二十二碳六烯酸诱导细胞自噬减轻缺血性脑卒中神经损伤

发布时间：2018-04-09 16:55

  本文选题：二十二碳六烯酸　切入点：缺血性脑卒中　出处：《第三军医大学学报》2017年14期

【摘要】：目的探讨二十二碳六烯酸(docosahexaenoic acid,DHA)对大鼠缺血性脑卒中神经损伤的保护作用及其机制。方法利用60只280~330 g成年SD雄性大鼠建立永久性局灶脑梗死模型(permanent middle cerebral artery occlusion,pMCAO),按随机数字表法分为3组(n=20):假手术组、模型载体空白组(pMCAO+Veh)和模型DHA给药组(pMCAO+DHA)。建模成功后,按预设时间点对动物体质量、生存时间、神经功能、脑梗体积等大体指标进行评测;利用HE、Nissl染色对脑组织形态学改变进行观察;Western blot检测神经细胞自噬相关蛋白变化规律。结果造模后24、72 h,pMCAO+Veh组动物体质量及生存率较假手术组出现明显下降(P0.05),DHA给药可明显改善上述指标,但差异无统计学意义(P0.05);pMCAO+Veh组第7天生存率仅为38%,DHA早期干预可使第7天生存率提高至52%,但2组差异无统计学意义(P0.05),DHA可明显改善由疾病模型造成的神经功能,包括认知、感觉、运动功能,从而获得更高的神经功能分数及更少的平衡木错失(P0.05)。建模72 h后TTC染色发现,pMCAO+DHA组较pMCAO+Veh组可减少约17%的梗死体积(P0.05);HE及Nissl染色发现,DHA给药可显著减轻皮层梗死区神经细胞的病理性损伤;Western blot蛋白检测,DHA可显著抑制梗死后mTOR表达(P0.01),同时增强LC3Ⅰ/Ⅱ表达(P0.05)。结论 DHA可显著减轻由缺血性脑卒中引起的病理性改变,其保护机制可能为负性调控mTOR通路作用从而激活自噬。
[Abstract]:Objective to investigate the protective effect and mechanism of 22 carbohexaenoic acidoic acid on nerve injury in ischemic stroke rats.Methods A permanent focal cerebral infarction model was established in 60 adult male SD rats (280 ~ 330g). The permanent middle cerebral artery occlusion pMCAOG was divided into three groups according to random digital table: sham-operated group, model vector blank group (pMCAO Veh) and model DHA administration group (pMCAO DHAO).After modeling successfully, the gross indexes such as animal mass, survival time, nerve function and volume of cerebral infarction were evaluated according to preset time points.The changes of neuronal autophagy related proteins were detected by Western blot.Results the mass and survival rate of animals and animals in the pMCAO Veh group were significantly lower than those in the sham operation group.However, there was no significant difference between the two groups. The 7th day survival rate of the P0.05-pMCAO Veh group was only 38%. The early intervention of DHA could increase the survival rate from the 7th day to 52%, but there was no significant difference between the two groups. P0.05 Veh could significantly improve the neurological function caused by the disease model, including cognition and perception.Motor function, resulting in higher neurological function scores and less balance beam missed P0.05.After 72 hours of modeling, TTC staining showed that the infarct volume of pMCAO DHA group was about 17% less than that of pMCAO Veh group, and Nissl staining showed that it could significantly reduce the pathological injury of neurons in cortical infarct area.Postmortem mTOR expressed P0.01a and enhanced LC3 鈪，

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