CCR2与盐性敏感性高血压小鼠肾脏损害的相关性研究

The relevant research of chemokine renal damage caused by deoxycorticosterone acetate-salt hypertension

目的:探究C-C趋化因子受体2(C-C chemokine receptor 2,CCR2)在盐性敏感性高血压小鼠肾脏损害中的作用。方法:先切除小鼠的左侧肾脏,并将醋酸脱氧皮质酮包埋于皮下和饮用盐水以制备盐敏感性高血压小鼠模型,用随机数表法将盐敏感性高血压小鼠分为CCR2受体阻断剂组和模型组,并分别在其皮下注射特异性的CCR2受体阻断剂RS504393和溶媒。对照组小鼠仅给予正常饮用水和左肾切除,记录和比较小鼠的单核/巨噬细胞浸润程度、肾小球纤维样硬化指数、肌酐清除率、8-异构前列腺素排泄量、24h尿白蛋白排泄量、动脉收缩压等。结果:相比于对照组,模型组小鼠的肌酐清除率下降、血压升高。8-异构前列腺素和24h尿白蛋白排泄量增加,肾脏有明显的肾小管间质损害和肾小球纤维样硬化,单核/巨噬细胞浸润明显(P<0.05),而RS504393能够明显抑制上述病理变化(P<0.05),但不影响血压。结论:在盐敏感性高血压诱导的肾脏损害中,单核/巨噬细胞在CCR2受体介导下发挥了总要作用,而CR2阻断剂可抑制醋酸脱氧皮质酮-盐敏感性高血压所诱导的肝脏损害。

Objective： To discuss the role of chemokine renal damage caused by deoxycorticosterone acetate-salt hyper tension. Methods： The mice after undergoing uninephrectomy were divided into three groups randomly. One group was treated by deoxycorticosterone acetate and saline, and one group was treated by deoxycorticosterone acetate with a selective CCR2 an- tagonist RS504393, while sham group only underwent uninephrectomy. Glomerulosclerosis, 8-isoprostane and urinary excre- tion of albumin, creatinine clearance, Systolic blood pressure, renal monocyte/macrophage infihration as well as renal tubu-lointerstitial injury were recorded and analyzed. Results： Compared with the sham mice, deoxycorticosterone acetate-salt hyper- tension led to glomerulosclerosis, significantly decreased creatinine clearance, increased urinary excretion of 8-isoprostane and albumin, and increased systolic blood pressure, renal monocyte/macrophage infiltration as well as renal tubulointerstitial injury （P〈0.05）, while CCR2 could significantly inhibit all of these changes （P〈0.05）. Conclusions： Renal damage caused by de- oxycorticosterone acetate-salt hypertension can be prevented by blockade of CCR2, which indicates that renal injury caused by hypertension maybe due to infiltration of monocyte/macrophage mediated by CCR2.