单核细胞趋化蛋白-1在一氧化氮缺乏性高血压肾损害大鼠中的作用

The Role of MCP-1 in Hypertensive Renal Injury of NO-deficient Rat

目的研究单核细胞趋化蛋白-1(MCP-1)在一氧化氮(NO)缺乏性高血压肾损害大鼠中的作用。方法持续给予大鼠NO合酶抑制剂N-硝基-L-精氨酸甲酯(N-Nitro-L-Argininemethyl easter,L-NAME)造成高血压性肾损害大鼠模型(高血压组,n=10),同时选择正常大鼠作对照组(n=10)。8周后在普通光学显微镜下观察肾脏病理变化;观察24 h尿蛋白、尿β2微球蛋白,血清肌酐(Cr),血清和肾组织血管紧张素Ⅱ(AngⅡ)的变化。采用West-ern blotting分析MCP-1蛋白在肾脏表达的差异。结果与对照组比较,8周时高血压组24 h尿蛋白、尿β2微球蛋白,血清肌酐明显增加;普通病理分析发现肾小球硬化指数、间质纤维化指数明显升高;肾脏局部AngⅡ(96.2±18.3 vs 45.3±14.6,P<0.01)、MCP-1水平(3.68±0.25 vs 1.76±0.34,P<0.05)明显升高。结论 MCP-1在NO缺乏所致的高血压性肾损害中发挥着重要的作用,其机制可能与AngⅡ-MCP-1-细胞外基质(ECM)有关。

Objective To study the role of MCP-1 in hypertensive renal injury of NO-deficient Rat.Methods The model of NO-deficient hypertesive renal injury rat was made by giving heavy dose （N-Nitro-L-Argininemethyl easter,L-NAME）（hypertension group,n=10）.Rats were sacrificed after 8 weeks.The renal tissues pathologic change was investgated with light microscope.24 h urinary protein（Up） and β2-microglobucin（β2-m） exeretion were measured.The level of Cr was measured in plasma.The level of angiotensin Ⅱ（AngⅡ） were measured in plasma and renal tissue.The difference of monocyte chemoattractant protein-1（MCP-1） was compared with control group in renal tissue through western blotting.Results As compared to control group,Up and β2-m showed significantly increased at week 8 in hypertension group;Glomerulosclerosis and interstitial fibrosis index elevated apparently in renal tissue of hypertension group;AngⅡ（96.2±18.3 vs 45.3±14.6,P〈0.01） and MCP-1（3.68± 0.25 vs 1.76±0.34,P〈0.05）stayed significant high level in renal tissue of hypertension group.Conclusions MCP-1 plays an important role in the development of hypertensive renal injury induced by NO-deficient,and AngⅡ-MCP-1-ECM axis maybe a major pathological feature in the modle.