抬高型心肌梗死急诊经皮冠状动脉介入的心肌保护作用王中明㊀曾辉㊀韩风杰㊀晋辉㊀刘静㊀杭晓阳㊀郑海军㊀王晓飞454000焦作,新乡医学院附属焦作市人民医院心内科通信作者:郑海军,电子信箱:zhenghaijunxn1@DOI:10.3969/j.issn.1007-5410.2023.05.003㊀㊀ʌ摘要ɔ㊀目的㊀探讨尼可地尔联合远程缺血后适应(RIPostC)对急性ST段抬高型心肌梗死(STEMI)急诊经皮冠状动脉介入(PCI)的心肌保护作用㊂㊀方法㊀单中心㊁前瞻性㊁随机对照研究㊂连续纳入2018年1月至2021年9月在新乡医学院附属焦作市人民医院心内科病房接受PCI治疗的STEMI患者208例㊂按随机数字表法分为4组:A组(52例):常规PCI;B组(52例):RIPostC+常规PCI;C组(52例):尼可地尔+常规PCI;D组(52例):RIPostC+尼可地尔+常规PCI㊂于PCI术前后检测心肌灌注㊁心律失常㊁炎症反应㊁血管内皮功能㊁心肌损伤及心功能指标;记录术后12个月内主要不良心血管事件(MACE,包括再发心肌梗死㊁再发心力衰竭㊁心原性休克和心原性死亡)㊂㊀结果㊀(1)D组PCI术后即刻校正的TIMI血流帧数计数(CTFC)㊁术后24h Curtis-Walker评分及恶性心律失常发生率均低于A组,术后2h ST段回落幅度高于A组(均为P<0.01);(2)PCI术后48h,D组的高敏C反应蛋白(hs-CRP)㊁白细胞介素6(IL-6)㊁丙二醛(MDA)和血管内皮生长因子(VEGF)水平均低于A㊁B和C组,超氧化物歧化酶(SOD)和一氧化氮(NO)水平均高于A㊁B和C组(均为P<0.001);B㊁C组的hs-CRP㊁IL-6㊁MDA和VEGF水平均低于A组,SOD和NO水平均高于A组(均为P<0.001);(3)PCI术后12h和48h,D组的高敏心肌肌钙蛋白I(hs-cTnI)水平均低于A㊁B和C组,B㊁C组的hs-cTnI水平均低于A组(均为P<0.001);(4)PCI术后1个月和12个月,D组的左心室射血分数(LVEF)水平均高于A㊁B和C组,B㊁C组的LVEF水平均高于A组(均为P<0.001);(5)PCI术后12个月内,4组患者的MACE发生率无统计学差异(χ2=4.396,P=0.22)㊂㊀结论㊀单纯尼可地尔或RIPostC在PCI中均具有改善心肌灌注㊁拮抗氧化应激㊁抑制炎症反应㊁改善血管内皮㊁保护心肌细胞和改善心功能等作用,尼可地尔联合RIPostC的心肌保护作用明显优于单纯尼可地尔或RIPostC,联用具有协同㊁叠加效果㊂ʌ关键词ɔ㊀急性ST段抬高型心肌梗死;㊀经皮冠状动脉介入;㊀尼可地尔;㊀远程缺血后适应;缺血再灌注损伤基金项目:河南省医学科技攻关计划省部共建重大项目(SBGJ202101006)Myocardial protective effect of nicorandil combined with remote ischemic post-conditioning on acuteST-segment elevation myocardial infarction after emergency percutaneous coronary interventionWang Zhongming,Zeng Hui,Han Fengjie,Jin Hui,Liu Jing,Hang Xiaoyang,Zheng Haijun,Wang XiaofeiDepartment of Cardiology,Jiaozuo People s Hospital Affiliated to Xinxiang Medical College,Jiaozuo454000,ChinaCorresponding author:Zheng Haijun,Email:zhenghaijunxn1@ʌAbstractɔ㊀Objective㊀To investigate the myocardial protective effect of nicorandil combined withremote ischemic post-conditioning(RIPostC)on acute ST-segment elevation myocardial infarction(STEMI)after emergency percutaneous coronary intervention(PCI).