辛伐他汀对大鼠高血糖状态缺血后血管新生的影响作用  

Effect of simvastatin on postischemic angiogenesis in hyperglycemic diabetic rats

作　　者：陶蕊[1] 段俊丽[1] 倪培华[2] 潘志红[1] 刘蓓菁[1] 郑楠[3] 

机构地区：[1]上海交通大学医学院附属新华医院老年科,上海200092 [2]上海交通大学医学院附属瑞金医院检验系,上海200025 [3]上海交通大学医学院附属新华医院生物发育学研究中心,上海200092

出　　处：《诊断学理论与实践》2008年第3期318-322,共5页Journal of Diagnostics Concepts & Practice

基　　金：上海市卫生局基金(编号054057);红外物理国家重点实验室开放性课题

摘　　要：目的:探讨辛伐他汀(SV)对链脲佐菌素(STZ)诱导高血糖状态下,单侧下肢血管结扎缺血后的大鼠血管新生情况。方法:将36只雄性SD大鼠随机分为3组(每组12只),正常对照组(NC组)、糖尿病组(DM组)及SV治疗组(DM+SV组)。用STZ诱导制作DM大鼠模型后,行手术结扎并切除其左侧股动、静脉,造成单侧下肢缺血,DM+ SV组每日予SV 10 mg/kg连续灌胃14 d。于第0、7天检测尾静脉血糖(GLU);第15天处死大鼠,并检测血清GLU、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、总抗氧化能力(TAOC)、黄嘌呤氧化酶(XOD)和肌肉组织中超氧化物歧化酶(SOD)、丙二醛(MDA)、一氧化氮(NO)和环磷酸鸟苷(cGMP)含量:采用碱性磷酸酶(AKP)染色法测定缺血区域肌肉毛细血管密度,应用钡剂造影后观察其双下肢血管情况。结果:大鼠术后第15天,其毛细血管评分计数和毛细血管密度检测表明,DM组(5.46±1.12、58.70±3.63)低于NC组(18.60±2.73、71.55±15.50),而DM+SV组(12.00±1.63、63.79±6.94)则较DM组明显升高(P均<0.05)。结论:STZ诱导的高血糖状态,对大鼠缺血后新生血管生成有明显抑制作用;而SV可恢复其高血糖状态下受抑制的血管新生。Objective To study the effect of simvastatin on angiogenesis after unilateral hindlimb vessel ligation induced ischema in hyperglycemic diabetic rats induced by injection of streptozotocin. Methods Thirty six SD rats were randomly divided into three group （12 rats for each group）：normal control （NC）, diabetes （DM）, and simvastatin-treated （DM＋SV） groups. After the establishment of diabetes by injection of streptozotocin, unilateral hindlimb ischemia was induced by ligation and excision of left femoral artery and vein; rats in DM＋SV group were given simvastatin （SV） 10 mg/kg by gastric infusion for 14 days. Blood glucose level via caudal vein was determined on 0 and 7th days. Rats were sacrificed on 15th day and blood glucose （GLU）, total cholesterol （TC）, triglycerol （TG）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C）, total antioxidation capacity （TAOC）, xanthine oxidase （XOD） and muscle contents of superoxide dismutase （SOD）, malondialdehyde （MDA）, nitrous oxide （NO）, cyclic guanosine monophosphate （cGMP） were determined. Density of capillaries in muscles of ischemia region was determined by alkaline phosphatase stain method and vessel status of lower limb was observed by barium contrast. Results Fifteen days after operation, capillary, score and capillary density were significantly lower in DM group （5.46±1.12, 58.70±3.63） than that in control group （18.60±2.73, 71.55±15.50, P〈0.05）. However, capillary score and capillary density were significantly restored in DM＋SV group （12.00±1.6, 63.79±6.94, P〈0.05）. Conclusions The hyperglycemic status induced by streptozotocin had significant inhibitory effect on neovessel angiogenesis in response to hindlimb ischemia and this could be reversed by the administration of simvastatin.

关 键 词：他汀 糖尿病 缺血 血管新生 

分 类 号：R364.4[医药卫生—病理学]