Neuroprotective effectof Annexin A1 peptide Ac2-26 in rats after cardiopulmonary resuscitation
LUO Xin1, MAO Xinfa1, FAN Weibing1, LUO Xing1, SONG Yanju1, WU Weizhou2,3
1. Department of Neurology,the Third Hospital of Changsha,Changsha 410000,China; 2. Department of Neurology,the 985th Hospital of Joint Logistics Force,Taiyuan 030001,China; 3. Graduate Department,Logistics University of PAP,Tianjin 300309,China
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.
Sanganalmath S K, Gopal P, Parker J R, et al. Global cerebral ischemia due to circulatory arrest: insights into cellular pathophysiology and diagnostic modalities [J]. Mol Cell Biochem, 2017, 426(1-2): 111-127.
[2]
Qin C, Yang Y H, May L, et al. Cardioprotective potential of annexin-A1 mimetics in myocardial infarction [J]. Pharmacol Ther, 2015, 148: 47-65.
[3]
Vago J P, Tavares L P, Sugimoto M A, et al. Proresolving actions of synthetic and natural protease inhibitors are mediated by Annexin A1 [J]. J Immunol, 2016, 196(4): 1922-1932.
[4]
Senchenkova E Y, Ansari J, Becker F, et al. Novel role for the AnxA1-Fpr2/ALX signaling axis as a key regulator of platelet function to promote resolution of inflammation [J]. Circulation, 2019, 140(4): 319-335.
[5]
Zhang Z Q, Huang L, Zhao W, et al. Annexin 1 induced by anti-inflammatory drugs binds to NF-kappaB and inhibits its activation: anticancer effects in vitro and in vivo [J]. Cancer Res, 2010, 70(6): 2379-2388.
[6]
Gimenes A D, Andrade B F D, Pinotti J V P, et al. Annexin A1-derived peptide Ac2-26 in a pilocarpine-induced status epilepticus model: anti-inflammatory and neuroprotective effects [J]. J Neuroinflammation, 2019, 16(1): 32.
[7]
Trentin P G, Ferreira T P, Arantes A C, et al. Annexin A1 mimetic peptide controls the inflammatory and fibrotic effects of silica particles in mice [J]. Br J Pharmacol, 2015, 172(12): 3058-3071.
[8]
Yang H, Xu H G, Xiang Z, et al. Mitophagy in the hippocampus is excessive activated after cardiac arrest and cardiopulmonary resuscitation [J]. Neurochem Res, 2020, 45(2): 322-330.
[9]
Kida K, Ichinose F. Preventing ischemic brain injury after sudden cardiac arrest using NO inhalation [J]. Crit Care, 2014, 18(2): 212.
[10]
Kim E, Kim H C, Lee S, et al. Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats by inhibiting inflammation through inactivation of the TLR-4/NF-kappaB pathway [J]. Neurosci Lett, 2017, 649: 20-27.
Sugimoto M A, Vago J P, Teixeira M M, et al. Annexin A1 and the resolution of inflammation: modulation of neutrophil recruitment, apoptosis, and clearance [J]. J Immunol Res, 2016, 2016(8239258).
[13]
Mitchell J P, Carmodyr J. NF-kappaB and the transcriptional control of inflammation [J]. Int Rev Cell Mol Biol, 2018, 335: 41-84.
[14]
Zhang Z Q, Qing M, Shan B, et al. Neuroprotective effects of annexin a1 tripeptide after deep hypothermic circulatory arrest in rats [J]. Front Immunol, 2017, 8:1050.
[15]
Peshavariya H M, Taylor C J, Goh C, et al. Annexin peptide Ac2-26 suppresses TNFalpha-induced inflammatory responses via inhibition of Rac1-dependent NADPH oxidase in human endothelial cells [J]. PLoS One, 2013, 8(4): e60790.
2020, Vol. 31 
