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。
Abstract
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-α in 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.
关键词
膜联蛋白A1 /
Ac2-26 /
心肺复苏 /
自主循环恢复
Key words
ANXA1 /
Ac2-26 /
cardiopulmonary resuscitation /
spontaneous circulation recovery
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