C-C趋化因子受体2在盐敏感性高血压所致肾脏损害中的作用  

Role of Chemokine Receptor 2 in Renal Damage Induced by Deoxycorticosterone Acetate-salt Hypertension

作　　者：孙邈[1,2] 崔琳[1] 刘卫红[1] 高原[1] 沈思[1] 朱明军[1] 王幼平[1] 

机构地区：[1]河南中医学院第一附属医院中心实验室及心脏中心,郑州450000 [2]河南中医学院中医内科学,郑州450008

出　　处：《中国医学科学院学报》2013年第1期29-35,共7页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(81170243)~~

摘　　要：目的探讨C-C趋化因子受体2(CCR2)在盐敏感性高血压所致肾脏损害中的作用。方法通过切除小鼠左侧肾脏、皮下包埋醋酸脱氧皮质酮(DOCA)和饮用盐水制备盐敏感性高血压小鼠模型,DOCA-盐高血压小鼠分为模型组和CCR2受体阻断剂组,分别皮下注射溶媒和特异性的CCR2受体阻断剂RS504393,对照组小鼠仅左肾切除和给予正常饮用水。检测动脉收缩压、24 h尿白蛋白排泄量、8-异构前列腺素排泄量、肌酐清除率、肾小球纤维样硬化指数、单核/巨噬细胞浸润程度。结果与对照组相比,模型组血压升高、24 h尿白蛋白和8-异构前列腺素排泄量增加、肌酐清除率下降、肾脏有较明显的肾小球纤维样硬化和肾小管间质损害,并伴有明显的单核/巨噬细胞浸润(P<0.05)。RS504393能显著抑制上述异常变化(P<0.05),使各项肾功能和肾形态学指标基本恢复正常,但RS504393对血压无影响。结论 CCR2受体阻断剂可抑制DOCA-盐高血压所致肾脏损害,CCR2受体介导的单核/巨噬细胞浸润在盐敏感性高血压诱导的肾脏损害中发挥重要作用。Objective To determine the role of chemokine receptor 2 （CCR2） in the development of salt-sensitive hypertension-induced renal damage. Methods We investigated the renal damage induced by uninephrectomy and deoxyeorticosterone acetate （DOCA） -salt in mice treated with or without a selective CCR2 antagonist RS504393 for 4 weeks. Sham mice underwent uninephrectomy without receiving DOCA and saline. Systolic blood pressure, urinary excretion of albumin and 8-isoprostane, creatinine clearance, glomerulosclerosis,renal tubulointerstitial injury, and renal monocyte/macrophage infiltration were measured. Results DOCA-sah treatment led to increased systolic blood pressure, increased urinary excretion of albumin and 8-isoprostane, de- creased creatinine clearance, glomeruloselerosis, renal tubulointerstitial injury, and renal monocyte/macrophage in- filtration compared with the sham mice （ P 〈 0.05 ）. All of them were prevented by CCR2 inhibition （ P 〈 0.05 ）. Conclusion Blockade of CCR2 prevents renal damage induced by DOCA-sah treatment, suggesting that CCR2-mediated monocyte/macrophage infiltration may contribute to salt-sensitive hypertension-induced renal injury.

关 键 词：盐敏感性高血压 肾脏损害 C-C趋化因子受体2 阻断剂 单核 巨噬细胞 

分 类 号：R364[医药卫生—病理学]