依达拉奉对大鼠肝脏缺血再灌注时线粒体膜电位的影响

目的 探讨依达拉奉对大鼠肝脏缺血再灌注时线粒体膜电位的影响.方法 成年健康雄性SD大鼠30只,体重250 ～ 300 g,采用随机数字表法,将其随机分为3组(n=10):假手术组(S组)、缺血再灌注组(I/R组)及依达拉奉组(E组),I/R组和E组采用肝脏缺血60 min进行再灌注的方法制备70％肝脏缺血再灌注损伤模型.E组于再灌注前15 min静脉注射依达拉奉3 mg/kg,I/R组给予等容量生理盐水.于再灌注2h时采集静脉血样,测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)的活性;然后处死大鼠,取肝组织,测定肝细胞凋亡情况,计算肝细胞凋亡指数;制备肝组织单细胞悬液,测定线粒体膜电位;光镜下观察肝组织病理学结果.结果 与S组比较,I/R组及E组血清ALT活性、AST活性和肝细胞凋亡指数升高,线粒体膜电位降低(P＜0.05或0.01);与I/R组比较,E组血清ALT活性、AST活性和肝细胞凋亡指数降低,线粒体膜电位升高(P＜0.05).E组肝组织病理学损伤轻于I/R组.结论 依达拉奉可减轻大鼠肝脏缺血再灌注损伤,其机制与升高线粒体膜电位,抑制肝细胞凋亡有关.     

兔肝缺血/再灌注损伤肝组织氧压及线粒体形态观察

目的　观察兔肝缺血 /再灌注损伤不同时相肝组织氧压及线粒体形态变化 ,研究常温下肝脏缺血 /再灌注的损伤及其机制。方法　 4 0只兔随机分为 2组即缺血组和对照组。组织气体分析仪持续测定兔肝组织氧压 (Hepatic tissue oxygeonpressure Ptio2 ) ;电镜观察肝脏病理及线粒体形态改变 ,图像分析仪对线粒体的立体形态计量分析。结果　缺血组兔在肝脏缺血后肝 Ptio2值开始下降 ,再灌注 6 0 min时肝 Ptio2仍未恢复正常 (P<0 .0 5 )。电镜观察发现 :肝缺血 30 min,线粒体肿胀、内质网扩张 ,再灌注 6 0 m in后线粒体肿胀进一步加重 ,部分线粒体破坏 ,结构不清 ,线粒体空泡变性。兔肝缺血再灌注损伤后肝细胞线粒体与对照组相比 ,其比表面减小、平均体积增大 (P<0 .0 5 )。结论　常温下入肝血流阻断可以导致肝脏缺血 /再灌注后肝细胞功能障碍和病理损害。其作用机制与缺血期肝细胞缺氧、再灌注期肝脏微循环障碍和肝细胞线粒体的损伤有关     

蛋白激酶C和线粒体ATP敏感性钾通道在未成熟心肌预处理中的作用

目的探讨蛋白激酶C(PKC)和线粒体三磷酸腺苷敏感性钾通道(mitoKATP)在未成熟心肌预处理保护中的作用。方法采用Langendorff离体心脏灌注模型,30只新生日本长耳大白兔分为5组:缺血/再灌注组(I/R组),心脏缺血预处理组(E1组),蛋白激酶C(PKC)阻滞剂chelerythrine(CLT) 心脏缺血预处理(E2组),mitoKATP阻滞剂5-hydroxydecanoate(5-HD) 心脏缺血预处理(E3组),mitoKATP通道开放剂Diazoxide(Diaz)预处理组(E4组)。以血流动力学、生化指标、心肌超微结构等作为观察指标。结果E1和E4组心功能恢复、心肌含水量优于I/R、E2和E4组(P<0.05),三磷酸腺苷含量、超氧化物歧化酶活性、心肌线粒体Ca2 -ATPase活性、心肌线粒体合成三磷酸腺苷(ATP)的能力优于I/R、E2和E4组(P<0.01),丙二醛含量、血清肌酸激酶和乳酸脱氢酶漏出率、心肌细胞内Ca2 含量、心肌线粒体Ca2 含量低于I/R、E2和E4组(P< 0.01),心肌超微结构损伤较I/R、E2和E4组明显减轻。结论心肌缺血预处理对未成熟心肌具有明显的保护作用,其机制可能是通过PKC的激活和mitoKATP通道的开放起作用。     