㊀Methods㊀This was a single-center, prospective,randomized controlled study.A total of208STEMI patients who received PCI in the Departmentof Cardiology,Jiaozuo People s Hospital Affiliated to Xinxiang Medical College were included from January2018to September2021.Patients were randomly divided into4groups according to the number tablemethod:Group A(52cases):routine PCI;Group B(52cases):RIPostC+conventional PCI;Group C (52cases):nicorandil+conventional PCI;Group D(52cases):RIPostC+nicorandil+conventional PCI.Myocardial perfusion,arrhythmia,inflammatory response,vascular endothelial function,myocardial injury and cardiac function were detected before and after PCI.Major adverse cardiovascular events (MACE),including recurrent myocardial infarction,recurrent heart failure,cardiac shock,and cardiac death within12months,were recorded after operation.㊀Results㊀(1)The TIMI flow frame count(CTFC) corrected immediately after PCI,Curtis-Walker score24h after PCI and incidence of malignant arrhythmia were lower in group D than those in group A,the decrease of ST segment2h after operation was higher in group D than that in group A(all P<0.01).(2)48h after PCI,the levels of high-sensitivity C-reactive protein(hs-CRP),interleukin6(IL-6),malondialdehyde(MDA)and vascular endothelial growth factor (VEGF)were lower in group D than those in groups A,B and C(all P<0.001).The levels of superoxide dismutase(SOD)and nitric oxide(NO)were higher in group D than those in groups A,B and C(all P< 0.001).The levels of hs-CRP,IL-6,MDA and VEGF were lower in groups B and C than those in group A, SOD and NO were higher in groups B and C than those in group A(all P<0.001).(3)At12h and48h after PCI,the level of high-sensitivity cardiac troponin I(hs-cTnI)was lower in group D than those in groups A,B and C(all P<0.001).The hs-cTnI levels were lower in groups B and C than that in group A (all P<0.001).(4)At1and12months after PCI,left ventricular ejection fraction(LVEF)were higher in group D than those in groups A,B,and C(all P<0.001).LVEF were higher in groups B and C than those in group A(all P<0.001).