二十碳五烯酸对急性脑梗死大鼠梗死体积、神经功能及氧化应激-炎症反应的影响

Effects of eicosapentaenoic acid on the infarction volume,neurofunction and oxidative stress-inflammation response in acute cerebral infarction rats

目的:探讨二十碳五烯酸(EPA)对急性脑梗死大鼠梗死体积、神经功能及氧化应激-炎症反应的影响。方法:采用大脑中动脉线栓法建立急性脑梗死大鼠模型。将48只模型大鼠随机分为模型组及低、中、高剂量(150、300、600 mg/kg)EPA组,每组12只,每天给药1次,连续给药14 d;另设假手术组(n=12)。采用mNSS评分法评价造模后第1、3、7、14天大鼠神经功能缺损情况,采用TCC染色测量第1、14天脑梗死体积,采用ELISA法检测第14天大鼠脑组织中氧化应激因子超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)和炎症因子超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)表达情况,Western blot法检测大鼠脑组织中血管内皮生长因子(VEGF)蛋白表达水平。结果:与假手术组相比,模型组大鼠第3、7、14天的mNSS评分增高(P<0.05);低、中、高剂量EPA组第7、14天mNSS评分均低于模型组(P<0.05)。假手术组未见脑组织梗死区域;模型组大鼠第14天的脑梗死体积增大,而与模型组比较,低、中、高剂量EPA组脑梗死体积缩小(P<0.05),且呈现一定的剂量依赖性。第14天,与假手术组相比,模型组大鼠脑组织中SOD、CAT水平降低,MDA、hs-CRP、TNF-α及IL-6水平升高;与模型组相比,中、高剂量EPA组SOD、CAT水平升高,MDA、hs-CRP、TNF-α及IL-6水平降低(P<0.05)。与假手术组相比,模型组大鼠脑组织中VEGF蛋白表达水平降低;与模型组相比,低、中、高剂量EPA组VEGF蛋白表达水平升高(P<0.05),呈现出一定的剂量依赖性。结论:EPA可降低急性脑梗死大鼠的脑梗死体积,改善神经功能,有效缓解氧化应激-炎症反应,其作用机制可能与促进脑血管新生有关。

Aim:To investigate the effects of eicosapentaenoic acid(EPA)on the infarction volume,neurofunction and oxidative stress-inflammation response in acute cerebral infarction(AMI)rats.Methods:Sixty rats were assigned to sham operation group,model group,and low-,middle-,high-dose EPA groups(n=12).The rats in the latter 4 groups were made AMI model by middle cerebral artery occlusion,and rats in the latter 3 groups were treated with 150,300 and 600 mg/kg EPA once a day for 14 days.The mNSS was used to evaluate the impairment of neurofunction on the 3rd,7th,and 14th day.The volume of cerebral infarction on the 1st and 14th day was detected by TTC staining.The levels of oxidative stress-inflammation response factors such as SOD,CAT,MDA and hs-CRP,TNF-α,IL-6 in brain tissue were detected by ELISA.The expression of VEGF in brain tissue was assessed by Western blot.Results:Compared with sham operation group,the mNSS score was higher in the model group on the 1st,3rd,7th,and 14th day(P<0.05);compared with model group,the mNSS score in the low-,middle-,high-dose EPA groups was lower on the 7th and 14th day(P<0.05).There was no infarction area in the sham operation group.On the 14th day,the volume of cerebral infarction in the model group increased,while compared with the model group,the volume of cerebral infarction in the low-,middle-,high-dose EPA groups decreased in a certain dose-dependent manner(P<0.05).Compared with the sham operation group,the levels of SOD and CAT in the model group decreased,the levels of MDA,hs-CRP,TNF-α,and IL-6 increased,and that of VEGF decreased;compared with the model group,the above parameters all improved in the middle-and high-dose EPA groups(P<0.05).Conclusion:EPA could effectively reduce the volume of cerebral infarction,improve the neurofunction and reduce the oxidative stress-inflammation response,which may be involved in the cerebral neovascularization.