罗格列酮对大鼠局灶性脑缺血葡萄糖再灌注性损伤的影响  

Effect of rosiglitazone on rat focal cerebral ischemia reperfusion injury induced by glucose

作　　者：谢晓燕[1] 于斌[2] 孙冰[1] 闫峰[3] 吉训明[3] 

机构地区：[1]济宁医学院第一临床学院内科学教研室,山东济宁272067 [2]济宁医学院第二临床学院中医教研室 [3]首都医科大学宣武医院北京市脑血管病转化医学重点实验室

出　　处：《中国老年学杂志》2017年第6期1316-1320,共5页Chinese Journal of Gerontology

基　　金：国家自然科学基金(No.81325007);济宁市科技发展计划项目(No.2008-25)

摘　　要：目的探讨血糖水平和胰岛素反应状态在局灶性脑缺血大鼠再灌注性脑损伤中的作用。方法将雄性SD大鼠随机分为局灶性脑缺血/再灌注模型生理盐水对照组、罗格列酮(RSG)高、中、低剂量预处理组(4、2、1 mg·kg^(-1)·d^(-1))、假手术组,每组8只。线栓法制备大鼠大脑中动脉闭塞2 h再灌注22 h模型(MCAO)。测定空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、血压、血清胰岛素水平,计算胰岛素敏感指数(IAI)。观察RSG对大鼠脑梗死体积和神经功能评分的影响。结果 IAI与梗死体积和神经功能评分存在相关性。与生理盐水对照组比较,RSG各剂量组脑梗死体积显著缩小,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),并呈剂量依赖性。结论高血糖和胰岛素抵抗共同作用加重局灶性脑缺血葡萄糖再灌注性脑损伤,且胰岛素抵抗更持久;RSG对脑缺血葡萄糖再灌注性脑损伤的神经保护,单纯降低血糖是不够的,改善胰岛素抵抗更重要。Objective To study the effect of blood glucose levels and insulin response state in rats with focal cerebral ischemia/ reperfusion（I/R） in brain injury. Methods Male SD rats were randomly divided into focal cerebral I/R models of physiological saline con- trol group （Control）, high, middle and low dose rosiglitazone （RSG） drug preconditioning （4,2,1 mg kg-1 d-1） and sham groups,8 rats in each group. All the rats except for those in the sham group were suffered from the middle cerebral artery embolism ischemia 2 h/reperfusion 22 h （MCAO）. Fasting plasma glucose （FPG）, blood lipid, serum insulin levels,insulin sensitivity index （IAI） were measured. The effect of RSG on the volume of cerebral infarction and the neurological deficits score of rats were observed. Results There was relation between IAI and infarct volume or neurological function score. RSG reduced infarct volume after ischemia and improved neurological function, at the same time it could increase insulin sensitivity, reduce high blood glucose after stroke in dose-dependent manner. Conclusions High glucose and insulin resistance could aggravate the focal cerebral I/R injury of brain, and insulin resistance is more durable. RSG has neuroprotective effects on cerebral I/R injury, simply reducing blood sugar is not enough, the improvement insulin resistance is more important.

关 键 词：罗格列酮 PPARΓ 葡萄糖再灌注损伤 胰岛素抵抗 高血糖 

分 类 号：R587.2[医药卫生—内分泌]