地氟烷预处理对大鼠心肌梗死的保护作用及相关机制研究
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摘要
目的观察地氟烷预处理对大鼠心肌梗死的保护作用,并探讨其相关的机制。方法将60只Wistar大鼠随机分为4组,A组(假手术组)、B组(心肌梗死+地氟烷预处理组)、C组(心肌梗死组)、D组(心肌梗死+STAT3激动剂+地氟烷预处理组),每组15只,检测各组大鼠心肌梗死面积、左心室收缩压和舒张压的差异。运用Western blot法检测信号转导与转录激活因子-3(STAT3)表达和其磷酸化水平的差异。结果①4组大鼠心肌梗死面积分别为0%、(32.7±1.4)%、(58.1±2.7)%、(51.1±1.8)%,其中C组的心肌梗死面积最大,其次为D组、B组,C组明显高于B组和D组,差异具有统计学意义(P<0.05,P<0.01)。②冠状动脉闭塞形成后,4组大鼠收缩压和舒张压分别为(98±6)、(96±8)、(76±4)、(84±3)mmHg和(71±3)、(73±3)、(55±4)、(64±2)mmHg,C组大鼠收缩压和舒张压最低,其次为D组(均P<0.05),B组与A组差异无统计学意义。③4组大鼠STAT3和其磷酸化水平的差异,C组STAT3、p-STAT3的表达最高,其次为D组、B组,C组明显高于B组和D组,差异具有统计学意义(均P<0.01)。结论地氟烷预处理对大鼠心肌梗死具有一定的保护作用,其机制可能与STAT3和其磷酸化水平有关。
Objective To investigate the protective effect of desflurane preconditioning on myocardial infarction in rats and to explore its related mechanisms.Methods Sixty Wistars were randomly divided into 4 groups,group A(sham operation group),group B(myocardial infarction+desflurane and preconditioning group),group C(myocardial infarction group),group D(myocardial infarction+STAT3 activation+desflurane preconditioning group),15 rats in each group.The differences of myocardial infarct size,left ventricular systolic pressure and diastolic blood pressure were detected in each group.Western blotting was used to detect the difference between signal transduction and activators of transduction-3(STAT3)and its phosphorylation level.Results The area of myocardial infarction in the four groups was 0%,(32.7±1.4)%,(58.1±2.7)% and(51.1±1.8)%,respectively.The myocardial infarct size of group C was the largest,followed by group D and group B.The area in group C was significantly higher than that in group B and group D(P<0.05,P<0.01).After the formation of coronary artery occlusion,the systolic and diastolic blood pressures of the four groups were(98±6),(96±8),(76±4),(84±3)mmHg,and(71±3),(73±3),(55±4),(64±2)mmHg,rats in the group C had the lowest systolic and diastolic blood pressure,followed by group D(P<0.05),there was no significant difference between group C and group A.The expression of STAT3 and p-STAT3 was the highest in group C,followed by group D and group B.The expression of STAT3 and p-STAT3 in group C was significantly higher than that in the group B and group D(all P<0.01).Conclusion Desflurane preconditioning has a protective effect on myocardial infarction in rats,and its mechanism may be related to STAT3 and its phosphorylation level.
Objective To investigate the protective effect of desflurane preconditioning on myocardial infarction in rats and to explore its related mechanisms.Methods Sixty Wistars were randomly divided into 4 groups,group A(sham operation group),group B(myocardial infarction+desflurane and preconditioning group),group C(myocardial infarction group),group D(myocardial infarction+STAT3 activation+desflurane preconditioning group),15 rats in each group.The differences of myocardial infarct size,left ventricular systolic pressure and diastolic blood pressure were detected in each group.Western blotting was used to detect the difference between signal transduction and activators of transduction-3(STAT3)and its phosphorylation level.Results The area of myocardial infarction in the four groups was 0%,(32.7±1.4)%,(58.1±2.7)% and(51.1±1.8)%,respectively.The myocardial infarct size of group C was the largest,followed by group D and group B.The area in group C was significantly higher than that in group B and group D(P<0.05,P<0.01).After the formation of coronary artery occlusion,the systolic and diastolic blood pressures of the four groups were(98±6),(96±8),(76±4),(84±3)mmHg,and(71±3),(73±3),(55±4),(64±2)mmHg,rats in the group C had the lowest systolic and diastolic blood pressure,followed by group D(P<0.05),there was no significant difference between group C and group A.The expression of STAT3 and p-STAT3 was the highest in group C,followed by group D and group B.The expression of STAT3 and p-STAT3 in group C was significantly higher than that in the group B and group D(all P<0.01).Conclusion Desflurane preconditioning has a protective effect on myocardial infarction in rats,and its mechanism may be related to STAT3 and its phosphorylation level.
