纤维细胞在大鼠多柔比星慢性肾损害模型肾纤维化过程中的作用  

Effect of fibrocytes on the progressive renal fibrosis induced by adriamycin Effect of fibrocytes on the progressive renal fibrosis induced by adriamycin

作　　者：王显[1] 张伯科[1] 沈雯雯[1] 周琪[1] 

机构地区：[1]安徽医科大学第一附属医院肾脏内科,合肥230022

出　　处：《中华肾脏病杂志》2010年第4期279-283,共5页Chinese Journal of Nephrology

基　　金：安徽省自然科学基金（070413074）

摘　　要：目的 以多柔比星慢性肾损害大鼠为对象,探讨纤维细胞及其趋化因子受体7（CCR7）在肾纤维化中的作用.方法 雄性SD大鼠52只,随机分为对照组（n=20）、模型组（n=32）.实验开始第1、2周第1天,模型组重复给予多柔比星（4 mg/kg）尾静脉注射,对照组给予等量生理盐水,首次给药后第4、7、10、13周末取血、尿检测生化指标;并于对照组和模型组分别随机选取5只和8只大鼠处死留取肾组织,通过Masson染色观察肾脏病理变化.使用肾小球硬化指数（GSI）和肾小管间质损伤指数（TII）评估肾脏病变程度;免疫组化检测CD45、Ⅰ型胶原和CCR7表达.结果 与对照组相比,第7周末模型组血三酰甘油水平（mmol/L）升高（2.57±1.19比0.76±0.11,P〈0.01）、血总胆固醇水平（mmol/L）升高（6.79±1.47比1.29±0.27,P〈0.01）,血清白蛋白水平（g/L）降低（21.4l±2.11比34.64±0.96,P〈0.01）;24 h尿蛋白排出量（mg）明显增加（568±102比21±6,P〈0.01）;肾小球系膜基质明显增多,肾小管多灶性萎缩和扩张,管腔内可见蛋白管型.GSI及TII随时间延长逐渐升高（P〈0.05）.连续切片观察肾间质出现CD45、Ⅰ型胶原双阳性细胞.CD45和CCR7阳性细胞第7周数量最多,后逐渐减少（P〈0.01）.结论 纤维细胞可能参与肾纤维化过程,在早期发挥作用,其由外周血迁移到组织可能与CCR7有关.Objective To investigate the effect of fibrocytes and chemokine recepter 7 （CCR7） on the process of renal fibrosis induced by adriamycin in rats. Methods Male Sprague-Dawley （SD） 8 weeks old rats （n=52） were divided into two groups randomly, normal control group （CG, n= 20） and model group （MG, n=32）. MG rats were injected with 4 mg/kg of adriamycin via tail vein on the first day of the 1st and 2nd week, respectively, while CG rats received 0.9% sodium chloride solution injection of equal volume at the same time. The urine and serum samples were measured at the end of 4, 7, 10 and 13 weeks after the first administration of adriamycin to observe biochemical changes, while the renal tissue of rats was obtained to evaluate renal histological and uhrastructural changes by glomerulosclerosis index and tubulointerstitial index, and to analyze the expression of CD45, collagen I and CCR7 by immunohistochemistry. Results Compared with CG, levels of 24 h urine protein excretion rate （mg, 568±102 vs 21±6, P〈0.01）, serum cholesterol （CHO, mmol/L, 6.79±1.47 vs 1.29±0.27, P〈0.01） and triglyceride （TG, mmol/L, 2.57＋1.19 vs 0.76±0.11, P〈0.01） increased significantly, whereas serum albumin （Alb, g/L,21.41±2.11 vs 34.64±0.96, P 〈0.01）decreased significantly in the 7th week in MG. The proliferation of mesangial cells, the accumulation of the extracellular matrix and atrophyin or extension of renal tubules in MG were more remarkable than those in CG. There were some cells which expressed CD45 and collagen I simultaneously in the serial sections of renal tissue and renal eortical interstitium in MG. Interstitial infiltration of CD45 ＋ or CCR7 ＋ cells appeared in the 4th week, reached a maximum in the 7th week （P〈0.01） and gradually decreased afterward. Conclusions Fibrocytes may be involved in the earlier stage of kidney fibrosis. The immigration of this population from peripheral blood to renal lesion site is possible to be associated with CCR7 protein.

关 键 词：多柔比星 纤维化 受体 趋化因子 纤维细胞 

分 类 号：R692[医药卫生—泌尿科学]