Hyperglycemia attenuates remifentanil postconditioning-induced cardioprotection against hypoxia/reoxygenation injury in H9c2 cardiomyoblasts

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• 作者：Lijian Chen ; PhD^a ; ¹ ; Manli Chen ; MD^a ; ¹ ; Jian Du ; PhD^b ; ^c ; Lijuan Wan ; MD^b ; ^c ; Lei Zhang ; MD^a ; Erwei Gu ; MD^a ; ^{ay_guew_mz@163.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Hypoxia/reoxygenation injury ; Remifentanil postconditioning ; Hyperglycemia ; Endoplasmic reticulum stress
• 刊名：Journal of Surgical Research
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：203
• 期：2
• 页码：483-490
• 全文大小：1649 K

文摘

Hyperglycemia is proposed to be an independent risk factor for cardiovascular morbidity and mortality. Preclinical studies suggest that diabetes mellitus exacerbates myocardial ischemia/reperfusion injury and attenuates the effects of cardioprotective strategies. The cardioprotective effects of postconditioning with the opioid analgesic remifentanil against ischemia/reperfusion injury under the hyperglycemic condition remain contradictory. Therefore, the aim of this study was to investigate the mechanisms by which hyperglycemia affects cardioprotection induced by remifentanil postconditioning.

Materials and methods

H9c2 cardiomyoblasts were cultured under the normoglycemic or hyperglycemic condition. Cells were exposed to hypoxia/reoxygenation (H/R) injury followed by hypoxia postconditioning (HPC group) or remifentanil postconditioning (RPC group). Cell viability, injury, and apoptosis were measured after each postconditioning treatment. Activation of endoplasmic reticulum stress (ERS) was analyzed by examining the protein levels of GRP78, CHOP, cleaved caspase-12 and cleaved caspase-3.

Results

RPC significantly increased cell viability and reduced apoptosis in normoglycemic cardiomyoblasts, but not in hyperglycemic cardiomyoblasts. HPC and RPC markedly decreased the upregulation of GRP78, CHOP, cleaved caspase 12, and cleaved caspase 3 in response to H/R injury under the normoglycemic condition. Hyperglycemia significantly increased these ERS-associated biomarkers and apoptosis, which could not be reduced by HPC or RPC.

Conclusions

Remifentanil postconditioning protected cardiomyoblasts from H/R injury under normoglycemia, at least in part, through inhibiting ERS-induced apoptosis. Hyperglycemia attenuated the cardioprotection conferred by remifentanil postconditioning, likely as a result of the exacerbated ERS. Inhibiting the ERS response may be an attractive strategy to enhance the cardioprotective effects of postconditioning in diabetic patients.