(5)Within12months after PCI,there was no significant difference in the incidence of MACE among the4groups(χ2=4.396,P=0.22).㊀Conclusions Nicorandil or RIPostC alone can improve myocardial perfusion,antagonize oxidative stress,inhibit inflammatory response,improve vascular endothelium,protect cardiomyocytes and improve cardiac function during PCI.The myocardial protective effect of nicorandil combined with RIPostC is obviously better than that of nicorandil alone or RIPostC,and the combination has synergistic and superposition effect.ʌKey wordsɔ㊀Acute ST-segment elevation myocardial infarction;㊀Percutaneous coronary intervention;㊀Nicorandil;㊀Remote ischemic post-conditioning;㊀Ischemia reperfusion injury Fund program:Henan Province Medical Science and Technology Research Major Project (SBGJ202101006)㊀㊀经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)已成为急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)的有效治疗手段,但PCI中易发生心肌缺血再灌注损伤(ischemia reperfusion injury,IRI),可增加术后心肌无复流风险[1]㊂探索预防和减轻IRI安全有效的方法已成为临床亟待解决的课题㊂已有研究证实,远程缺血后适应(remote ischemic post-conditioning,RIPostC)可使心脏对缺血产生耐受效应,从而减轻IRI[2];尼可地尔也能模拟心肌缺血适应来减轻IRI[3]㊂二者联用是否会产生叠加效应?目前虽有相关研究报道[4],但多是分两组治疗前后的比较,尚未见进行多个分组㊁多个时间点的动态观察㊂本研究按照不同的治疗方法分为4组,进行多个相关指标㊁多个时间点的动态观察,旨在深入详细探讨尼可地尔联合RIPostC能否更好地预防及改善IRI,从而改善患者的心功能及临床预后㊂1㊀对象和方法1.1㊀研究对象本研究为单中心㊁前瞻性㊁随机对照研究㊂连续纳入2018年1月至2021年9月在新乡医学院附属焦作市人民医院心内科病房的STEMI患者208例,其中男性143例,女性65例,年龄47~80岁,平均(64.1ʃ5.4)岁㊂入选标准:(1)STEMI诊断标准符合‘急性ST段抬高型心肌梗死诊断和治疗指南(2019)“[5];(2)成功行冠状动脉造影显示1支及以上冠状动脉存在严重狭窄(>75%)甚至完全闭塞,未见侧支循环,发病时间<12h,符合PCI适应证;(3)成功实施PCI;(4)近1个月内未用尼可地尔;(5)患者及家属签署知情同意书㊂排除标准:(1)冠状动脉造影示冠状动脉病变严重,不适宜PCI;(2)既往有PCI及冠状动脉旁路移植术史,陈旧性心肌梗死,严重心脏瓣膜病,存在PCI的其他禁忌证;(3)手术创伤,全身或局部感染性疾病,全身自身免疫性疾病,重度肝功能不全,慢性肾脏病4期;(4)青光眼,精神病,哺乳期或妊娠妇女;(5)服用影响疗效判定的药物;(6)不能耐受或不适合RIPostC 治疗,或对尼可地尔过敏㊂本研究经焦作市人民医院伦理委员会批准(伦理批号:201706)㊂1.2㊀治疗方法术前及术后均给予常规抗凝治疗㊂将入选的208例STEMI患者按随机数字表法分为4组:A组(52例)行常规PCI治疗;B组(52例)于PCI术前1h先施行RIPostC治疗,采用TDFT-RIP-A2A型远程缺血预适应训练仪(脑心健,深圳华盈泰智能技术有限公司),将充气袖带捆扎在双侧上肢肘中线2cm处,预先设定双侧袖带压力为在基础血压上增加50mmHg,充气压迫肱动脉,以阻断双上肢远端血流5min,随后减压为0恢复血流再灌注5min,之后再次重复上述操作进行4个循环,后常规行PCI 