国际麻醉学与复苏杂志
國際痳醉學與複囌雜誌
국제마취학여복소잡지
INTERNATIONAL JOURNAL OF ANESTHESIOLOGY AND RESUSCITATION
2015年
1期
9-12,30
,共5页
七氟烷%预处理%心肌%缺血/再灌注损伤%自噬%雷帕霉素
七氟烷%預處理%心肌%缺血/再灌註損傷%自噬%雷帕黴素
칠불완%예처리%심기%결혈/재관주손상%자서%뢰파매소
Sevoflrane%Preconditioning%Myocardium%Reperfusion injury%Autophagy%Rapamycin
目的 观察自噬增强剂雷帕霉素(rapamycin,RAPA)对七氟烷预处理离体大鼠心脏缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)保护作用的影响,探讨自噬在七氟烷预处理对心肌I/RI保护中的作用. 方法 36只健康成年雄性Wistar大鼠,体重250 g～280 g,采用随机数字表法分为3组(每组12只):缺血/再灌注(ischemia/reperfusion,I/R)组,七氟烷预处理组(S+I/R组),七氟烷预处理+RAPA组(S+I/R+RAPA组).采用Langendorff灌注装置制备离体心脏I/R模型,缺血30 min、再灌注120 min,记录平衡末及再灌注末的左室舒张末期压(left ventricular diastolic pressure,LVEDP)、左室发展压(left ventricular developed pressure,LVDP)、左心室内压最大上升/下降速率(the maximum rate of increase or decrease of left ventricular pressure,±dp/dtmax)、心率(heart rate,HR).再灌注120 min后,收集冠状动脉流出液测乳酸脱氢酶(lactate dehydrogenase,LDH)活性;取心肌,计算心肌梗死面积百分比.Western blot半定量检测自噬标记物微管相关蛋白1轻链3(microtubule-associated protein 1 light 3,LC3)、RAPA靶蛋白(target of rapamycin,mTOR)及磷酸化mTOR (phosphorylated mTOR,p-mTOR)蛋白表达量. 结果 再灌注末,与I/R组比较,S+I/R组心功能明显改善(P＜0.05),心肌梗死面积[(47±6)％、(29±5)％]、冠状动脉流出液LDH活性[(29±5) U/L、(19±4) U/L]均降低,心肌LC3-Ⅱ表达下调,p-mTOR表达上调(P＜0.05);S+I/R+RAPA组各指标与I/R组比较,差异无统计学意义.与S+I/R组比较,S+I/R+RAPA组心功能各项指标呈损害性变化(P＜0.05)、梗死面积增大[(29±5)％、(46±3)％]、冠状动脉流出液LDH活性[(19±4) U/L、(27±5) U/L]均增加(P＜0.05),LC3-Ⅱ表达水平增加,p-mTOR表达降低. 结论 RAPA能够减弱七氟烷预处理对I/RI产生的保护作用,可能与其降低p-mTOR表达,减弱对自噬的抑制作用有关.
目的 觀察自噬增彊劑雷帕黴素(rapamycin,RAPA)對七氟烷預處理離體大鼠心髒缺血/再灌註損傷(ischemia/reperfusion injury,I/RI)保護作用的影響,探討自噬在七氟烷預處理對心肌I/RI保護中的作用. 方法 36隻健康成年雄性Wistar大鼠,體重250 g～280 g,採用隨機數字錶法分為3組(每組12隻):缺血/再灌註(ischemia/reperfusion,I/R)組,七氟烷預處理組(S+I/R組),七氟烷預處理+RAPA組(S+I/R+RAPA組).採用Langendorff灌註裝置製備離體心髒I/R模型,缺血30 min、再灌註120 min,記錄平衡末及再灌註末的左室舒張末期壓(left ventricular diastolic pressure,LVEDP)、左室髮展壓(left ventricular developed pressure,LVDP)、左心室內壓最大上升/下降速率(the maximum rate of increase or decrease of left ventricular pressure,±dp/dtmax)、心率(heart rate,HR).再灌註120 min後,收集冠狀動脈流齣液測乳痠脫氫酶(lactate dehydrogenase,LDH)活性;取心肌,計算心肌梗死麵積百分比.Western blot半定量檢測自噬標記物微管相關蛋白1輕鏈3(microtubule-associated protein 1 light 3,LC3)、RAPA靶蛋白(target of rapamycin,mTOR)及燐痠化mTOR (phosphorylated mTOR,p-mTOR)蛋白錶達量. 結果 再灌註末,與I/R組比較,S+I/R組心功能明顯改善(P＜0.05),心肌梗死麵積[(47±6)％、(29±5)％]、冠狀動脈流齣液LDH活性[(29±5) U/L、(19±4) U/L]均降低,心肌LC3-Ⅱ錶達下調,p-mTOR錶達上調(P＜0.05);S+I/R+RAPA組各指標與I/R組比較,差異無統計學意義.與S+I/R組比較,S+I/R+RAPA組心功能各項指標呈損害性變化(P＜0.05)、梗死麵積增大[(29±5)％、(46±3)％]、冠狀動脈流齣液LDH活性[(19±4) U/L、(27±5) U/L]均增加(P＜0.05),LC3-Ⅱ錶達水平增加,p-mTOR錶達降低. 結論 RAPA能夠減弱七氟烷預處理對I/RI產生的保護作用,可能與其降低p-mTOR錶達,減弱對自噬的抑製作用有關.
