Abstract: Objective To investigate the role ofprotectin D1 on cerebral ischemia reperfusion injury (CIRI) in mice.Methods Ninety C57BL/6 male mice were randomly divided into control group,model group and protectin D1 group.The CIRI model in mice was established by thread embolism method.The mice in the protectin D1 group were injected with 5 mg/kg protectin D1 through the tail vein 30 minutes before ischemia,and the mice in the control group and the model group were given the same amount of normal saline.After 24 hours of reperfusion,the infarct volume,brain water content and blood-brain barrier permeability of mice were measured.The neural function of mice was evaluated by Bederson scoring.The content of interleukin-1β (IL-1β),cyclooxygenase-2 (COX-2),tumor necrosis factor- α (TNF-α),superoxide dismutase (SOD),glutathione (CAT) and malondialdehyde (MDA) in the brain tissue of mice were detected.TUNEL staining was used to evaluate the apoptosis of brain tissue of mice.Results Compared with the control group,the volume of cerebral infarction,brain water content,blood brain barrier permeability,Bederson scoreand adhesion removal time in the model group were significantly increased,and the rotational drop time was significantly decreased (P＜0.05);Compared with the model group,the volume of cerebral infarction,brain water content,blood brain barrier permeability,Bederson score and adhesion removal time in the protectin D1 group were significantly decreased,and the rotational drop time was significantly decreased (P＜0.05).Compared with the control group,the level of IL-1β,COX-2 and TNF-α in the model group were increased significantly (P＜0.05);Compared with model group,the level of IL-1β,COX-2 and TNF-α were significantly decreased (P＜0.05).Compared with the control group,the contents of SOD and CAT in the model group were decreased significantly,while the content of MDA were increased (P＜0.05);Compared with the model group,the contents of SOD and CAT in the protectin D1 group were significantly increased,while the contents of MDA was significantly decreased (P＜0.05).Compared with the control group,the apoptosis index in the model group was increased significantly(P＜0.05);Compared with the model group,the apoptosis index in the protectin D1 group was significantly lower (P＜0.05).Conclusion Protectin D1 alleviates cerebral ischemia reperfusion injury in mice,and its mechanism is related to reducing inflammatory reaction,oxidative stress and apoptosis.

Key words: Protector D1, Cerebral ischemia reperfusion injury, Inflammation, Oxidative stress, Apoptosis

摘要： 目的 探讨保护素D1(protectin D1)对脑缺血再灌注损伤(cerebral ischemia reperfusion injury,CIRI)小鼠的保护作用及其机制研究。方法 90只C57BL/6雄性小鼠,随机分为对照组、模型组和保护素D1组。利用线栓法建立小鼠CIRI模型,保护素D1组小鼠在缺血前30 min,通过尾静脉注射5 mg/kg的保护素D1,假手术组和模型组小鼠则给予等量生理盐水。再灌注24 h后,测定各组小鼠的脑梗死体积、脑含水量和血脑屏障通透性。Bederson评分法、旋转实验和粘附去除实验评估各组小鼠的神经功能。检测各组小鼠脑组织白细胞介素-1β(IL-1β)、环氧合酶-2(COX-2)、肿瘤坏死因子-α(TNF-α)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)含量。TUNEL染色评估各组小鼠脑组织的凋亡情况。结果 与对照组比较,模型组小鼠脑梗死体积、脑含水量、血脑屏障通透性和Bederson评分和粘附去除时间显著升高,旋转掉落时间明显降低(P＜0.05);与模型组比较,保护素D1组小鼠脑梗死体积、脑含水量、血脑屏障通透性和Bederson评分和粘附去除时间显著降低,旋转掉落时间明显升高(P＜0.05)。与对照组比较,模型组小鼠脑组织IL-1β、COX-2和TNF-α水平显著升高(P＜0.05);与模型组比较,保护素D1组小鼠脑组织IL-1β、COX-2和TNF-α水平显著降低(P＜0.05)。与对照组相比,模型组小鼠脑组织SOD和CAT含量显著降低,MDA含量显著升高(P＜0.05);与模型组相比,保护素D1组小鼠脑组织SOD和CAT含量显著升高,MDA含量显著降低(P＜0.05)。与对照组相比,模型组小鼠脑组织凋亡指数明显升高;与模型组相比,保护素D1组小鼠脑组织凋亡指数明显降低(P＜0.05)。结论 保护素D1可减轻小鼠脑缺血再灌注损伤,其机制与降低炎症反应、氧化应激和细胞凋亡有关。

关键词: 保护素D1, 脑缺血再灌注损伤, 炎症反应, 氧化应激, 凋亡