引文
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[4] Bonney S,Hughes K,Eckle T.Anesthetic cardioprotection:the role of adenosine[J].Curr Pharm Des,2014,20(36):5690-5695.
[5] Zhang M,Wang X,Wang X,et a1.Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signal in rat septic shock[J].Mol Med Rep,2013,7(4):1291-1299.
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[8] 张正升,张申,吴联合,等.建立大鼠急性心肌梗死模型方法的改良[J].临床心血管病杂志,2017,33(3):264-266.
[9] Murry C E,Jennings R B,Reimer K A,Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
[10] Cho Y J,Kim T K,Hong D M,et al.Effect of desflurane-remifentanil vs.Propofol-remifentanil anesthesia on arterial oxygenation during one-lung ventilation for thoracoscopic surgery:a prospective randomized trial[J].BMC Anesthesiol,2017,17(1):9-13.
[11] Dalal K S,Choudhary M V,Palsania A J,et al.Desflurane for ambulatory anaesthesia:A comparison with sevoflurane for recovery profile and airway responses[J].Indian J Anaesth,2017,61(4):315-320.
[12] Kurhekar P,Vinod K,Jsd K,et al.Randomized comparison of isoflurane versus sevoflurane and desflurane for maintenance of ambulatory anesthesia[J].Anesth Essays Res,2017,11(4):875-880.
[13] 杨英,杨俊,杨简,等.吸入麻醉药对心肌缺血再灌注损伤保护作用的研究进展[J].中国老年学杂志,2017,37(8):2055-2057.
[14] 梁宁,刘玲,陈萍.地氟烷预处理对大鼠离体心脏缺血再灌注损伤的影响及作用机制[J].中国老年学杂志,2017,37(4):791-794.
[15] Xu X,Zheng C,Li N,et al.The decrease of NMDAR subunit expression and NMDAR EPSC in hippocampus by neonatal exposure to desflurane in mice[J].Behav Brain Res,2017,317(11):82-87.
[16] 刘开宇,田海,孙露,等.标准化大鼠心肌梗死模型的制作[J].哈尔滨医科大学学报,2007,41(6):531-534.
[17] Xu R,Zhou S,Yang J,et al.Total intravenous anesthesia produces outcomes superior to those with combined intravenous-inhalation anesthesia for laparoscopic gynecological surgery at high altitude[J].IMR,2017,45(1):246-253.
[18] Suryaprakash S,Chakravarthy M,Muniraju G,et al.Myocardial protection during off pump coronary artery bypass surgery:A comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia[J].Ann Card Anaesth,2013,16(1):4-9.
[19] 李铭扬,桑明,孙晓东,等.阿托伐他汀对大鼠心肌梗死后p38磷酸化及心脏重构的影响[J].华中科技大学学报:医学版,2018,47(3):280-285.
[20] Maxwell M P,Hearse D J,Yellon D M.Species variation in the coronary collateral circulation during regional myocardial ischaemia:A critical determinant of the rate of evolution and extent of myocardial infarction[J].Cardiovasc Res,1987,21(10):737-746.
[2] Bienengraeber M W,Weihrauch D,Kersten J R,et al.Cardioprotection by volatile anesthetics[J].Vascular Pharmacol,2005,42(5/6):243-252.
