糖尿病肾病患者尿MCP-1的变化及ACEI及AngⅡ受体拮抗剂对其影响

Effects of angiotension Ⅱ convertase inhibitor and angiotension Ⅱ receptor antagonist on urine monocyte chemoattractant protein-1 in human diabetic nephropathy

目的 探讨血管紧张素Ⅱ (AngiotensionⅡ ,AngⅡ )转换酶抑制剂 (Angiotensio Convertingenzymeinhibitor ,ACEI)及AngⅡ受体拮抗剂对糖尿病肾病 (Diabetesnephropathy ,DN)单核细胞趋化蛋白 1(Monocytechemoattractantpro tein 1,MCP 1)影响及临床意义。方法 观察MCP 1的变化 ,采用免疫组化和原位杂交检测人DN肾组织MCP 1蛋白和mRNA表达 ,并用免疫组化检测CD68;对DN患者采用随机给予苯那普利和氯沙坦治疗量 ,采用ELISA法检测治疗前后尿液MCP 1水平。结果 DN肾小管间质MCP 1表达明显增高 (P <0 .0 1) ,小管间质病变愈重 ,MCP 1表达愈高 (P <0 .0 1)。DN肾小球MCP 1表达较正常对照明显增高 (P <0 .0 5 ) ,各级肾小球病变间无明显差异。DN肾小管间质CD68表达明显增高 (P <0 .0 1) ,各级小管间质病变间差异明显 (P <0 .0 1)。DN肾小球CD68表达较正常对照明显增高 (P <0 .0 5 ) ,各级肾小球病变间无明显差异。DN尿液MCP 1水平明显较正常对照组增高 (P <0 .0 1) ,与肾小管间质MCP 1表达呈正相关 ,服用苯那普利和氯沙坦均可降低尿液MCP 1水平。结论 DN患者肾组织内MCP 1表达与肾病变发生发展密切相关 ,尤其与肾小管间质病变的形成有关 ,血管紧张素Ⅱ及AngⅡ受体拮抗剂可能通过抑制单核

Objective To study the effects of angiotension Ⅱ convertase inhibitor and angiotension Ⅱ receptor antagonist on monocyte chemoattractant protein 1(MCP 1) and its significance in human diabetic nephropathy. Methods The expression of MCP 1 was detected by immunohistochemical staining and in situ hybridization. The expression of CD68 was also examined by immunohistochemical staining. Diabetic nephropathy(DN) patients were administered with benazepril and losartan at random therapeutic doses. Pretreatment and post treatment urinary MCP 1 levels were measured by enzyme linked immunosorbent assay(ELISA). Results The expression of MCP 1 in tubulointerstitial lesion in DN patients increased significantly( P <0.01) in a severity dependent manner( P <0.01). The expression of MCP 1 in glomerulus in DN patients increased significantly( P <0.05). There was no difference between different degrees of glomerular lesion. The results of CD68 were the same as those of MCP 1. Urinary levels of MCP 1 in DN patients were significantly higher than those in control. Urinary levels of MCP 1 were positively correlated with the expression of MCP 1 in renal tubule. After treatment with benazepril and losartan, urinary levels of MCP 1 decreased significantly. Conclusion The expression of MCP 1 may be involved in the development of DN, especially in the formation of tubulointerstitial lesions. Angiotension Ⅱ convertase inhibitor and angiotension Ⅱ receptor antagonist may improve tubulointerstitial lesion possibly through the inhibition of monocyte/macrophage recruitment and activation.