治疗;C组(52例)术前不进行RIPostC,经靶向灌注导管给予尼可地尔注射液(北京四环科宝制药有限公司,国药准字H20120069),以0.06mg/kg(限制3~4mg/次)+生理盐水10ml稀释后10~30s推注完成,随后以2mg/h加液体稀释后静滴24h,后行常规PCI治疗,靶向灌注导管选用单轨式双腔微导管;D组(52例)在PCI术前进行RIPostC的基础上,经靶向灌注导管推注尼可地尔注射液及随后静滴尼可地尔(用量用法同B组),后行常规PCI 治疗㊂1.3㊀观察指标1.3.1㊀心肌灌注及心律失常指标㊀于PCI术前及术后即刻检测㊁计算并记录校正的TIMI血流帧数计数(corrected TIMI frame count,CTFC);于PCI术前及术后2h分别检查18导联心电图,测量并记录心电图ST段的回落幅度,ST段回落=(ðST术前-ðST术后)/ðST术前ˑ100%[6];根据术中持续心电监护及术后24h动态12导联心电图监测,记录梗死相关血管开通后24h内心律失常发生情况,采取Curtis-Walker评分标准[7]进行评分,记录ȡ3分的恶性心律失常例数㊂1.3.2㊀实验室指标㊀于PCI术前㊁术后48h检测炎症反应指标[高敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)㊁白细胞介素6(interleukin 6,IL-6)]㊁氧化应激指标[丙二醛(malondialdehyde, MDA)㊁超氧化物歧化酶(superoxide dismutase, SOD)]及血管内皮功能指标[一氧化氮(nitric oxide,NO)㊁血管内皮生长因子(vascular endothelial growth factor,VEGF)];于PCI术前㊁术后12h和48h检测心肌损伤指标血清高敏心肌肌钙蛋白I (high-sensitivity cardiac troponin I,hs-cTnI)㊂1.3.3㊀心功能指标㊀分别于术前㊁术后1个月和12个月,应用IE33型心脏彩色超声诊断系统(美国飞利浦公司)检测左心室射血分数(left ventricular ejection fraction,LVEF)㊂1.3.4㊀临床预后㊀随访记录术后12个月内主要不良心血管事件(major adverse cardiac events,MACE),包括再发心肌梗死㊁再发心力衰竭㊁心原性休克和心原性死亡㊂1.4㊀统计学方法采用SPSS22.0统计软件进行数据分析㊂正态分布的计量资料以 xʃs表示,组间比较采用单因素方差分析;非正态分布的计量资料以M(Q1,Q3)表示,组间比较采用Kruskal-Wallis H检验;多组间㊁多个时间点重复测量的计量资料比较采用两因素(时间因素和干预因素)重复测量方差分析;计数资料用百分构成比表示,组间比较采用卡方检验或Fisher精确检验㊂采用双侧检验,P<0.05为差异有统计学意义㊂2 结果2.1㊀基线资料比较4组患者的基线资料比较,差异均无统计学意义(均为P>0.05),具有可比性㊂见表1㊂2.2㊀心肌灌注及心律失常比较D组PCI术后即刻CTFC㊁术后24h Curtis-Walker评分及恶性心律失常发生率均低于A组(均为P<0.01),术后24h ST段回落幅度高于A组(P<0.01)㊂见表2㊂2.3㊀炎症反应㊁氧化应激及血管内皮功能比较PCI术后48h,D组的hs-CRP㊁IL-6㊁MDA和VEGF水平均低于A㊁B和C组,SOD和NO水平均高于A㊁B和C组(均为P<0.001);B㊁C组的hs-CRP㊁IL-6㊁MDA和VEGF水平均低于A组,SOD和NO水平均高于A组(均为P<0.001);B组与C组的上述指标水平比较,差异均无统计学意义(均为P>0.05)㊂见表3㊂2.4㊀心肌损伤标志物变化PCI术后12h和48h,D组的hs-cTnI水平均低于A㊁B和C组,B㊁C组的hs-cTnI水平均低于A组(均为P<0.001);B组与C组的hs-cTnI水平比较,差异无统计学意义(P>0.05)㊂见表4㊂2.5㊀LVEF变化PCI术后1个月和12个月,D组的LVEF水平均高于A㊁B和C组,B㊁C组的LVEF水平均高于A 