摘要
目的探讨阿司匹林(ASA)预处理对大鼠局灶性脑缺血再灌注损伤的保护作用及其机制,并探讨其作用的最佳剂量。方法健康雄性SD大鼠60只随机分为假手术组,模型+溶媒组,ASA 10、50、150 mg/kg预处理组。以线栓法制作大鼠大脑中动脉缺血再灌注模型,于缺血2 h再灌注24 h后行5分制神经功能评分,并断头取脑分别测定脑梗死体积、凋亡细胞数及半胱胺酸蛋白酶蛋白3(caspase 3)和凋亡诱导因子(AIF)表达。结果与假手术组相比,模型+溶媒组脑梗死体积增大,凋亡细胞数增多,caspase 3和AIF表达增加(均P<0.01)。与模型+溶媒组相比,ASA 10、50、150 mg/kg预处理组脑梗死体积明显减小,神经功能不同程度改善,caspase3和AIF表达及凋亡细胞数减少(P<0.05,P<0.01)。ASA预处理组间比较,50 mg/kg组脑梗死体积、神经功能评分、凋亡细胞数以及caspase3和AIF表达降低最为显著,与10、150 mg/kg组比较差异均有统计学意义(P<0.05),而10 mg/kg与150 mg/kg组比较差异无统计学意义(P>0.05)。结论 ASA预处理对大鼠脑缺血再灌注损伤有一定保护作用,其作用机制与ASA抑制脑组织中caspase 3和AIF表达及抑制细胞凋亡有关;10、50、150 mg/kg 3种剂量中以50 mg/kg效果最佳。
Objective To explore neuroprotective effect of aspirin preconditioning on cerebral ischemia reperfusion injury in Sprague Dawley rats and its mechanism and the optimal dosage. Methods Sixty adult healthy male SD rats were randomly divided into sham-operated group, vehicle group, aspirin preconditioning groups respectively treated with 10 mg/kg, 50 mg/kg, 150 mg/kg. The middle cerebral artery occlusion/ reperfusion （MCAO/R） model was made by the suture method. After 24 h the animals were neurologically assessed on a 5 point scale, and then decapitated. The volume of infarction were measured by TTC staining,the expression of caspase3 and apoptosis inducing factor （ALE） were detected by immunohistochemistry, and the number of the apoptotic neurons was detected by TUNEL. Results Compared with sham group, the infarction volume enlarged, the expression of easepase 3, AIF and the number of nueronal apoptosis increased in vehicle group（P〈 0. 01 ）. Compared with vehicle group, the volume of infarction significantly reduced in aspirin preconditioning group （P〈0.05）, the neurological scores were improved （P〈0.05）, the expression of casepase 3, AIF and the number of neuronal apoptosis was significantly decreased （P 〈0.05）, 50 mg/kg aspirin preconditioning group had dramatically difference （ P 〈 0.01 ） ; compared with aspirin preconditioning groups respectively, 10 mg/kg and 150 mg/kg preconditioning groups had no statistical significance （P〉0. 05）, but other groups had statistical significance （P〈0.05）. Conclusions The results suggested that neuroprotective mechanism might be related to the decrease of casepase 3 and AIF protein expression and the number of TUNEL positive cells. The neuroprotective effect of 50 mg/kg groups was superior to 10 mg/kg and 150 mg/kg preconditioning groups.
出处
《中国神经免疫学和神经病学杂志》
CAS
2009年第4期281-284,288,共5页
Chinese Journal of Neuroimmunology and Neurology
基金
山西省回国留学人员科研基金资助项目(2008-59)
