罗格列酮对局灶性脑缺血再灌注大鼠的保护作用  

Protective effect of rosiglitazone reperfusion injury in rats

作　　者：谢晓燕[1,2,3] 徐勉[3] 朱榆红[4] 吉训明[2] 

机构地区：[1]济宁医学院第二附属医院内科,272051 [2]首都医科大学宣武医院脑血管病研究所, 北京100053 [3]昆明医学院第二附属医院内分泌与代谢病科,650101 [4]昆明医学院第二附属医院神经内科,650101

出　　处：《国际脑血管病杂志》2011年第3期214-219,共6页International Journal of Cerebrovascular Diseases

基　　金：云南省科技厅-昆明医学院联合专项基金（2007C0018R）

摘　　要：目的研究不同剂量罗格列酮（rosiglitazone，RSG）对局灶性脑缺血再灌注大鼠的保护作用。方法40只雄性Sprague—Dawley大鼠随机分为假手术组、对照组、小剂量RSG组[1mg／（1（g·d）]、中剂量RSG组[2mg／（kg·d）]和大剂量RSG组[4mg／（kg·d）]，每组8只。线栓法制备大鼠大脑中动脉闭塞2h再灌注22h模型。利用全自动生化分析仪测定血糖和血脂水平，采用固相夹心酶联免疫吸附法测定血清胰岛素水平，计算胰岛素敏感指数。观察罗格列酮对大鼠脑梗死体积和行为学的影响。结果与对照组比较，各RSG剂量组梗死体积显著缩小，神经功能评分显著改善（P〈0．05或P〈0．01），胰岛素敏感性显著增高（P〈0．05或P〈0．01），脑缺血后高血糖显著减轻（P〈0．05），呈剂量依赖性。结论RSG对脑缺血再灌注大鼠具有明显的神经保护作用，其机制可能与胰岛素敏感性提高有关。Objective To study the protective effect of different doses of rosiglitazone （RSG） against focal cerebral ischemia-reperfusion injury in rats. Methods Forty male Sprague Dawley rats were randomly divided into the following groups： sham-operation, control, low- dose RSG （1 mg/kg ·d）, moderate-dose （2 mg/kg · d）, high-dose （4 mg/kg· d） groups （n = 8 in each group）. A rat model of middle cerebral artery occlusion for 2 hours and reperfusion for 22 hours were induced by the intraluminal suture method. An automatic biochemical analyzer was used to detect the blood glucose and lipid levels. A solid phase sandwich enzyme-linked immunosorbent assay was used to determine serum insulin levels, and the insulin sensitivity indexes were calculated. The effect of rosiglitazone on infarct vohmae and behavioristics was observed. Results Compared with the control group, the infarct volume was significantly reduced, and the neurological function scores were improved significantly in each RSG gcoup （P 〈 0. 05 or P 〈 0.01）. The insulin sensitivity was sigtificantly increased （P 〈0. 05 or P 〈0. 01）, and hypergly- cemia was reduced significantly after cerebral ischemia （P 〈0.05） and showed a dose-dependent manner. Conclusions RSG has obvious neuroprotective effect against cerebral ischemia/ reperfusion injury in rats. Its mechanism may be associated with the increase of insulin sensitivity.

关 键 词：罗格列酮 噻唑烷二酮 脑缺血 再灌注损伤 胰岛素抗药性 高血糖症 神经保护药 大鼠 

分 类 号：R74[医药卫生—神经病学与精神病学] R9[医药卫生—临床医学]