组(均为P<0.001);B组与C组的LVEF水平比较,差异无统计学意义(P>0.05)㊂见表5㊂2.6㊀MACE发生情况比较PCI术后12个月内,4组患者MACE发生率分别为:A组17.3%,B组9.6%,C组7.7%,D组5.8%,依次递减㊂但经多组卡方检验,差异无统计表1㊀PCI 术前基线资料比较项目A 组(52例)B 组(52例)C 组(52例)D 组(52例)F /χ2值P 值年龄( x ʃs ,岁)64.0ʃ5.964.9ʃ5.463.9ʃ4.563.7ʃ6.60.5850.626男性[例(%)]35(67.3)38(73.1)36(69.2)34(65.4)0.7830.853体质指数( x ʃs ,kg /m 2)24.73ʃ2.3724.69ʃ3.4024.41ʃ2.9424.58ʃ2.640.1320.941糖尿病[例(%)]18(34.6)21(40.4)20(38.5)17(32.7)0.8290.842高血压[例(%)]23(44.2)24(46.2)21(40.4)25(48.1)0.6810.878靶血管病变部位[例(%)]㊀左前降支43(82.7)39(75.0)41(78.8)42(80.8) 1.0260.795㊀左回旋支17(32.7)20(38.5)22(42.3)19(36.5) 1.0670.785㊀右冠状动脉27(51.9)29(55.8)23(44.2)25(48.1) 1.5380.673Gensini 评分( x ʃs ,分)53.71ʃ5.0451.73ʃ6.4252.76ʃ4.6851.84ʃ6.88 1.3030.275发病至就诊时间(x ʃs ,min)70.87ʃ6.9174.02ʃ8.5070.35ʃ9.4072.71ʃ8.33 2.1500.095PCI 用时(x ʃs ,min)33.65ʃ4.4833.48ʃ5.4833.83ʃ5.3433.19ʃ5.250.1430.934㊀㊀注:PCI:经皮冠状动脉介入治疗;A 组:常规PCI;B 组:RIPostC +常规PCI;C 组:尼可地尔+常规PCI;D 组:RIPostC +尼可地尔+常规PCI表2㊀PCI 术前后CTFC㊁ST 段回落及心律失常发生情况比较组别例数术前CTFC(x ʃs ,帧)术后即刻CTFC( x ʃs ,帧)术后2h ST 段回落幅度(x ʃs ,%)术后24hCurtis-Walker 评分[M(Q 1,Q 3),分]恶性心律失常[例(%)]A 组5280.43ʃ2.5825.64ʃ1.9584.76ʃ5.54 1.50(1.00,2.00)㊀12(23.1)B 组5280.42ʃ2.4024.85ʃ1.4685.62ʃ6.83 1.00(0.00,2.00)㊀8(15.4)C 组5279.81ʃ2.2924.50ʃ1.5586.21ʃ5.94 1.00(0.00,2.00)㊀6(11.5)D 组5280.51ʃ2.4124.21ʃ1.7888.55ʃ5.17 1.00(0.00,2.00)㊀2(3.8)F /H /χ2值0.926 6.952 3.9319.4068.600P 值0.4290.0000.0090.0240.035两两比较P 值㊀A 组vs .B 组0.9850.0230.4600.2300.343㊀A 组vs .C 组0.1950.0090.2110.0840.120㊀A 组vs .D 组0.8680.0000.0010.0020.004㊀B 组vs .C 组0.2010.7260.6070.6750.539㊀B 组vs .D 组0.8530.0250.0120.0940.090㊀C 组vs .D 组0.1440.0570.0450.1830.269㊀㊀注:PCI:经皮冠状动脉介入治疗;CTFC:校正的TIMI 血流帧数计数;A 组:常规PCI;B 组:RIPostC +常规PCI;C 组:尼可地尔+常规PCI;D 组:RIPostC +尼可地尔+常规PCI表3㊀PCI 术前及术后48h 炎症反应㊁氧化应激及血管内皮功能指标比较(x ʃs )指标时间A 组(52例)B 组(52例)C 组(52例)D 组(52例)单因素方差分析F (3,204)值P 值hs-CRP(mg /L)术前 5.71ʃ0.945.76ʃ0.855.86ʃ0.955.88ʃ0.800.4450.721术后48h12.42ʃ1.5912.13ʃ1.3811.69ʃ1.3411.32ʃ1.22 6.2680.000IL-6(ng /L)术前12.22ʃ1.6512.72ʃ1.7312.52ʃ2.0512.76ʃ1.64 1.0090.390术后48h22.04ʃ3.0520.59ʃ2.9220.13ʃ3.6218.76ʃ2.829.8240.000MDA(μmol /L)术前 