[3] Krolikowski J G,Bienengraeber M,Weihrauch D,et al.Inhibition of mitochondrial permeability transition enhances isoflurane-induced cardioprotection during early reperfusion:The role of mitochondrial KATP channels[J].Anesth Analg,2005,101(6):1590-1596.
[4] Bonney S,Hughes K,Eckle T.Anesthetic cardioprotection:the role of adenosine[J].Curr Pharm Des,2014,20(36):5690-5695.
[5] Zhang M,Wang X,Wang X,et a1.Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signal in rat septic shock[J].Mol Med Rep,2013,7(4):1291-1299.
[6] Lotz C,Fisslthaler B,Redel A,et al.Activation of adenosine-monophosphate-activated protein kinase abolishes desflurane-induced preconditioning against myocardial infarction in vivo[J].J Cardiothorac Vasc Anesth,2011,25(1):66-71.
[7] Yamada M,Chiba T,Sasabe J,et al.Nasal colivelin treatment ameliorates memory impairment related to Alzheimer's disease[J].Neuropsychopharmacology,2008,33(8):2020-2032.
[8] 张正升,张申,吴联合,等.建立大鼠急性心肌梗死模型方法的改良[J].临床心血管病杂志,2017,33(3):264-266.
[9] Murry C E,Jennings R B,Reimer K A,Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation,1986,74(5):1124-1136.
[10] Cho Y J,Kim T K,Hong D M,et al.Effect of desflurane-remifentanil vs.Propofol-remifentanil anesthesia on arterial oxygenation during one-lung ventilation for thoracoscopic surgery:a prospective randomized trial[J].BMC Anesthesiol,2017,17(1):9-13.
[11] Dalal K S,Choudhary M V,Palsania A J,et al.Desflurane for ambulatory anaesthesia:A comparison with sevoflurane for recovery profile and airway responses[J].Indian J Anaesth,2017,61(4):315-320.
[12] Kurhekar P,Vinod K,Jsd K,et al.Randomized comparison of isoflurane versus sevoflurane and desflurane for maintenance of ambulatory anesthesia[J].Anesth Essays Res,2017,11(4):875-880.
[13] 杨英,杨俊,杨简,等.吸入麻醉药对心肌缺血再灌注损伤保护作用的研究进展[J].中国老年学杂志,2017,37(8):2055-2057.
[14] 梁宁,刘玲,陈萍.地氟烷预处理对大鼠离体心脏缺血再灌注损伤的影响及作用机制[J].中国老年学杂志,2017,37(4):791-794.
[15] Xu X,Zheng C,Li N,et al.The decrease of NMDAR subunit expression and NMDAR EPSC in hippocampus by neonatal exposure to desflurane in mice[J].Behav Brain Res,2017,317(11):82-87.
[16] 刘开宇,田海,孙露,等.标准化大鼠心肌梗死模型的制作[J].哈尔滨医科大学学报,2007,41(6):531-534.
[17] Xu R,Zhou S,Yang J,et al.Total intravenous anesthesia produces outcomes superior to those with combined intravenous-inhalation anesthesia for laparoscopic gynecological surgery at high altitude[J].IMR,2017,45(1):246-253.
[18] Suryaprakash S,Chakravarthy M,Muniraju G,et al.Myocardial protection during off pump coronary artery bypass surgery:A comparison of inhalational anesthesia with sevoflurane or desflurane and total intravenous anesthesia[J].Ann Card Anaesth,2013,16(1):4-9.
[19] 李铭扬,桑明,孙晓东,等.阿托伐他汀对大鼠心肌梗死后p38磷酸化及心脏重构的影响[J].华中科技大学学报:医学版,2018,47(3):280-285.
[20] Maxwell M P,Hearse D J,Yellon D M.Species variation in the coronary collateral circulation during regional myocardial ischaemia:A critical determinant of the rate of evolution and extent of myocardial infarction[J].Cardiovasc Res,1987,21(10):737-746.