不同预处理中线粒体KATP通道开放对未成熟心肌的作用

目的　了解线粒体ATP敏感性钾通道 (mKATP)开放在不同预处理过程中对幼兔心脏的影响 ,并探讨其机制。方法　幼兔 (小于 2 8d) 34只随机分成 5组 ,对照组 (n =8) :平衡 30min后缺血再灌注 ;二氮嗪预处理组 (n =8) :缺血前二氮嗪 ( 10 0 μmol/L)灌注 5min后重碳酸盐缓冲液 (KH液 )冲洗 10min ,St.ThomasⅡ (STH)停跳 ;二氮嗪 + 5 羟葵酸 ( 5 HD)预处理组 (n =5 ) :二氮嗪 ( 10 0 μmol/L)和 5 HD( 10 0 μmol/L)一起灌注 5min ;缺血预处理 (IPC)组 ( n =8) :平衡 15min后全心缺血 5min ,复灌 10min行IPC ,STH停跳 ;IPC + 5 HD组 (n =5 ) :IPC前用 5 HD ( 10 0μmol/L)灌注 5min。采用LangendOrff模型 ,常温 ( 38℃ )缺血 30min ,复灌 45min。 结果　缺血 /再灌注 (I/R)后二氮嗪组的线粒体评分较IPC组 (P <0 .0 5 )和对照组 (P <0 .0 1)低 ,IPC前给予 5 HD后线粒体评分仍较对照组低 (P <0 .0 5 )。二氮嗪组和IPC组左室发展压力 (LVDP)、左室压力上升和下降最大速率 (±dp/dtmax)恢复在多个时间点上均优于对照组 ,心肌组织ATP含量高于对照组 (P <0 .0 1) ,心肌酶较对照组降低 (P <0 .0 1)。结论　二氮嗪预处理能产生与IPC相似的心肌保护作用 ,并且对线粒体的保护效果较IPC好。mKATP通道和细胞膜KATP     

Ro-54864对缺血/再灌注心肌功能和线粒体的保护作用

目的 利用Langendorff离体灌注模型探讨Ro-54864对缺血/再灌注心肌功能和线粒体的保护作用.方法 大鼠心脏上架平衡20min后,随机分为5组.假手术组:持续灌注115min;对照组:续灌10min,缺血25min,复灌60min;Ro(Ro-54864)组:缺血前灌注含0.1μmol/L Ro-54864的K-H液10 min;苍术苷(atractyloside,ATR)组:缺血前灌注含20 μmol/L苍术苷的K-H液10 min;ATR+Ro组:缺血前灌注含20 μmol/L苍术苷和0.1 μmol/L Ro-54864的K-H液10 min.分别在平衡20min、缺血前、复灌15 min、60 min记录左室力学指标.在复灌注末,用氯化三苯基四氮唑染色法(TTC)测定心肌梗死面积百分比;分离浆膜下线粒体,电镜下观察线粒体的形态和结构,并进行评分.结果 再灌注15 min后,Ro组的冠脉流量(CF)和血流动力学指标(LVDP,dp/dtmax,dp/dtmin)明显高于对照组和其它处理组,而ATR组的各指标低于对照组(P＜0.05).与对照组(41%±3%)比较,再灌注末期Ro组(28%±3%)心肌梗死面积明显减少(P＜0.05),而ATR组(51%±2%)的梗死面积明显增大(P＜0.05).Ro组(1.51±0.24)心肌线粒体损伤比对照组(2.21±0.27)明显减轻(P＜0.05),而ATR组(3.23±0.36)线粒体损伤较对照组严重(P＜0.05).ATR+Ro组的各项指标与对照组比较无统计学差异.结论 外周苯二氯(卓)受体(peripheral benzodi azepine receptor,PBR)激动剂Ro-54864能够明显减少缺血心肌的梗死面积,保护线粒体,增加冠脉流量,促进缺血心肌功能恢复.线粒体通透性转换孔开放剂苍术苷减弱Ro-54864的心肌保护作用.     

