利拉鲁肽对急性脑缺血再灌注大鼠的干预效果

Intervention effect of liraglutide on rats with acute cerebral ischemia-reperfusion

目的分析胰高血糖素样肽-1类似物利拉鲁肽对急性脑缺血再灌注大鼠的影响,探讨利拉鲁肽对急性脑缺血再灌注大鼠干预的可能机制,为临床胰高血糖素样肽-1受体激动剂用于缺血性卒中提供理论依据。方法成年雄性清洁级SD大鼠60只,体质量280~300 g,采用随机数字表法分成假手术组、模型组、不同剂量利拉鲁肽(160、120、80μg/kg)组,每组12只。采用Longa线栓法制备大鼠大脑中动脉闭塞2 h/再灌注24 h模型。利拉鲁肽各剂量组于缺血前2 h和再灌注0、12 h腹腔注射利拉鲁肽160、120、80μg/kg,假手术组和模型组腹腔注射等体积生理盐水,24 h后处死。参考Longa评分对各组大鼠的神经功能缺损情况进行评分,大鼠处死后迅速取脑组织,计算脑梗死体积,测定脑组织中丙二醛(malondialdehyde,MDA)、谷氨酸(glutamic acid,Glu)含量和超氧化物歧化酶(superoxide dismutase,SOD)活性。结果假手术组Longa评分为0分,无神经功能损伤症状;与模型组比较,利拉鲁肽各剂量组神经功能缺损评分均明显降低,差异均有统计学意义(P<0.05)。模型组和利拉鲁肽各剂量组经再灌注24 h后可见梗死灶及脑组织肿胀;利拉鲁肽各剂量组脑梗死体积均较模型组明显减小,差异均有统计学意义(P<0.05);且利拉鲁肽各剂量组之间比较,差异亦有统计学意义(P<0.05)。与假手术组比较,模型组大鼠脑组织中MDA、Glu含量显著增高,SOD活性显著降低,差异均有统计学意义(P<0.05);与模型组比较,利拉鲁肽各剂量组脑组织中MDA、Glu含量均显著降低,SOD活性显著升高,差异均有统计学意义(P<0.05),且利拉鲁肽各剂量组之间比较,差异均有统计学意义(P<0.05)。结论胰高血糖素样肽-1类似物利拉鲁肽对急性脑缺血再灌注大鼠神经损伤具有保护作用,降低氧化应激反应。

Objective To observe the effect of the glucagon-like peptide 1(GLP-1)analogue,liraglutide,in rats with acute cerebral ischemia-reperfusion,and to explore its possible mechanism,to provide a theoretical basis for ischemic stroke.Methods Sixty adult male Sprague-Dawley rats,clean grade,weighing about 280-300 g,were divided randomly into five groups(n=12 each):a sham-operation group,model group,and different dose of liraglutide groups.A middle cerebral artery occlusion model was established by the Longa suture method.Rats in the liraglutide groups were injected intraperitoneally with liraglutide 160,120,or 80μg/kg,respectively,at 2 h before ischemia and 0 and 12 h after reperfusion.Rats in the shamoperation and model groups were injected intraperitoneally with the same volume of normal saline,and killed24 h later.Neurological deficitsin each group were scored according to the Longa score.The rats were killed and the brain tissues were removed rapidly.The cerebral infarction volume was calculated,and the malondialdehyde(MDA)and glutamic acid(Glu)contents,and superoxide dismutase(SOD)activity in the brain tissue were measured.Results The Longa score in the sham-operation group was 0,indicating no neurological impairment.The Longa scores were significantly lower in the liraglutide groups compared with the model group(P<0.05).Infarction and brain tissue swelling were seen 24 h after reperfusion in the model and liraglutide groups.The cerebral infarction volume was significantly smaller in the liraglutide groups compared with the model group(P<0.05),with a significant dose-dependent effect(P<0.05).The MDA and Glu brain levels were significantly higher and SOD activity was significantly lower in the model group compared with the sham-operation group(P<0.05),while MDA and Glu levels were significantly lower and SOD activity was significantly higher in the liraglutide groups compared with the model group,with a significant dose-dependent effect(all P<0.05).Conclusion The GLP-1 analogue liraglutide has a protective effect against acute cerebral ischemia-reperfusion injury and reduces oxidative stress in rats.