2.67ʃ0.50 2.71ʃ0.34 2.74ʃ0.43 2.73ʃ0.400.3450.793术后48h5.11ʃ0.47 4.78ʃ0.56 4.73ʃ0.41 4.42ʃ0.3919.4340.000SOD(kU /L)术前71.77ʃ12.6668.59ʃ9.5168.86ʃ10.7370.92ʃ10.86 1.0430.375术后48h62.11ʃ10.2270.15ʃ11.9871.60ʃ9.0576.41ʃ13.5912.2630.000NO(μmol /L)术前44.57ʃ4.6044.92ʃ5.5045.00ʃ4.5443.86ʃ4.890.5850.626术后48h43.28ʃ6.6847.21ʃ5.2148.62ʃ6.1352.35ʃ6.6718.9970.000VEGF(ng /L)术前129.70ʃ11.13132.37ʃ16.21131.10ʃ12.44130.05ʃ13.790.4090.747术后48h132.64ʃ13.35124.57ʃ14.60121.76ʃ16.88110.83ʃ14.3419.1790.000㊀㊀注:PCI:经皮冠状动脉介入治疗;A 组:常规PCI;B 组:RIPostC +常规PCI;C 组:尼可地尔+常规PCI;D 组:RIPostC +尼可地尔+常规PCI;hs-CRP:高敏C 反应蛋白;IL-6:白细胞介素6;MDA:丙二醛;SOD:超氧化物歧化酶;NO:一氧化氮;VEGF:血管内皮生长因子学意义(χ2=4.396,P =0.22)㊂见表6㊂3㊀讨论本研究显示,RIPostC 与尼可地尔联用的急性STEMI 患者PCI 术后即刻CTFC㊁术后24h Curtis-Walker 评分及恶性心律失常发生率均低于常规PCI,术后24h ST 段回落幅度高于常规PCI,表明RIPostC 与尼可地尔联用对患者PCI 术后血流灌注表4㊀PCI术前后血清hs-cTnI水平比较( xʃs,μg/L)组别例数术前术后12h术后48hA组520.88ʃ0.142.42ʃ0.361.49ʃ0.18B组520.88ʃ0.122.27ʃ0.27a1.42ʃ0.16a C组520.89ʃ0.142.25ʃ0.26b1.41ʃ0.12b D组520.91ʃ0.112.08ʃ0.26b1.32ʃ0.16b 单因素方差F(3,204)值0.71612.01910.151㊀分析P值0.543<0.001<0.001两因素重复测F时间=2538.276,F组间=14.379,F交互=8.643㊀量方差分析P时间<0.001,P组间<0.001,P交互<0.001㊀㊀注:PCI:经皮冠状动脉介入治疗;hs-cTnI:高敏心肌肌钙蛋白I; A组:常规PCI;B组:RIPostC+常规PCI;C组:尼可地尔+常规PCI;D 组:RIPostC+尼可地尔+常规PCI;同时间点与A组比较,a P< 0.05,b P<0.01表5㊀PCI术前后LVEF比较( xʃs,%)组别例数术前术后1个月术后12个月A组5250.25ʃ2.7753.76ʃ3.3854.11ʃ3.13B组5250.05ʃ2.7055.32ʃ4.06a56.26ʃ3.85a C组5249.84ʃ3.2055.78ʃ4.19b56.91ʃ5.41b D组5250.06ʃ2.6757.98ʃ3.86b58.79ʃ4.64b 单因素方差F(3,204)值0.18210.42010.264㊀分析P值0.908<0.001<0.001两因素重复测F时间=210.948,F组间=17.738,F交互=4.987㊀量方差分析P时间<0.001,P组间<0.001,P交互<0.001㊀㊀注:PCI:经皮冠状动脉介入治疗;LVEF:左心室射血分数;A组:常规PCI;B组:RIPostC+常规PCI;C组:尼可地尔+常规PCI;D组: RIPostC+尼可地尔+常规PCI;同时间点与A组比较,a P<0.05, b P<0.01表6㊀PCI术后12个月内MACE发生情况比较[例(%)]组别例数再发心肌梗死再发心力衰竭心原性休克心原性死亡合计A组523(5.8)4(7.7)1(1.9)1(1.9)9(17.3) B组522(3.8)2(3.8)1(1.9)0(0.0)5(9.6) C组522(3.8)2(3.8)0(0.0)0(0.0)4(7.7) D组522(3.8)1(1.9)0(0.0)0(0.0)3(5.8)㊀㊀注:PCI:经皮冠状动脉介入治疗;MACE:主要不良心血管事件; A组:常规PCI;B组:RIPostC+常规PCI;C组:尼可地尔+常规PCI;D 