S-腺苷蛋氨酸对大鼠缺血再灌注肝脏能量代谢的影响

目的研究S-腺苷蛋氨酸(SAM)预处理对大鼠肝脏缺血再灌注损伤线粒体功能的影响。方法54只大鼠按随机数字表法随机均分为对照组、缺血再灌注组(I/R组)和SAM组,SAM组大鼠肝脏在缺血前2h行腹腔注射SAM预处理。3组动物在阻断肝门30min后(对照组仅做分离,不阻断肝门)复流,并于再灌注后0、1和6h抽取下腔静脉血检测ALT及AST,切取肝组织检测线粒体SOD、MDA、ATP及EC,并制备病理切片在电镜下观察线粒体的超微结构。结果再灌注后0、1及6h,I/R组ALT、AST和MDA明显高于对照组(P<0.01),SOD(除0h外)、ATP及EC明显低于对照组(P<0.01);SAM组ALT、AST及MDA(除0h外)明显低于I/R组(P<0.01),SOD(除0h外)、ATP及EC明显高于I/R组(P<0.05,P<0.01)。超微结构观察,I/R组线粒体较对照组有明显的损伤,线粒体数量减少,肿胀明显,嵴模糊不清,基质密度低;而SAM组与I/R组相比损伤程度明显减轻。结论SAM能抑制线粒体脂质过氧化反应,提高ATP的产生,最终提高线粒体的能量代谢水平,有效地减轻肝脏的缺血再灌注损伤。     

右美托咪啶后处理对大鼠离体心脏缺血再灌注时线粒体损伤的影响

目的 探讨右美托咪啶后处理对大鼠离体心脏缺血再灌注时线粒体损伤的影响.方法 健康雌性Wistar大鼠,体重220～250 g,成功制备Langendorff离体灌注模型的40个心脏随机分为5组(n=8):缺血再灌注组(A组)、右美托咪啶10 nmol/L组(B组)、右美托咪啶100 nmol/L组(C组)、线粒体通透性转换孔开放剂苍术苷组(D组)及右美托咪啶联合苍术苷组(E组).离体心脏经K-H液平衡灌注20 min后,采用全心停灌40 min再灌注60 min的方法制备离体心脏缺血再灌注模型.于再灌注即刻B组、C组、D组和E组分别灌注含10 nmol/L右美托咪啶、100 nmol/L右美托咪啶、20μmol/L苍术苷、100 nmol/L右美托咪啶和20 μmol/L苍术苷的K-H液10 min.再灌注结束即刻取心尖组织,分离线粒体,测定SOD、Na+ -K+ -ATP酶、Ca2+-ATP酶活性和MDA和Ca2+含量.结果 与A组比较,B组和C组线粒体SOD、Na+ -K+ -ATP酶和Ca2+ -ATP酶活性升高,MDA和Ca2+含量降低(P＜0.05),D组和E组上述指标比较差异无统计学意义(P＞0.05);与C组比较,D组和E组线粒体SOD、Na+-K+-ATP酶和Ca2+ -ATP酶活性降低,MDA和Ca2+含量升高(P＜0.05),B组上述指标比较差异无统计学意义(P＞0.05).结论 右美托咪啶后处理可减轻大鼠离体心脏缺血再灌注时的线粒体损伤,其机制可能与抑制线粒体通透性转换孔开放有关.     

