Background/Aims: This study was to examine the role played by hypoxia inducible factor-1 (HIF-1 alpha) in regulating pro-inflammatory cytokines (PICs) pathway in the rat hippocampus after cardiac arrest (CA) induced-transient global ischemia followed by cardiopulmonary resuscitation (CPR). Those PICs include interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). Methods: A rat model of CA induced by asphyxia was used in the current study. Following CPR, the hippocampus CA1 region was obtained for ELISA to determine the levels of HIF-1 alpha and PICs; and Western Blot analysis to determine the protein levels of PIC receptors. Results: Our data show that IL-1 beta, IL-6 and TNF-alpha were significant elevated in the hippocampus after CPR as compared with control group. This was companied with increasing of HIF-1 alpha and the time courses for HIF-1 alpha and PICs were similar. In addition, PIC receptors, namely IL-1R, IL-6R and TNFR1 were upregulated in CA rats. Also, stimulation of HIF-1 alpha by systemic administration of ML228, HIF-1 alpha activator, significantly attenuated the amplified IL-6/IL-6R and TNF-alpha/TNFR1 pathway in the hippocampus of CA rats, but did not modify IL-1 beta and its receptor. Moreover, ML228 attenuated upregulated expression of Caspase-3 indicating cell apoptosis evoked by CA. Conclusion: Transient global ischemia induced by CA increases the levels of IL-1 beta, IL-6 and TNF-alpha and thereby leads to enhancement in their respective receptor in the rat hippocampus. Stabilization of HIF-1 alpha plays a role in attenuating amplified expression IL-6R, TNFR1 and Caspase-3 in the processing of transient global ischemia. Results of our study suggest that PICs contribute to cerebral injuries evoked by transient global ischemia and in this pathophysiological process activation of HIF-1 alpha improves tissues against ischemic injuries. Our data revealed specific signaling pathways in alleviating CA-evoked global cerebral ischemia by elucidating that HIF-1 alpha plays an important role in regulating PIC signal pathways and Caspase-3. The subsequent induction of HIF-1 alpha and its target signals is likely a part of the intrinsic neuroprotective effects aimed at attenuating damage as a result of global cerebral ischemia. Thus, targeting one or more of these signaling molecules has clinical implications for treatment and improvement of CA-evoked global cerebral ischemia often observed in clinics. (C) 2016 The Author(s) Published by S Karger AG, Basel
[1]Jilin Univ, Hosp 1, Dept Emergency Med, 71 Xinmin St, Changchun 130021, Jilin, Peoples R China.
[2]Jilin Prov Carcinoma Hosp, Dept Abdominal Surg, Changchun, Peoples R China.
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