膜联蛋白A1拟肽Ac2-26对大鼠心肺复苏后脑神经损伤的保护作用

Neuroprotective effectof Annexin A1 peptide Ac2-26 in rats after cardiopulmonary resuscitation

目的研究膜联蛋白A1拟肽Ac2-26在大鼠心肺复苏后对脑损伤神经的保护作用。方法随机将45只模型大鼠分为假手术组、对照组、Ac2-26组,每组15只。假手术组行动静脉穿刺和气管插管;对照组、Ac2-26组行5 min窒息处理,在自主循环恢复后分别从静脉给予生理盐水、Ac2-26(1 mg/kg)。评估三组大鼠术后3 d的存活率,评估术前及术后24、48、72 h神经功能缺损评分;采用ELISA法检测术后3 d大鼠血清中IL-1β、IL-6、TNF-α浓度;采用Western Blot检测大鼠前额叶皮层和海马中NF-κB蛋白的表达水平。结果术后3 d假手术组大鼠生存率为100%,对照组为53.3%,Ac2-26组为73.3%,与对照组比较,Ac2-26组大鼠在心肺复苏后3 d的累计生存率明显升高。与假手术组相比,对照组各时间点神经功能缺损评分均降低(P<0.01),而Ac2-26组均高于对照组(P<0.01)。Ac2-26组术后3 d血清中IL-1β、IL-6、TNF-α水平较对照组降低,差异有统计学意义(P<0.05),而与假手术组相比,Ac2-26组血清中IL-1β、IL-6、TNF-α水平略升高。Ac2-26组大鼠前额叶皮层和海马中NF-κB蛋白相对表达水平较对照组降低,差异有统计学意义(P<0.05),而Ac2-26组与假手术组皮层和海马中NF-κB蛋白表达水平[(0.174±0.039)vs(0.177±0.054),(0.298±0.014)vs(0.272±0.022)]相比,差异无统计学意义。结论膜联蛋白A1拟肽Ac2-26对大鼠心肺复苏后脑损伤具有神经保护作用。

Objective To explore the protective effect of Annexin A1 peptide Ac2-26 on brain injury after cardiopulmonary resuscitation in rats.Methods Forty-five rats were randomly divided into the sham group,control group and Ac2-26 group,with 15 in each.The sham group underwent only conducted tracheal intubation and arteriovenous puncture while the control group and Ac2-26 group were subjected to five-minute asphyxia.After the recovery of spontaneous circulation,rats in the Ac2-26 group were intravenously injected with Ac2-26(1 mg/kg),but an equal amount of saline was infused in the control group.The rats were evaluated preoperatively and at 24 h,48 h and 72 h after spontaneous circulation recovery according to the neurological deficit score.The ELISA method was used to determine the concentrations of IL-1β,IL-6 and TNF-αin the serum of each group at 72 h.After three days of spontaneous circulation recovery,the rat cortex and hippocampus were taken to measure the expression of NF-κB in each group by Western Blot.Results The survival rate was 100%in the sham group,53.3%in the control group and 73.3%in the Ac2-26 group three days after operation.Compared with the control group,the cumulative survival rate of the Ac2-26 group was significantly increased three days after cardiopulmonary resuscitation.Compared with the sham operation group,the scores of neural function defects in the control group decreased at each time point(P<0.01).However,compared with the control group,the neurological impairment score in the Ac2-26 group increased at each time point(P<0.01).The serum levels of IL-1β[(35.9±6.2)pg/ml],IL-6[(32.9±5.7)pg/ml]and TNF-α[(25.5±3.5)pg/ml]in the Ac2-26 group three days after operation were significantly lower than those in the control group[(82.5±10.2)pg/ml,(64.5±9.3)pg/ml,(39.9±7.6)pg/ml](P<0.05).The expression level of NF-κB protein in the prefrontal cortex and hippocampus of rats in the Ac2-26 group[(0.174±0.039),(0.298±0.014)]was significantly lower than that of the control group[(0.393±0.056),(0.450±0.027)](P<0.05).There was no significant difference in the expression level of NF-κB protein between the Ac2-26 group and the sham group[(0.174±0.039)vs(0.177±0.054),(0.298±0.014)vs(0.272±0.022)].Conclusions Annexin A1 peptide Ac2-26 has neuroprotective effects on brain injury after cardiopulmonary resuscitation in rats.