异丙酚预处理对大鼠离体心脏缺血再灌注时心肌线粒体的影响

目的 探讨异丙酚预处理对大鼠离体心脏缺血再灌注时心肌线粒体的影响.方法 成年雄性SD大鼠60只,体重250～300 g,随机分为5组(n=12):对照组(Con组)、缺血再灌注组(I/R)和不同浓度异丙酚组(P1组、P2组、P3组).采用Langendorpf离体心脏灌注模型,用K-H液平衡20 min后,Con组继续用K-H液灌注130 min;I/R组用K-H液灌注40 min,缺血30 min,再灌注60 min;P1组、P2组、P3组于缺血前分别用含50、100、150 μmol/L异丙酚的K-H液灌注10 min,再用K-H液冲洗10 min,该过程总共进行2次为预处理,预处理后各组处理均同I/R组.记录平衡20 min(基础值)、缺血前即刻、再灌注60 min的心率(HR)、左心室舒张末压(LVEDP)、左心室发展压(LVDP)、左心室压力上升及下降速率最大值(±dP/dtmax)、冠脉流量(CF).于再灌注60 min时测定心肌梗死面积以及线粒体电子传递链Ⅰ复合体活性.结果 与Con组比较,再灌注60 min时I/R组LVEDP升高,HR、LVDP、±dP/dtmax、CF均下降,P2组和P3组LVEDP升高,I/R组和P1组心肌梗死面积增大,I/R组、P1组、P2组和P3组线粒体电子传递链Ⅰ复合体活性降低(P＜0.05);与I/R组比较,P2组及P3组再灌注60 min时LVEDP降低,HR、LVDP、±dP/dtmax、CF均升高,P2组及P3组心肌梗死面积减小,P2组和P3组线粒体电子传递链复合体Ⅰ活性升高(P＜0.05).结论 100、150μmol/L异丙酚预处理通过增加心肌线粒体电子传递链复合体Ⅰ的活性,在一定程度上减轻大鼠心肌缺血再灌注损伤.     

线粒体心磷脂在二氮嗪预处理减轻大鼠离体心脏缺血再灌注损伤中的作用

目的 评价线粒体心磷脂在二氮嗪预处理减轻大鼠离体心脏缺血再灌注损伤中的作用.方法 清洁级SD大鼠72只,体重200～280 g,雌雄各半,随机分为对照组(C组)、缺血再灌注组(I/R组)、二氮嗪预处理组(DZ组)和5-羟葵酸拮抗二氮嗪组(HD组),每组18只.采用Langendorff灌流装置建立大鼠离体心脏缺血再灌注模型,C组平衡灌注20 min,持续灌注100 min;I/R组平衡灌注20 min,持续灌注30 min,缺血40 min,再灌注30 min;DZ组平衡灌注20 min后,依次灌注K-H液15 min、50 μmol/L二氮嗪10 min和K-H液5 min,其余缺血再灌注同I/R组;HD组二氮嗪预处理前给予含5-羟葵酸100 μmol/L K-H液10 min,其余处理同DZ组.各组分别于平衡灌注末(T1)、缺血前即刻(T2)、再灌注末(T3)时随机取6只大鼠,监测心率(HR)、左心室发展压(LVDP)和左心室舒张末压(LVEDP),采用高效液相色谱仪测定心肌线粒体心磷脂含量.结果 与T1,2时比较,各组T3时HR、LVDP降低,LVEDP升高,心肌线粒体心磷脂含量降低(P<0.05);与C组比较,其余3组T3时HR、LVDP降低,LVEDP升高,心肌线粒体心磷脂含量降低(P<0.05);与I/R组比较,DZ组T3时HR、LVDP升高,LVEDP降低,心肌线粒体心磷脂含量升高(P<0.05);与DZ组比较,HD组T3时HR、LVDP降低,LVEDP升高,心肌线粒体心磷脂含量降低(P<0.05).结论 二氮嗪预处理可减轻大鼠离体心脏缺血再灌注损伤,与维持心肌线粒体心磷脂含量有关.     

缺血再灌注时心肌线粒体的变化与保护研究进展

线粒体是真核细胞中重要和独特的细胞器,在细胞凋亡和坏死过程中都至关重要。线粒体功能受损是导致缺血再灌注(I/R)心肌不可逆损伤的重要原因之一。因此,针对线粒体的心肌保护措施受到越来越多的关注。一、线粒体在缺血再灌注过程中的改变1.自由基的产生:在I/R过程中氧自由基的生成主要有两个来源,其一是黄嘌呤氧化酶途径。线粒体呼吸链是自由基的另一来源。Vandenhoek等[1] 在离体心肌的I/R模型中证实线粒体电子转移与自由基的生成有关。氧自由基在线粒体中的产生部位被确认为在辅酶Q(泛醌)。当缺氧抑制呼吸链时,辅酶Q被还原成半泛醌,…     

