BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technol...BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.展开更多
Our knowledge and understanding of the pathophysiology of coronary atherosclerosis has increased enormously over the last 20 years.Reperfusion through thrombolysis or percutaneous coronary angioplasty is the standard ...Our knowledge and understanding of the pathophysiology of coronary atherosclerosis has increased enormously over the last 20 years.Reperfusion through thrombolysis or percutaneous coronary angioplasty is the standard treatment for preventing acute myocardial infarction.Early reperfusion is an absolute prerequisite for survival of the ischemic myocardium,but reperfusion itself may lead to accelerated and additional myocardial injury beyond that generated by ischemia alone.These outcomes,in a range of reperfusion-associated pathologies,are collectively termed "reperfusion injuries".Reactive oxygen species are known to be produced in large quantities in the first few minutes of the post-ischemia reperfusion process.Similarly,scientific evidence from the last 15 years has suggested that melatonin has beneficial effects on the cardiovascular system.The presence of vascular melatoninergic receptor binding sites has been demonstrated;these receptors are functionally linked to vasoconstrictor or vasodilatory effects of melatonin.It has been shown that patients with coronary heart disease have a low melatonin production rate,especially those with higher risk of cardiac infarction and/or sudden death.Melatonin attenuates molecular and cellular damage resulting from cardiac ischemia-reperfusion in which destructive free radicals are involved.展开更多
Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological pro...Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological process is known as myocardial ischemia-reperfusion injury(I/R).But,the mechanism of I/R is not fully understood and there is no available effective treatment for I/R.This article will review the mechanisms of occurrence and treatments currently found for I/R.展开更多
目的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。方法单中心、前瞻性、随机对照研究。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...目的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。方法单中心、前瞻性、随机对照研究。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。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PCI。于PCI术前后检测心肌灌注、心律失常、炎症反应、血管内皮功能、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、再发心力衰竭、心原性休克和心原性死亡)。结果(1)D组PCI术后即刻校正的TIMI血流帧数计数(CTFC)、术后24 h Curtis-Walker评分及恶性心律失常发生率均低于A组,术后2 h ST段回落幅度高于A组(均为P<0.01);(2)PCI术后48 h,D组的高敏C反应蛋白(hs-CRP)、白细胞介素6(IL-6)、丙二醛(MDA)和血管内皮生长因子(VEGF)水平均低于A、B和C组,超氧化物歧化酶(SOD)和一氧化氮(NO)水平均高于A、B和C组(均为P<0.001);B、C组的hs-CRP、IL-6、MDA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12 h和48 h,D组的高敏心肌肌钙蛋白I(hs-cTnI)水平均低于A、B和C组,B、C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A、B和C组,B、C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(χ^(2)=4.396,P=0.22)。结论单纯尼可地尔或RIPostC在PCI中均具有改善心肌灌注、拮抗氧化应激、抑制炎症反应、改善血管内皮、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、叠加效果。展开更多
基金National Natural Science Foundation of China(81670220,31270992,and 30800215)Guangdong Provincial Natural Science Foundation(2014A030313086)+2 种基金Guangdong Provincial Science and Technology Plan Project(2015A020212013)Guangzhou Science and Technology Project(201804010007)This research was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University([2019]176).
文摘BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.
文摘Our knowledge and understanding of the pathophysiology of coronary atherosclerosis has increased enormously over the last 20 years.Reperfusion through thrombolysis or percutaneous coronary angioplasty is the standard treatment for preventing acute myocardial infarction.Early reperfusion is an absolute prerequisite for survival of the ischemic myocardium,but reperfusion itself may lead to accelerated and additional myocardial injury beyond that generated by ischemia alone.These outcomes,in a range of reperfusion-associated pathologies,are collectively termed "reperfusion injuries".Reactive oxygen species are known to be produced in large quantities in the first few minutes of the post-ischemia reperfusion process.Similarly,scientific evidence from the last 15 years has suggested that melatonin has beneficial effects on the cardiovascular system.The presence of vascular melatoninergic receptor binding sites has been demonstrated;these receptors are functionally linked to vasoconstrictor or vasodilatory effects of melatonin.It has been shown that patients with coronary heart disease have a low melatonin production rate,especially those with higher risk of cardiac infarction and/or sudden death.Melatonin attenuates molecular and cellular damage resulting from cardiac ischemia-reperfusion in which destructive free radicals are involved.
文摘Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological process is known as myocardial ischemia-reperfusion injury(I/R).But,the mechanism of I/R is not fully understood and there is no available effective treatment for I/R.This article will review the mechanisms of occurrence and treatments currently found for I/R.
文摘目的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。方法单中心、前瞻性、随机对照研究。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。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PCI。于PCI术前后检测心肌灌注、心律失常、炎症反应、血管内皮功能、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、再发心力衰竭、心原性休克和心原性死亡)。结果(1)D组PCI术后即刻校正的TIMI血流帧数计数(CTFC)、术后24 h Curtis-Walker评分及恶性心律失常发生率均低于A组,术后2 h ST段回落幅度高于A组(均为P<0.01);(2)PCI术后48 h,D组的高敏C反应蛋白(hs-CRP)、白细胞介素6(IL-6)、丙二醛(MDA)和血管内皮生长因子(VEGF)水平均低于A、B和C组,超氧化物歧化酶(SOD)和一氧化氮(NO)水平均高于A、B和C组(均为P<0.001);B、C组的hs-CRP、IL-6、MDA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12 h和48 h,D组的高敏心肌肌钙蛋白I(hs-cTnI)水平均低于A、B和C组,B、C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A、B和C组,B、C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(χ^(2)=4.396,P=0.22)。结论单纯尼可地尔或RIPostC在PCI中均具有改善心肌灌注、拮抗氧化应激、抑制炎症反应、改善血管内皮、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、叠加效果。