목적 관찰자서증강제뢰파매소(rapamycin,RAPA)대칠불완예처리리체대서심장결혈/재관주손상(ischemia/reperfusion injury,I/RI)보호작용적영향,탐토자서재칠불완예처리대심기I/RI보호중적작용. 방법 36지건강성년웅성Wistar대서,체중250 g～280 g,채용수궤수자표법분위3조(매조12지):결혈/재관주(ischemia/reperfusion,I/R)조,칠불완예처리조(S+I/R조),칠불완예처리+RAPA조(S+I/R+RAPA조).채용Langendorff관주장치제비리체심장I/R모형,결혈30 min、재관주120 min,기록평형말급재관주말적좌실서장말기압(left ventricular diastolic pressure,LVEDP)、좌실발전압(left ventricular developed pressure,LVDP)、좌심실내압최대상승/하강속솔(the maximum rate of increase or decrease of left ventricular pressure,±dp/dtmax)、심솔(heart rate,HR).재관주120 min후,수집관상동맥류출액측유산탈경매(lactate dehydrogenase,LDH)활성;취심기,계산심기경사면적백분비.Western blot반정량검측자서표기물미관상관단백1경련3(microtubule-associated protein 1 light 3,LC3)、RAPA파단백(target of rapamycin,mTOR)급린산화mTOR (phosphorylated mTOR,p-mTOR)단백표체량. 결과 재관주말,여I/R조비교,S+I/R조심공능명현개선(P＜0.05),심기경사면적[(47±6)％、(29±5)％]、관상동맥류출액LDH활성[(29±5) U/L、(19±4) U/L]균강저,심기LC3-Ⅱ표체하조,p-mTOR표체상조(P＜0.05);S+I/R+RAPA조각지표여I/R조비교,차이무통계학의의.여S+I/R조비교,S+I/R+RAPA조심공능각항지표정손해성변화(P＜0.05)、경사면적증대[(29±5)％、(46±3)％]、관상동맥류출액LDH활성[(19±4) U/L、(27±5) U/L]균증가(P＜0.05),LC3-Ⅱ표체수평증가,p-mTOR표체강저. 결론 RAPA능구감약칠불완예처리대I/RI산생적보호작용,가능여기강저p-mTOR표체,감약대자서적억제작용유관.
Objective To study the effects of rapamycin (RAPA) on sevoflurane preconditioning during myocardial ischemia/reperfusion(l/R) in rats.Methods Thirty-six healthy adult male Wistar rats,250 g-280 g,were randomly divided into three groups (n=1 2):group I/R,group sevoflurane preconditioning(group S+I/R),group sevoflurane preconditioning plus RAPA(group S+I/R+RAPA).The hearts were excised and perfused in a langendorff apparatus.The left ventricular diastolic pressure (LVEDP),left ventricular developed pressure (LVDP),the maximum rate of increase or decrease of left ventricular pressure (±dp/dtmax),heart rate (HR) were recorded at 30 min of equilibrium and 120 min of reperfusion respectively.Myocardial infarct size and lactate dehydrogenase(LDH)levels were examined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and enzyme standard method at 120 min of reperfusion.Expressions of microtubule-associated protein 1 light 3 (LC3),target of rapamycin (mTOR),phosphorylated mTOR (p-mTOR) were determined by Western blotting.Results After reperfusion,compared with that in group I/R,the cardiac function in group S+I/R was improved (P＜0.05),the myocardial infarct size [(47±6)％,(29±5)％],LDH levels [(29±5) U/L,(19±4) U/L] and the expressions of LC3-Ⅱ were decreased(P＜0.05),while the expression of p-mTOR increased in group S+I/R(P＜0.05).Compared with that in group S+I/R,the cardiac function in group S+I/R+RAPA was worse(P＜0.05),the myocardial infarct size[(29±5)％,(46±3)％],LDH levels[(19±4) U/L,(27±5) U/L] and the expressions of LC3-Ⅱ were increased(P＜0.05),while the expression of p-mTOR decreased (P＜0.05) in group S +I/R +RAPA (P＜0.05).Conclusions Rapamycin could decrease the protective effective of sevoflurane preconditioning and may be related to p-mTOR and autophagy.