mito-KATP通道在缺血后处理减轻大鼠肾缺血再灌注损伤中的作用

目的 评价线粒体ATP敏感性钾通道(mito-KATP通道)在缺血后处理减轻大鼠肾缺血再灌注损伤中的作用.方法 健康成年雄性SD大鼠35只,体重250～280 g,随机分为5组(n=7):假手术组(S组)仅分离双侧肾蒂,暴露45 min不夹闭;肾缺血再灌注组(I/R组)夹闭双侧肾蒂缺血45 min,再灌注6 h制备大鼠肾缺血再灌注模型;缺血后处理组(Ipo组)夹闭双侧肾蒂缺血45 min,再灌注10 s,缺血10 s,反复3次,再灌注6 h;mito-KATP通道阻断剂5-羟葵酸+I/R组(5-HD+I/R组)缺血前30 min腹腔注射5-HD 10 mg/kg,余处理同I/R组;缺血后处理+5-HD组(5-HD+Ipo组)缺血前30 min腹腔注射5-HD 10 mg/kg,余处理同Ipo组.于再灌注6 h时采集心脏血样,取肾并分离肾小管上皮细胞,测定血清Cr和BUN的浓度、肾小管上皮细胞线粒体膜电位、细胞内活性氧(ROS)含量和游离Ca2+浓度.结果 与S组比较,I/R组、Ipo组、5-HD+I/R组和5-HD+Ipo组血清Cr和BUN的浓度、肾小管上皮细胞内游离Ca2+浓度和ROS含量升高,线粒体膜电位降低(P＜0.05);与I/R组比较,Ipo组血清Cr和BUN的浓度、肾小管上皮细胞内游离Ca2+浓度和ROS含量降低,线粒体膜电位升高(P＜0.05),5-HD+I/R组和5-HD+Ipo组上述指标差异无统计学意义(P＞0.05);与Ipo组比较,5-HD+I/R组和5-HD+Ipo组血清Cr和BUN浓度、肾小管上皮细胞内游离Ca2+浓度和ROS含量升高,线粒体膜电位降低(P＜0.05).结论 mito-KATP通道的开放参与了缺血后处理减轻大鼠肾缺血再灌注损伤的过程.     

Role of glycogen synthase kinase 3β in protective effect of propofol against hepatic ischemia–reperfusion injury

Background

It was previously reported that propofol, an intravenously administered hypnotic and anesthetic agent, protects organs from ischemia–reperfusion (I/R) injury. However, the underlying mechanisms are largely unknown. Glycogen synthase kinase 3β (GSK-3β) is known to play an important role in the oxidative stress–induced apoptosis. In this study, we investigated the role of GSK-3β and mitochondrial permeability transition pore (MPTP) in the protective effects of propofol against hepatic I/R injury.

Materials and methods

The left and median hepatic artery and the portal vein branches were blocked by no-damage artery clips to create the model of partial ischemia (70%), and liver lobes were subjected to warm ischemia for 30, 60, 90 min, respectively. Reperfusion of 120 min was then initiated by the removal of clamp. The MPTP opening was assessed by measuring mitochondrial large amplitude swelling and mitochondrial membrane potential.

Results

Pretreatment with propofol in conditions of hepatic I/R inhibits the apoptosis of hepatocytes as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells. Importantly, propofol suppressed the mitochondrial GSK-3β by promoting or preserving its phosphorylation at Ser9, thus restraining the opening of MPTP and preventing the mitochondrial swell and mitochondrial membrane potential collapse.

Conclusions

Propofol protects liver from I/R injury by sustaining the mitochondrial function, which is possibly involved with the modulation of MPTP and GSK-3β.     

肝脏缺血后处理的保护作用机制

肝脏缺血后处理是指肝脏在长时间缺血后,在再灌注之前进行一次或数次短暂重复的缺血再灌注,能提高肝脏对长时间缺血的耐受性,减轻缺血再灌注损伤.近几年被证实为一种有效、可控制的新的减轻再灌注损伤的方法.肝脏缺血后处理的保护机制与保护肝窦内皮和肝脏细胞超微结构,减轻活性氧引起的细胞损伤及炎症反应,减轻细胞内及线粒体内钙超载,调控凋亡基因,改变线粒体离子通道开放状态等有关.本文就缺血后处理的机制作一简要综述.     