组:RIPostC+尼可地尔+常规PCI;再发心肌梗死包括支架内血栓形成㊁靶病变再狭窄及再次血运重建的改善效果最佳,术后24h ST段回落幅度最大,心律失常发生率最低,二者联用已显示出协同㊁叠加效应㊂而任何一种方法单用与常规PCI比较尚未出现统计学上的差异,可能是样本量较小所致㊂分析原因,RIPostC与缺血后适应有着相同的保护机制[8],短时间的缺血引起机体释放腺苷㊁缓激肽㊁阿片类物质㊁SOD和NO等内源活性物质,其作用于各自相应的受体,通过神经和体液两种途径传递生物信号,激活线粒体K ATP,抑制线粒体通透性转化孔的开放[9],使心脏对缺血产生耐受效应,从而减轻心肌的缺血再灌注损伤[10]㊂尼可地尔可选择性地激活血管平滑肌细胞膜K ATP通道,直接舒张微小冠状动脉,增加心肌灌注[11];还可作用于心肌细胞线粒体膜K ATP通道,参与心肌细胞代谢调节维护线粒体功能,减轻缺血再灌注损伤[12]㊂其次,尼可地尔还具有硝酸酯类药物的作用,其代谢产生NO㊂NO可扩张体循环血管平滑肌,降低心脏前㊁后负荷,降低心肌耗氧量[13]㊂此外,尼可地尔通过拮抗二磷酸腺苷诱导的血小板聚集,抑制冠状动脉血栓形成[14]㊂IL-6作用于肝脏促使产生hs-CRP,诱发炎症的连锁放大效应[15];缺氧促使心肌细胞产生大量氧自由基,其作用于细胞膜上的不饱和脂肪酸使膜脂质发生过氧化反应,氧化终产物为MDA㊂MDA能客观地反映组织过氧化损伤程度[16];SOD可拮抗与阻断氧自由基对膜脂质的过氧化反应,发挥其保护作用[17]㊂血管损伤可促进VEGF分泌,VEGF促进血管内皮细胞增殖和血管新生[18];NO不仅可舒张血管平滑肌,抑制血小板激活㊁吸附和聚集,还可调节VEGF促进血管新生[19]㊂因此,血管内皮损伤会导致VEGF水平升高,NO水平降低㊂本研究中4组患者的hs-CRP㊁IL-6㊁MDA和VEGF指标均表现在PCI术后24h达高峰,随后逐渐下降;而对机体具有保护作用的NO㊁SOD在PCI 术后24h降至最低谷,随后逐渐升高㊂造成这种波动的原因在于PCI中伴随IRI,诱发氧化应激反应,心肌细胞内的ATP合成减少,导致细胞内酸中毒㊁Ca2+过量,氧自由基大量生成,导致PCI术后24h MDA升高,SOD降低;同时伴随血管内皮功能损伤,表现为PCI术后NO降低,VEGF升高㊂PCI中球囊扩张和支架置入常造成内皮的机械性损伤,在缺血再灌注损伤基础上进一步加重炎症反应,表现为PCI术后hs-CRP㊁IL-6的升高㊂术后48h可见,D 组的hs-CRP㊁IL-6㊁MDA和VEGF水平均低于A㊁B 和C组,SOD和NO水平均高于A㊁B和C组;B㊁C 组的hs-CRP㊁IL-6㊁MDA和VEGF水平均低于A组, SOD和NO水平均高于A组㊂表明尼可地尔与RIPostC单一应用均能有效拮抗氧化应激㊁炎症反应及保护血管内皮,且二者之间无显著差异㊂而二者联用其保护作用协同叠加,优于其任何单一疗效㊂4组患者的hs-cTnI水平均是在PCI术后12h 达高峰,随后逐渐下降㊂应用重复测量的方差分析,B㊁C组的hs-cTnI水平均低于A组,D组的hs-cTnI水平均低于A㊁B和C组,表明尼可地尔与RIPostC联用能使患者PCI术后的心肌损伤最轻,二者联用对心肌的保护效果最佳㊂经过12个月的随访,发现D组的LVEF水平均高于A㊁B和C组, B㊁C的LVEF水平均高于A组,表明尼可地尔与RIPostC联用能使患者PCI术后的LVEF水平最高,这恰好与PCI术后D组的心肌损伤最轻相一致㊂术后12个月内,4组患者MACE发生率虽然经多组卡方检验无统计学差异,但仍显示出递减趋势,A 组>B组>C组>D组,表明二者联用可能会使MACE 发生率降低,科学的结论有待进一步研究㊂综上所述,尼可地尔联合RIPostC的心肌保护作用强于二者其中的任何单一方法㊂但本研究存在一定局限性,作为单中心研究,样本量较少,观察时间较短,所得的结果不能排除数据偏倚造成的影响㊂更科学的结论还需今后多中心㊁大样本㊁观察时间足够长的随机对照前瞻性研究证实㊂利益冲突:无参㊀考㊀文㊀献[1]林书坡,郑艳秋,郑春贵,等.前列地尔对急性ST段抬高型心肌梗死患者经PCI后心肌缺血再灌注㊁血清炎症因子㊁氧化应激和血管内皮功能的影响[J].中国老年学杂志,2020,40(24):5153-5156.DOI:10.3969/j.issn.1005-9202.2020.24.001.㊀Lin SP,Zheng YQ,Zheng CG,et al.Effects of alprostadil onmyocardial 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