右美托咪定对心肌缺血再灌注后eNOS、HIF-1α、AQP1水平的影响

Effect of dexmedetomidine on eNOS,HIF-1α and AQP1 level after myocardial ischemia-reperfusion

目的:观察右美托咪定(Dexmedetomidine,DEX)对心肌缺血再灌注后丙二醛(malondialdehyde,MDA)、内皮源性一氧化氮合酶(endothelial nitric oxide synthase,eNOS)、缺氧诱导因子1α(hypoxia-inducible factor 1α,HIF-1α)、水通道蛋白1(aquaporin 1,AQP1)水平的影响,探讨抑制体外循环心肺转流(cardiopulmonary bypass,CPB)术后低心排血量状态的细胞分子机制。方法:选取2021年5月—2022年6月在南通大学附属医院行CPB心内直视择期手术患者45例,按随机数字表法分为常规麻醉组(对照组)、常规麻醉+低剂量DEX组(DEX1组)和常规麻醉+高剂量DEX组(DEX2组),每组15例。常规麻醉:面罩吸氧去氮后,依次静脉注射依托咪酯、咪达唑仑、丙泊酚、维库溴铵、舒芬太尼行麻醉诱导,肌松后气管插管、机械控制呼吸;使用丙泊酚、瑞芬太尼、维库溴铵行麻醉维持,维持术中血流动力学稳定。DEX1组:常规麻醉基础上,麻醉前10 min单次予0.3μg/kg DEX静脉慢注,再予0.8μg/(kg·h)DEX静脉维持;DEX2组:在常规麻醉基础上,麻醉前10 min单次予0.6μg/kg DEX静脉慢注,再予1.2μg/(kg·h)DEX静脉维持。比较3组患者一般情况和MDA、HIF-1α、eNOS、AQP1水平。结果:各组患者基本情况差异无统计学意义(P>0.05)。患者心脏复跳(T1)、复跳后15 min(T2)时MDA水平与麻醉诱导前(T0)比较,对照组和DEX1组显著增高(P<0.05),DEX2组差异无统计学意义(P>0.05);与对照组比较,T1、T2时DEX2组显著降低(P<0.05),DEX1组差异无统计学意义(P>0.05)。T2时DEX1组HIF-1α、eNOS、AQP1水平与对照组比较差异无统计学意义(P>0.05),DEX2组较对照组显著增高(P<0.05);与DEX1组比较,DEX2组HIF-1α、eNOS、AQP1水平均显著增加(P<0.05)。结论:DEX术前预处理可能是干预CPB心内直视手术后心肌缺血再灌注损伤的对策,内皮细胞eNOS/HIF-1α-AQP1可能是临床改善术后低心排血量状态的重要信号通路。

Objective:To observe the effects of dexmedetomidine(DEX)on levels of malondialdehyde(MDA),endothelial nitric oxide synthase(eNOS),hypoxia-inducible factor 1α(HIF-1α)and aquaporin 1(AQP1)after myocardial ischemia-reperfusion;and to explore the cellular and molecular mechanism of inhibiting low cardiac output after the cardiopulmonary bypass(CPB)surgery.Methods:A total of 45 patients undergoing elective CPB open-heart surgery in Affiliated Hospital of Nantong University from May 2021 to June 2022 were selected and divided into routine anesthesia group(control group),routine anesthesia+low-dose DEX group(DEX1 group)and routine anesthesia+high-dose DEX group(DEX2 group),with 15 cases in each group.Routine anesthesia:After oxygen and nitrogen removal in the mask,etomidate,midazolam,propofol,vecuronium bromide and sufentanil were sequentially intravenously injected to induce anesthesia.After muscle relaxation,endotracheal intubation was performed and breathing was mechanically controlled.Propofol,remifentanil and vecuronium bromide were used to maintain the hemodynamic stability during the operation.DEX1 group:Based on conventional anesthesia,10 min before anesthesia,0.3μg/kg DEX was injected intravenously,and 0.8μg/(kg·h)DEX was maintained intravenously.DEX2 group:On the basis of conventional anesthesia,0.6μg/kg DEX was injected intravenously 10 min before anesthesia,and then 1.2μg/(kg·h)DEX was maintained intravenously.The general situation and the levels of MDA,HIF-1α,eNOS and AQP1 in the above three groups were compared.Results:There was no statistically significant difference in the basic condition among all groups(P>0.05).Compared with before anesthesia induction(T0),the MDA levels of patients at cardioversion(T1)and 15 min after cardioversion(T2)were significantly higher in the control group and DEX1 group(P<0.05),while there was no statistically significant difference in DEX2 group(P>0.05).Compared with the control group,the DEX2 group showed a significant decrease(P<0.05)at T1 and T2,while the DEX1 group showed no statistically significant difference(P>0.05).There was no statistically significant difference in the levels of HIF-1α,eNOS,and AQP1 between the DEX1 group and the control group at T2(P>0.05),while the DEX2 group showed a significant increase compared with the control group(P<0.05).Compared with the DEX1 group,the levels of HIF-1α,eNOS,and AQP1 in the DEX2 group were significantly increased(P<0.05).Conclusion:Preconditioning with DEX before surgery may be a strategy to intervene myocardial ischemia-reperfusion injury after open heart surgery of CPB,and eNOS/HIF-1α-AQP1 in endothelial cells may be an important signaling pathway to improve postoperative low cardiac output.