环孢菌素A逆转利多卡因对七氟醚后处理心肌保护的作用

Objective To study the effects of lidocaine on sevoflurane postconditioning-induced cardioprotection.Methods Ischemic status was kept for 40 rain in isolated perfused rat hearts followed by 1 h of reperfusion.Sevoflurane(3%) was administered at the beginning of reperfusion for 15 rain with or without lidocaine (20 μg/ml) perfusion.The direct mitochondrial permeability transition pore (MPTP) inhibitor Cyclosporin A (CsA,0.2 μmol/L) was co-administered in the presence or absence of lidocaine.LVDP,LVEDP,+dp/dtmax were recorded and infarct size was measured with TTC staining.Results Sevoflurane postconditioning significantly improved the recovery of ischernic myocardial function and decreased the infarct size of rat hearts (P＜0.05),which was abolished by lidocaine perfusion.The inhibition of lidocaine on sevoflurane posteonditioning effect was reversed by CsA.Conclusion Sevoflurane postconditioning effectively protects myocardium against ischemia/reperfusion injury,and higher concentration of lidocaine inhibits this protective effect by opening MPTP.     

缺血后处理对大鼠肝缺血再灌注时肝细胞线粒体膜通透性转换和膜电位的影响

目的 评价缺血后处理对大鼠肝缺血再灌注时肝细胞线粒体膜通透性转换和膜电位(△Ψm)的影响.方法 成年健康雄性SD大鼠40只,体重220～260 g,采用随机数字表法,将其随机分为5组(n=8):假手术组(S组)、苍术苷+假手术组(A+S组)、缺血再灌注组(IR组)、缺血后处理组(IPO组)和苍术苷+缺血后处理组(A+IPO组).采用阻断肝中叶和左叶60 min,恢复血流灌注6 h的方法 建立大鼠肝缺血再灌注模型.S组和A+S组仅游离肝门,不阻断血管;A+S组关腹前静脉注射苍术苷5 mg/kg;IR组制备肝缺血再灌注模型;IPO组于再灌注前行缺血后处理,再灌注1 min,缺血1 min,反复3次;A+IPO组于再灌注前静脉注射苍术苷5 mg/kg.于缺血前即刻和再灌注6 h时,采集左颈静脉血样,测定血清ALT和AST的活性.再灌注6 h时处死大鼠,取肝左叶组织,观察超微结构和细胞凋亡情况,计算凋亡指数,测定细胞色素c(Cyt c)的表达水平、△Ψm和线粒体通透性转换孔(MPTP)活性.结果 与S组比较,A+S组时血清ALT和AST的活性、凋亡指数、Cyt c表达、△Ψm和MPTP活性差异无统计学意义(P＞0.05),IR组、IPO组和A+IPO组再灌注6 h时血清ALT和AST的活性、凋亡指数升高,Cyt c表达上调,△Ψm降低,MPTP活性升高(P＜0.05);与IR组比较,IPO组血清ALT和AST的活性、凋亡指数降低,Cyt c表达下调,△Ψm升高,MPTP活性降低(P＜0.05),肝组织病理学损伤减轻,A+IPO组各指标差异无统计学意义(P＞0.05);与IPO组比较,A+IPO组血清ALT和AST的活性、凋亡指数升高,Cyt c表达上调,△Ψm降低,MPTP活性升高(P＜0.05),肝组织病理学损伤加重.结论 缺血后处理可抑制肝细胞线粒体膜通透性转换,减少线粒体△Ψm的耗散,从而减轻大鼠肝缺血再灌注损伤.

