雷帕霉素对多柔比星诱导的大鼠肾纤维化模型肾组织趋化因子受体CCR7表达的影响

The influence of rapamycin on expression of CCR7 in the rats with renal fibrosis induced by adriamycin

目的观察雷帕霉素(RAP)对多柔比星诱导大鼠的肾纤维化模型中肾组织内趋化因子受体CCR7表达的影响,探讨该药对慢性肾纤维化大鼠肾脏保护作用及可能的机制。方法28只大鼠随机分为:正常对照组(A组,8只)、多柔比星肾病模型组(B组,10只)、RAP治疗组(C组,10只)。实验开始第1、2周的第1天,给予B、C组大鼠多柔比星(4mg/kg)尾静脉注射。自首次注射多柔比星之日起第2周末,C组给予RAP1.5mg/(kg.d)灌胃。首次给予多柔比星后7周末收集24h尿标本后取肾组织标本。BCA法检测24h尿蛋白,Masson染色并在光镜观察肾组织病理变化,使用肾小球硬化指数及肾小管间质损伤指数评估肾脏病变程度;免疫组化检测肾组织内Ⅰ型胶原、CD45和CCR7蛋白表达。结果B组24h蛋白尿排出量明显高于A组[(568±102)mgvs(23±7)mg,P<0.01],光镜观察到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,大量炎症细胞浸润,免疫组化检测Ⅰ型胶原、CD45和CCR7蛋白表达明显高于A组(P<0.01);C组肾小球硬化指数、肾小管间质损伤指数,24h蛋白尿排出量明显低于B组(P<0.01),Ⅰ型胶原、CD45和CCR7蛋白表达显著降低(P<0.01),肾组织病理改变减轻。结论RAP可改善大鼠多柔比星诱导的肾纤维化,机制可能与抑制CCR7受体表达有关。

Objective To investigate the influence of rapamycin （RAP） on the expression of CCR7 and collagen Ⅰin the kidney of adriamycin-induced renal fibrosis rats and to explore its the possible mechanisms.Methods Rats were assigned to three groups randomly：normal control group （group A）,model group （group B） and RAP treatment group （group C）.Rats in group B and C were given RAP 4 mg/kg via tail vein at the first day of the 1st and 2nd week,respectively.Group C received RAP treatment 1.5 mg/（kg·d） orally in the 2 nd week after the first adriamycin injection.The changes of 24 h urine protein and renal pathological were evaluated in the 7 th week after the first administration of adriamycin.The expression of collagen I,leucocyte common antigen （CD45） and chemokine receptor 7 （CCR7） were analyzed by immunohistochemistry.Results In group B,24 h urine protein was significantly increased compared to group A [（568±102）mg vs （23±7） mg,P〈0.01].The proliferation of the mesangial cells,the accumulation of the extracellular matrix and atrophy in or extension of renal tubules were obviously observed in group B.The expression of Collagen I、CD45 and CCR7 protein were also increased notably（P〈0.01）.These changes were signicantly ameliorated by theatment with RAP（P〈0.01）.Conclusion Rapamycin can ameliorate renal fibrosis induced by adriamycin in rats,and the mechanisms may be correlated with the downregulation of CCR7.