阿托伐他汀对糖尿病大鼠内皮祖细胞及视网膜病变影响的研究  

Effects of atorvastatin on circulation endothelial progenitor cells and retinopathy in diabetic rats

作　　者：王筱梅[1] 刘少奎[1] 孟祥俊[1] 初楠[1] 杨桂美[1] 穆鑫[1] 洪军[1] 王翠荣[1] 

机构地区：[1]大连大学附属中山医院心内科,大连116001

出　　处：《中国循证心血管医学杂志》2009年第5期277-280,共4页Chinese Journal of Evidence-Based Cardiovascular Medicine

摘　　要：目的探讨他汀类药物对糖尿病大鼠循环内皮祖细胞(EPCs)及视网膜病变的影响及作用机制。方法成年Wistar大鼠150只,随机分为2组。正常对照组(阴性组),糖尿病组(阳性组)。注射链尿佐菌素(STZ),造糖尿病大鼠模型。将糖尿病大鼠再随机分为3组:低剂量组(他汀10mg/Kg.d),高剂量组(他汀20 mg/Kg.d),单纯糖尿病组。灌胃给药,对照组及单纯糖尿病组给予等量生理盐水。大鼠分别于3个月,6个月时按比例随机处死。取动脉血检测EPCs数量、取眼球固定后观察视网膜血管内皮生长因子(VEGF)蛋白表达情况。结果糖尿病大鼠造模成功率81%。3个月及6个月时,低剂量组存活率均较高剂量组及单纯糖尿病组有所增加(P<0.05)。他汀类药物促进EPCs数量上升,低剂量组与对照组、糖尿病组、高剂量组比较,3个月及6个月时各组间均有统计学意义(P>0.05),高剂量组与对照组及糖尿病组比较无统计学差异(P<0.05)。不同剂量的他汀类药物对视网膜VEGF蛋白表达情况:糖尿病组VEGF免疫阳性表达最强,高剂量组VEGF免疫阳性表达比糖尿病组减弱,低剂量治疗组VEGF免疫阳性表达最低。结论他汀类药物能够促进EPCs数量增加。小剂量他汀类药物可抑制糖尿病大鼠视网膜VEGF表达,减缓视网膜病变进展;并降低糖尿病大鼠的死亡率。Objective To investigate the effects of statins on circulation endothelial progenitor cells （EPCs） and retinopathy in diabetic rats and the mechanism. Methods Adult Wistar rats （ n = 150 ） were randomly divided into the normal control group （ negative group） and diabetes group （ positive group ）. The rat model of diabetes was established by the injection of streptozoein （ STZ ）. The diabetic rats were then randomly divided into 3 groups including the low-dose group （ atorvastatin, 10 mg/kg/d） , high-dose group （ atorvastatin ,20 mg/kg/d） and diabetes group. Atorvastatin was given orally to the low-dose group and high-dose group respectively, and the control group and diabetes group was given equivalent normal saline solution. After 3 and 6 months the rats were killed randomly in proportion and arterial blood was collected to detect EPCs quantity, and the protein expression of retina vascular endothelial growth factor （ VEGF ） was observed after the eyeball fixation. Results The success rate of diabetic rat modeling was 81%. The survival rate of EPCs was higher in the low-dose group than that in the high-dose group and diabetes group （ P 〈 0.05 ） at 3 months and 6 months respectively. The quantity of EPC was increased by statins, and the comparison between the low-dose group and the normal control group, diabetes group or high - dose group showed a statistical significance at 3 months and 6 months respectively （ P 〉 0.05 ）. The comparison between high-dose group and the normal control group or diabetes group showed no statistical difference （ P 〈 0.05 ）. The effects of statins in different doses on the protein expression of retina VEGF showed as follows ： in the diabetes group the immune positive expression of VEGF was the highest, but decreased in the high-dose group, and the lowest in the lowdose group. Conclusion Statins can improve the increase of EPCs quantity, and in low dose, it can inhibit the expression of retina VEGF, delay the development of retinopath

关 键 词：阿托伐他汀 糖尿病视网膜病变 循环内皮祖细胞 血管内皮生长因子 大鼠 

分 类 号：R587.1[医药卫生—内分泌]