阿霉素肾病大鼠肾组织中血管形成素样蛋白3表达与蛋白尿及高脂血症的关系  

Expression of ANGPTL3 in kidney and its relationship to proteinuria and hyperlipidemia in adriamycin-induced nephrotic rats

作　　者：武建文[1] 徐虹[1] 吴滢[1] 朱列伟[2] 陈莲[2] 

机构地区：[1]复旦大学附属儿科医院肾内科,上海200032 [2]复旦大学附属儿科医院病理科,上海200032

出　　处：《中华肾脏病杂志》2005年第4期207-212,共6页Chinese Journal of Nephrology

基　　金：国家自然科学基金(30070794)上海市科学技术委员会重点项目(034119809)

摘　　要：目的 动态观察血管形成素样蛋白3(angiopoietin-like protein 3,ANGPTL3)在阿 霉素大鼠肾病模型肾组织中表达水平的时相变化及细胞定位情况,探讨其与微小病变型肾病综 合征蛋白尿及高脂血症之间的关系。方法 给予大鼠一次性尾静脉注射阿霉素建立微小病变型 肾病综合征大鼠模型。采用免疫组织化学染色和斑点-ELISA,检测阿霉素注射后第7天、第14 天、第21天和第28天大鼠肾组织ANGFTL3的表达及分布。分析其与24 h尿蛋白量及血清胆 同醇(Cho)和甘油三酯(TG)的关系。结果(1)阿霉素注射后第14天开始出现大量蛋白尿(P<0.01), 血清白蛋白明显减少(P<0.01),Cho(P<0.01)和TG(P<0.05)明显增高,以上各项指标均在 第28天达高峰。(2)免疫组化定量分析显示阿霉素注射后第14天时,肾小球中ANGPTL3免疫 组化指数增高至同一时间点对照组的1.42倍(P<0.05);第21天时,为同一时间点对照组的 2.48倍(P<0.01),在肾小管中的表达也明显增高,免疫组化指数为同一时间点对照组的2.04 倍(P<0.01);到第28天,其在肾小球和肾小管中的表达均达最高水平,肾小球的免疫组化指 数为同一时间点对照组的3.28倍(P<0.01),肾小管的免疫组化指数为同一时间点对照组的 2.5倍(P<0.01)。(3)ANGPTL3在肾小球中的表达部位主要位于足细胞胞浆,此外,也可见于?Objective To observe the expression and distribution of angiopoietin-like protein 3(ANGPTL3) in kidney of adriamycin(ADR)-induced nephrotic rats, and to explore the possible association of ANGPTL3 with the development of proteinuria and hyperlipidemia. Methods Adriamycininduced nephrotic rat models were established by a single injection of adriamycin via the tail vein. Immunohistochemical staining (IHS)and dot-ELISA were used to examine the expression and distribution of ANGPTL3 in kidney and the level of ANGPTL3 in serum of ADR rats at day 7,14, 21 and 28 after adriamycin injection. Results (1) In ADR rats, urinary protein and the level of triglyceride and cholesterol in serum increased significantly at day 14 (P < 0.01, 0.05, 0.01, respectively), at the same time, serum albumin decreased significantly (P < 0.01)as compared to control.These indices reached the peak at day 28. (2)ANGPTL3 IHS index in glomeruli increased significantly by 42% and 148% of control at day 14 (P < 0.05) and day 21 (P < 0.01) respectively. As compared with control, ANGPTL3 IHS index increased significantly in renal tubuli at day 21 (P< 0.01). The peak level of ANGPTL3 expression in glomeruli and tubuli were both observed at day 28 (both P < 0.01). (3)The major site of ANGPTL3 expression in kidney was located in cytoplasm of podocytes as well as in tubular epithelial cells. (4)In ADR rats,serum ANGPTL3 level decreased significantly at day 7 compared to control (P< 0.01). No significant difference of serum ANGPTL3 level was found between ADR rat and control at day 14 and day 21 , while at day 28 ADR rats had a significantly higher ANGPTL3 level in serum than control (P < 0.05). (5) The ANGPTL3 expression in glomeruli was significantly correlated to the proteinuria level (r=0.81 ,P < 0.01). There was also significant correlativity between ANGPTL3 expression in renal tubuli and hyperlipidemia (Chor=0.70, P<0.01; TGr=0.65, P<0.01). Conclusions The expression of ANGPTL3 is presented in cytoplasm of podocytes of glomeruli and tubular epithelia

关 键 词：高脂血症 鼠肾组织 血管形成素 阿霉素肾病 微小病变型肾病综合征 斑点-ELISA 免疫组织化学染色 甘油三酯(TG) protein 免疫组化 肾小管上皮 尿蛋白量 细胞胞浆 蛋白表达水平 对照组 肾小球 尾静脉注射 血清胆固醇 血清白蛋白 

分 类 号：R692.9[医药卫生—泌尿科学]