缺氧诱导因子1α对糖尿病大鼠中性粒细胞CD18表达和视网膜白细胞黏附的影响  

Influence of hypoxia-inducible factor-1α on the expression of neutrophil CD18 and leukocyte adhesion in diabetic rats

作　　者：宋虎平[1] 惠延年[2] 王丽丽[1] 

机构地区：[1]西安市第四医院眼科,710004 [2]第四军医大学西京医院眼科

出　　处：《中华眼底病杂志》2008年第4期268-271,共4页Chinese Journal of Ocular Fundus Diseases

基　　金：陕西省科技发展计划项目（2005K14-F6）

摘　　要：目的 观察缺氧诱导因子1α（HIF-1α）对早期糖尿病视网膜病变（DR）大鼠外周血中性粒细胞 表面CD18表达以及视网膜白细胞和血管内皮细胞黏附的影响。方法 雄性Sprague-Dawley大鼠，链脲佐菌素腹腔注射诱导糖尿病模型。2个月后，取18只糖尿病模型大鼠随机分为糖尿病组（B组）、糖尿病＋HIF-1α反义寡核苷酸组（ASODN）（C组）、糖尿病＋HIF-1α正义寡核苷酸组（SODN）（D组），每组各为6只大鼠。年龄匹配的正常大鼠6只作为正常对照组（A组）。A、B组注射等量5%葡萄糖溶液，C、D组分别通过鼠尾静脉注射ASODN和SODN（025mg/kg）。分别以流式细胞仪和丫啶橙白细胞造影观察外周血中性粒细胞CD18水平及视网膜白细胞黏附量。结果 外周血中性粒细胞CD18的阳性细胞比例，B组为（44.93±3.60）%， A组为（18.66±1.52）%，C组为（31.66±4.72）%，D组为（51.00±5.66）%；各组之间比较，差异有统计学意义（F=42.46, P〈0.001）。丫啶橙视网膜白细胞染色阳性细胞数，A组为（46.16±10.68）个，B组为（133.83±20.43）个，C组为（99.83±9.28）个，D组为（121.33±10.23）个。B组阳性染色细胞数较A组提高约2.89倍；C、D组与B组比较，差异无统计学意义（P=0.12，95%可信区间为-3.69～28.69）。结论 在体内实验条件下，HIF-1α蛋白能够下调糖尿病动物外周血中性粒细胞表达CD18及视网膜白细胞聚集。HIF-1α有可能成为早期DR药物治疗的靶点。Objective To observe the influence of the expression of CD18 on the neutrophile and the leukocyte adhesion to retinal vascular endothelium by hypoxia-inducible factor-1 alpha （HIF-1α） in early diabetic retinopathy rats. Methods Male Sprague-Dawley rats received intraperitoneal injection of streptozotocin to induce diabetes model. 18 diabetic rats were divided into 3 groups randomly after 2 months of diabetes induction, including diabetic group （group B）, HIF-1α anti-sense oligonucleotides （ASODN） injection group （group C） and HIF-1α sense oligonucleotides （SODN） injection group （group D）, the age and weigh matched health rats were chosen as control group （group A）, with 6 rats in each group. Then group A and B rats received 5% glucose solution caudalis veins injection, group C and group D rats received HIF-1α ASODN and HIF-1α SODN caudalis veins injection, respectively（025 mg/kg）.The level of CD18 on the neutrophil isolated from the peripheral blood was measured by flow cytometry. Retinal leukostasis was quantified with acridine orange leukocyte fluorography. Results The percentage of CD18 positive neutrophil cell was（44.93±3.60）% in group B,（18.66±1.52）% in group A,（31.66±4.72）% in group C,（51.00±5.66）% in group D. Compared with each other groups,the differences are statistically significant （F=42.46, P〈0.001）. The number of positive staining cells of retinal leukocyte was （46.16±10.68）in group A,（133.83±20.43）in group B,（99.83±9.28）in group C,（121.33±10.23） in group C. Compared group B with group C,the number of positive staining cells raised about 2.89 times;compared group B with group C and D,the differences are statistically significant （P=0.12,95% confidence interval -3.69～28.69）.Conclusions In vivo, HIF-1α can decreased the expression of CD18 on neutrophils from diabetic rats′ peripheral blood and the collection of retinal leukostasis in the diabetic animals. HIF-1α may serve as a therapeutic target for the trea

关 键 词：糖尿病视网膜病变/病理生理学 缺氧诱导因子1 Α亚基 抗原 CD18 中性白细胞/生理学 糖尿病 实验性 

分 类 号：R774.1[医药卫生—眼科]