【罂粟摘要】抑制长链非编码RNA00652通过cAMP/PKA通路靶向GLP-1R恢复七氟醚诱导的缺血再灌注损伤的心肌保护作用
抑制长链非编码RNA LINC00652可通过cAMP/PKA通路靶向GLP-1R恢复七氟醚诱导的小鼠心肌缺血再灌注损伤的心肌保护作用
贵州医科大学 高鸿教授课题组
翻译：安丽 编辑：佟睿 审校：曹莹
长链非编码RNA(LncRNA)和胰高血糖素样肽1受体(GLP-1R)对心脏发育和成人心脏结构的维持和功能至关重要。本研究通过环磷酸腺苷-蛋白激酶A(cAMP/PKA)途径靶向GLP-1R，探讨lncRNA LINC00652(LINC00652)对心肌缺血再灌注(I/R)损伤的影响。
利用生物信息学软件筛选与心肌缺血再灌注相关的长链非编码RNA，预测靶基因。RT-qPCR和Western blotting检测LINC00652、GLP-1R和CREB的mRNA和蛋白水平。为明确LINC00652与心肌I/R损伤的相互作用，测定了LINC00652对小鼠心功能、血流动力学、心肌组织病理改变、心肌梗死面积和心肌细胞凋亡的影响。同时检测血清白细胞介素-1(IL-1)、肿瘤坏死因子-β(TNF-α)水平。
LINC00652在心肌I/R损伤小鼠心肌细胞中高表达。GLP-1R是LINC00652的靶基因。我们还测定了I/R模型小鼠体内较高水平的LINC00652和GLP-1R。此外，si-LINC00652还能降低心肌病理改变、梗死面积、心肌细胞凋亡率和IL-1β、TNF-α水平，增加Glp-1R表达、心功能、正常血流动力学指标以及Glp-1R和CREB蛋白的表达和磷酸化。
LINC00652通过靶向GLP-1R抑制cAMP/PKA通路的激活，从而降低七氟醚对小鼠心肌I/R损伤的保护作用
Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice
Background/Aims: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor
(GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway.
Methods: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1β and TNF-α were detected.
Results: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1β and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins.
Conclusion: T aken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.