七氟醚预处理在二尖瓣置换手术的心肌保护作用:一项随机对照研究及lncRNA分析

Cardiaoprotective effect of sevoflurane preconditioning in patients undergoing mitral replacement surgery: a randomized controlled trial with lncRNA analysis

目的探讨七氟醚(sevoflurane)预处理对体外循环下行二尖瓣膜置换患者的心脏保护作用及其机制。方法纳入我院心脏外科2017年5-11月收治的40例接受二尖瓣置换手术的患者(17例男性和23例女性),平均年龄48岁,BMI:(22.7±2.6)kg/m2。根据随机数字表法将患者分为七氟醚预处理(SEV)组和对照(CON)组(n=20),SEV组患者体外循环前接受七氟醚持续吸入维持麻醉,而CON组采用丙泊酚维持麻醉。采集术前、术后2、24 h血液,检测c Tn I浓度;心脏彩超评估术前、术后24 h左室缩短分数和射血分数,记录ICU停留时间及住院时间;分别在体外循环开始前取得两组患者取心房肌标本(n=5),进行lncRNA测序和分析。结果SEV组患者:术后2 h[0.58(0.33,0.90)ng/m L vs 1.06(0.55、2.16)ng/m L,P<0.05]和24 h[0.66(0.38、1.02)ng/m L vs 1.09(0.72、1.54)ng/m L,P<0.05]的c Tn I浓度均显著低于CON组;术后24 h左室缩短分数值[(39.8±3.3)%vs(33.9±2.8)%,P<0.05)和左室射血分数[(70.5±4.0)%vs(62.7±4.2)%,P<0.05]显著高于CON组;ICU停留时间[(68±18)h vs(83±26)h,P<0.05]显著短于CON组。两组患者的住院时间差异无统计学意义(P>0.05)。lncRNA分析出73个上调和95个下调基因,结果提示心肌细胞凋亡相关的lncRNA通路可能参与七氟醚心脏保护。结论体外循环前七氟醚预处理对行二尖瓣置换手术的患者具有早期心肌保护作用;心肌细胞凋亡相关lncRNA通路可能是七氟醚预处理心肌保护的潜在作用靶点。

ObjectiveTo investigate the cardioprotective effects of sevoflurane preconditioning in patients undergoing mitral valve replacement under cardiopulmonary bypass and explore the underlying mechanisms by analyzing the expression profile of long noncoding RNAs （lncRNAs） in human cardiac tissue. MethodsThis randomized controlled trial included a total of 40 patients [17 male and 23 female patients with a mean age of 48 years （median, 49 years） and a mean body mass index of 22.7±2.6 kg/m2] undergoing mitral valve replacement under cardiopulmonary bypass between May and November 2017. The patients were randomized to undergo mitral valve replacement with sevoflurane preconditioning before cardiopulmonary bypass （SEV group, n=20） or without sevoflurane preconditioning （control group, n=20）. Serum levels of cardiac troponin I （cTnI） was tested before and at 2 h and 24 h after surgery, and the left ventricular fractional shortening and ejection fraction were determined by cardiac ultrasonography before and at 24 h after surgery. The length of postoperative ICU stay and length of hospital stay of the patients were recorded. For 5 patients from each group, RNA-seq analysis was performed using the left atrial myocardial specimens collected during the surgery. ResultsCompared with those in the control group, the patients in SEV group had significantly lower serum levels of cTnI at 2 h [1.06 （0.55, 2.16） vs 0.58 （0.33, 0.90） ng/mL, P〈0.05] and at 24 h after the surgery [1.09 （0.72, 1.54） vs 0.66 （0.38, 1.02） ng/mL, P〈0.05]. At 24 h after the surgery, the patients in SEV group showed significantly higher values of both fractional shortening [（39.8±3.3）% vs （33.9±2.8）%, P〈0.05] and ejection fraction [（70.5±4.0）% vs （62.7±4.2）%, P〈0.05] than those in the control group. The length of ICU stay was significantly shorter in SEV group than in the control group （68±18 vs 83±26 h, P〈0.05）, but the length of hospital stay did not differ significantly between the 2 groups （P〉0.05）. The results of lncRNA analysis identified 73 upregulated lncRNAs and 95 downregulated lncRNAs in the myocardial specimens, and KEGG analysis suggested possible associations of several apoptosis-related pathways with the cardioprotective effects of sevoflurane preconditioning. ConclusionSevoflurane preconditioning before cardiopulmonary bypass can reduce myocardial injury early after mitral valve replacement, and thus can be an optimal anesthesia strategy for this operation. The lncRNA pathways in relation with apoptosis may provide new insights into the mechanism of cardioprotective effects of sevoflurane preconditioning.