霉酚酸酯对糖尿病肾组织炎性因子表达的抑制作用

Anti-inflammation effect of mycophenolate mofetil in diabetic nephropathy

目的探讨霉酚酸酯(MMF)在糖尿病肾组织中发挥抗炎作用及其机制。方法MMF治疗2型糖尿病大鼠,观察肾组织单核/巨噬细胞浸润,及转录因子(NF)-κB p65、神经生长因子表达的变化;不同浓度的霉酚酸干预高糖环境下培养的肾小球系膜细胞,测定细胞间粘附分子(ICAM)-1、单核细胞趋化蛋白(MCP)-1及神经生长因子(NGF)表达的变化。结果MMF治疗能显著改善糖尿病大鼠肾功能,伴肾小球NF-κB p65活性明显下降,NGF表达水平明显降低,单核/巨噬细胞浸润显著减轻。霉酚酸对高糖诱导的肾小球系膜细胞ICAM-1、MCP-1和NGF高表达有显著的抑制作用。结论MMF很可能通过降低NF-κB活性,间接抑制炎性因子表达、炎症细胞浸润。霉酚酸对高糖环境下肾小球系膜细胞ICAM-1、MCP-1和NGF的高表达有显著抑制作用。

Objective To investigate anti-inflammatory mechanisms of MMF in diabetic renal tissue. Methods Type 2 diabetic rats were treated with MMF,and expression of NF-KB p65 ,NGF and CD68 were studied in renal tissue. High glucose（ 30 mmol/L）concentration was used to induce high expression of ICAM-1 ,MCP-1 and NGF in rat MCs, and all indexes were detected as MPA at different doses. Results （ 1 ） MMF depressed the expression of NF-KB p65 ,NGF and CD68 （P 〈0.01 ） in renal issue of DM rats. （2） High expression of ICAM-1 ,MCP-1 and NGF in MCs induced by high glucose was decreased when mycophenolic acid was added. （3） Minimal dose （0.1 μmol/L） MPA can depress expression of inflammatory factors in MCs in vitro, but concentration multiplication of MPA did not significantly strengthen the function above. Conclusion （ 1 ） The protective effects of MMF on diabetic renal tissues was associated with down-regulation of expressions of inflammatory cytokines ,likely mediated by its anti-inflarmnatory action through inhibition of NF-KB activation. （2） MPA could depress high expression of ICAM-1, MCP-1 and NGF induced by high glucose in mesangial cell in vitro.