摘要
目的探讨阿司匹林(ASA)预处理对大鼠脑缺血再灌注损伤的神经保护作用机制。方法将健康成年雄性SD大鼠随机分为假手术组、脑缺血再灌注模型组(模型组)及ASA预处理大、中、小剂量组。模型组及ASA预处理组以线栓法建立大鼠右侧大脑中动脉缺血再灌注模型,ASA预处理大、中、小剂量组分别于造模前按体质量150mg/(kg.d)、50mg/(kg.d)和10mg/(kg.d)予ASA水溶片混悬液灌胃,连续5d;其他两组予等体积生理盐水连续灌胃。每组12只进入实验。采用Longa评分法进行神经功能评分,TTC染色测量脑梗死体积,放射免疫法检测脑组织肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)水平。结果模型组与ASA预处理组均可见大脑中动脉供血区梗死灶,ASA预处理大、中、小剂量组梗死灶〔(97.247±2.146)%、(94.141±0.996)%,93.507±2.262)%〕均较模型组〔(99.483±1.303)%〕缩小(P<0.05);ASA预处理中、小剂量组脑组织神经功能评分(分别为1.67±0.651、1.50±0.674)较模型组(2.33±0.492)降低(P<0.05、P<0.01);ASA预处理中、小剂量组脑组织TNF-α水平〔分别为(4.378±0.205)ng/mL、(4.318±0.146)ng/mL〕较模型组〔(4.843±0.419)ng/mL〕降低(P<0.01),IL-6水平〔分别为(364.56±12.37)ng/mL、(372.67±24.48)ng/mL〕较模型组〔(340.32±10.65)ng/mL〕升高(P<0.05);与ASA预处理中、小剂量组比较,ASA预处理大剂量组TNF-α水平〔(4.695±0.225)ng/mL〕增高(P<0.05),IL-6水平〔(345.74±12.42)ng/mL〕降低(P<0.05)。ASA预处理大剂量组神经功能评分、脑组织TNF-α、IL-6水平与模型组比较差异无统计学意义(P>0.05)。结论 ASA预处理可通过抑制脑缺血再灌注损伤过程中的炎性反应而发挥神经保护作用,其机制可能与抑制TNF-α和升高IL-6水平有关。
Objective To explore the neuroprotective mechanisms and effective dose of aspirin（ASA） preconditioning in brain damage following cerebral ischemic reperfusion in rats.Methods Sixty healthy male SD rats were randomly divided into five groups： the sham-operated group,the model group,and preconditioning groups treated with three different doses of aspirin（10 mg/kg,50 mg/kg,and 150 mg/kg,respectively）.12 rats were included in each group.The middle cerebral artery occlusion reperfusion（MCAOR）model was established by the suture method in the model group and the three aspirin preconditioning groups.Before making the MCAOR model,the rats in the aspirin preconditioning groups were lavaged with soluble aspirin tablets once a day at the doses of 10 mg/kg,50 mg/kg and 150 mg/kg,respectively,for 5 consecutive days,and the same volume of normal saline was lavaged for 5 consecutive days in the sham operation group and model group.The infarction volume was revealed by TTC stain and the neurological function was scored with Longa 5-point scale.The contents of TNF-α and IL-6 were detected by RIA method.Results Compared with the model group [（99.483±1.303） %],the infarction volume was smaller in the low dose,the middle dose and the high dose ASA preconditioning groups [（93.507±2.262）%,（94.141±0.996）% and（97.247±2.146）%]（P〈0.05）.Compared with the model group（2.33±0.492）,the improved neurological outcome scores decreased in the low dose and middle dose ASA preconditioning groups [（1.50±0.674）,（1.67±0.651）]（P〈0.05,P〈0.01）.Compared with the model group,the content of TNF-α（4.318±0.146 ng/mL,4.378±0.205 ng/mL） was significantly decreased（P〈0.01） and the content of IL-6（372.67±24.48 ng/mL,364.56±12.37 ng/mL） was increased（P〈0.05） in the low dose and middle dose ASA preconditioning groups.Compared with the high dose of ASA preconditioning group,TNF-α level was decreased and IL-6 levels was increased in the low dose and middle dose ASA preconditioning groups（P〈0.05）.However,there was no significant different in the contents of TNF-α and IL-6 between the high dose ASA preconditioning group and the model group（P〉0.05）.Conclusions ASA preconditioning could have potential protective effects in brain ischemic reperfusion injury.This could be achieved by inhibiting the inflammatory response and the mechanism could be TNF-α inhibition and IL-6 elevation.
出处
《中国神经免疫学和神经病学杂志》
CAS
北大核心
2012年第5期358-361,共4页
Chinese Journal of Neuroimmunology and Neurology
基金
山西省回国留学人员科研资助项目(200859)
