Abstract：
Dexmedetomidine (Dex) is widely used in the sedation in intensive care units and as an anesthetic adjunct. Considering the anti-inflammatory and antioxidant properties of Dex, we applied in vivo rat model as well as in vitro cardiomyocyte models (embryonic rat cardiomyocytes H9c2 cells and neonatal rat cardiomyocytes, NRCMs) to evaluate the effects of Dex against myocardial ischemia reperfusion (I/R) injury. Transcriptomic sequencing for gene expression in heart tissues from control rats and Dex-treated rats identified that genes related to fatty acid metabolism were significantly regulated by Dex. Among these genes, the elongation of long-chain fatty acids (ELOVL) family member 6 (Elovl6) was most increased upon Dex-treatment. By comparing the effects of Dex on both wild type and Elovl6-knockdown H9c2 cells and NRCMs under oxygen-glucose deprivation/reoxygenation (OGD/R) challenge, we found that Elovl6 knockdown attenuated the protection efficiency of Dex, which was supported by the cytotoxicity endpoints (cell viability and lactate dehydrogenase release) and apoptosis as well as key gene expressions. These results indicate that Dex exhibited the protective function against myocardial I/R injury via fatty acid metabolism pathways and Elovl6 plays a key role in the process, which was further confirmed using palmitate exposure in both cells, as well as in an in vivo rat model. Overall, this study systematically evaluates the protective effects of Dex on the myocardial I/R injury and provides better understanding on the fatty acid metabolism underlying the beneficial effects of Dex.
摘要：
右美托咪定（Dex）广泛用于重症监护病房的镇静和麻醉辅助。考虑到Dex的抗炎和抗氧化特性，我们应用了体内大鼠模型以及体外心肌细胞模型（胚胎大鼠心肌细胞H9c2细胞和新生大鼠心肌细胞，NRCMs)评价Dex抗心肌缺血再灌注(I/R)毁伤的感化。来自对照大鼠和Dex处理的大鼠的心脏组织中的基因表达的转录组测序鉴定,与脂肪酸代谢相关的基因被Dex显著调节。在这些基因中,在Dex处理后,长链脂肪酸(ELOVL)家族成员6(Elovl6)的伸长增加最多。通过比较Dex在氧-葡萄糖剥夺/复氧（OGD/R）攻击下对野生型和Elovl6敲低H9c2细胞和NRCM的影响，我们发现Elovl6敲低减弱了Dex的保护效率，这得到了细胞毒性终点（细胞活力和乳酸脱氢酶释放）和细胞凋亡以及关键基因表达的支持。这些结果表明，Dex通过脂肪酸代谢途径对心肌I/R损伤具有保护作用，Elovl6在该过程中起关键作用，这进一步证实了使用棕榈酸在两个细胞中的暴露，以及体内大鼠模型。总的来说,本研究系统评价了Dex对心肌I/R损伤的保护作用,并对Dex有益作用的潜在脂肪酸代谢提供了更好的理解.
