression of MCP-1 in the renal cortex of mice. Conclusion The number of monocytes in the tissues of MRL/lpr mice is ascending and is in part ehemotaxised by MCP-1 which is expressed in renal tissue. MMF have good efficacy in the treatment of MRL/lpr mice,it can reduce the expression of MCP-1 in the renal tissue. The descensive MCP-1 is possibly caused by the reduction of PKC in renal tissues. So it ameliorates tubulointerstitial infiltration of inflammatory cells and glomerular injuries. The expression of PKC is reduced in the MMF group.