1-磷酸鞘氨醇受体2在大鼠心脏停搏复苏后脑损伤中的作用

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目的:评价1-磷酸鞘氨醇受体2(S1PR2)在大鼠心脏停搏复苏后脑损伤中的作用。方法:清洁级健康雄性SD大鼠45只,体重280~320 g,8~10周龄,采用随机数字表法分为3组(n n=15):假手术组(S组)、心脏停搏复苏组(CAR组)和S1PR2拮抗剂JTE013组(JTE组)。采用经食道心脏起搏法建立大鼠心脏停搏模型,并进行心肺复苏。复苏即刻,JTE013组腹腔注射10 mg/ml JTE-013 1 ml;S组和CAR组腹腔注射等容量DMSO。分别于复苏后24和48 h时采用条带移除实验评价神经功能;于复苏后48 h时处死大鼠,检测脑含水量和血脑屏障通透性,采用Western blot法检测皮层组织S1PR2和occludin的表达水平,明胶酶谱法检测皮层组织基质金属蛋白酶-9(MMP-9)的活性,电镜下观察血脑屏障超微结构。n 结果:与S组比较,CAR组和JTE组复苏后24和48 h时条带移除时间延长,脑含水量和血脑屏障通透性增加,皮层组织S1PR2表达上调,MMP-9活性升高,occludin表达下调(n P<0.05);与CAR组比较,JTE组复苏后48 h时条带移除时间缩短,脑含水量和血脑屏障通透性降低,皮层组织S1PR2表达下调,MMP-9活性降低,occludin表达上调(n P<0.05)。n 结论:S1PR2参与了大鼠心脏停搏复苏后脑损伤过程。“,”Objective:To evaluate the role of sphingosine 1-phosphate receptor 2 (S1PR2) in brain injury after cardiac arrest and resuscitation in rats.Methods:Forty-five clean-grade healthy male Sprague-Dawley rats, weighing 280-320 g, aged 8-10 weeks, were divided into 3 groups (n n=15 each) using a random number table method: sham operation group (group S), cardiac arrest resuscitation group (group CAR), and S1PR2 antagonist JTE013 group (group JTE). Cardiac arrest was induced by transoesophageal cardiac pacing, and cardiopulmonary resuscitation was performed.Immediately after resuscitation, 10 mg/ml JTE013 1 ml was intraperitoneally injected in JTE013 group, and the equal volume of DMSO was intraperitoneally injected instead in S group and CAR group.The nerve function was evaluated by tape removal test at 24 and 48 h after resuscitation.Rats were sacrificed at 48 h after resuscitation, the brain water content and blood-brain barrier permeability were measured, the expression of S1PR2 and occludin in the cortical tissue was detected by Western blot, the activity of matrix metalloproteinase-9 (MMP-9) was detected by gelatin zymography method, and the ultrastructure of blood-brain barrier was observed with an electron microscope.n Results:Compared with group S, the time to removal of the tape was significantly prolonged at 24 and 48 h after resuscitation, the brain water content and permeability of blood brain barrier were increased, the expression of S1PR2 in cortical tissues was up-regulated, the activity of MMP-9 was increased, and the expression of occludin was down-regulated in CAR and JTE groups (n P<0.05). Compared with group CAR, the time to removal of the tape was significantly shortened at 48 h after resuscitation, the brain water content and permeability of blood brain barrier were decreased, the expression of S1PR2 in cortical tissues was down-regulated, the activity of MMP-9 was decreased, and the expression of occludin was up-regulated in group JTE (n P<0.05).n Conclusion:S1PR2 is involved in the brain injury after cardiac arrest and resuscitation in rats.
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