Abstract：

Objective To investigate the effects of ischemic postconditioning on mitochondrial permeability transition and mitochondrial transmembrane potential(△Ψm)following hepatic ischemia-reperfusion(I/R)in rats.Methods Forty male SD rats weighing 220-260 g were randomly divided into 5 groups with 8 animals in each group:sham operation group(group S);atractyloside+sham operation group(group A+S);I/R group;ischemic postconditioning group(group IPO)and atractyloside+ischemic postconditioning group(group A+IPO).The animals were anesthetized with intramuscular injection of atropine 0.05 mg/kg.Hepatic I/R was produced by occlusion of hepatic blood flow for 60 min followed by 6 h reperfusion.In group A+S,atractyloside 5 mg/kg was injected intravenously before abdomen Was closed.In group IPO,the animals were subjected to 3 cycles of 1 min reperfusion interspersed with 1 min hepatic isehemia at the end of 60 min hepatic ischemia.In group A+IPO,atractyloside 5 mg/kg was injected intravenously before reperfusion. Venous blood samples were collected for determination of serum ALT and AST activities immediately before ischemia and at 6 h of reperfusion. The animals were then sacrificed.Their livers were removed for microscopic examination, detection of apoptosis and determination of cytochrome c (Cyt c) expression, △Ψm and mitochonerial permeability transition pore (MPTP)activity. Apoptosis index (AI) was calculated. Results There was no significant difference in serum ALT and AST activities, AI, Cyt c expression, △Ψm and MPTP activity between S and A + S groups (P＞0.05). Compared with group S, serum ALT and AST activities and AI were significantly increased, Cyt c expression was up-regulated, △Ψm was decreased and MPTP activity was increased in groups I/R, IPO and A+IPO(P＜0.05).Compared with group I/R, serum ALT and AST activities and AI were significantly decreased,Cyt c expression was down-regulated, △Ψm was increased and MPTP activity was decreased in group IPO(P＜0.05), while no significant change was found in group A+IPO(P＞0.05).Compared with group IPO,serum ALT and AST activities and AI were significantly increased, Cyt c expression was up-regulated, △Ψm was decreased and MPTP activity was increased in group A + IPO(P＜ 0.05).Microscopic examination showed that hepatic injury was reduced in group IPO compared with group I/R, while aggravated in group A+ IPO compared with group IPO. Conclusion Ischemic postconditioning can protect liver from I/R injury by attenuating the I/R-induced increase in MPTP opening and decrease in △Ψm in rats.     

线粒体通透件转换孔在缺血/再灌注损伤中的作用

背景 线粒体作为“能量工厂”提供细胞生长及代谢所需的三磷酸腺苷（adenosine triphosphate,ATP）,同时也是细胞存活与否的重要信号管理者.线粒体通透性转换孔（mitochondrial permeability transition pore,mPTP）是横跨线粒体内外膜之间的允许相对分子质量1.5 kD以下的分子自由通过的孔道.在脑缺血/再灌注（ischemia/reperfusion,I/R）损伤中,线粒体是研究的焦点,而mPTP作为线粒体的门户更是影响着线粒体膜电位（mitochondrial membrane potential,△ψm）、线粒体Ca2＋超载及促细胞死亡物质释放等一系列过程. 目的 对mPTP在I/R损伤中可能的作用机制及治疗方法进行综述. 内容 整理和阐述了mPTP的结构、mPTP与I/R损伤的机制和预防与治疗I/R损伤的可能方法. 趋向 随着mPTP在I/R损伤中的作用机制不断被揭示,其将成为治疗I/R损伤的重要靶点.     

Organ protective effects of volatile anesthetics and perioperative outcomes

Anesthetic agents, especially, volatile anesthetics are considered to exert organ toxicity such as nephrotoxicity and hepatotoxicity; however, recent aggressive researches explored the beneficial effects of volatile anesthetics as an organ protectant. Ischemic preconditioning is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the myocardium and brain against prolonged ischemic insult. General anesthesia showed the protection against both ischemic myocardial and brain reperfusion injuries. This phenomenon is called anesthetic preconditioning. Regarding the organ protection, anesthetic preconditioning is one of the useful ways to diverse the organ protective effects not only to heart but also brain. Nowadays, ischemic postconditioning, consisting of repeated brief cycles of ischemia-reperfusion performed immediately after reperfusion following a prolonged ischemic insult, dramatically reduces infarct size in experimental models and such clinical studies are reported. Both preconditioning and postconditioning share the same signal transduction pathway and inhibit the mitochondrial permeability transition (MPT) that leads to either apoptosis or necrosis of myocardium and neuronal cell. Both phenomena look very promising, but we still lack the real evidence for human reserach in terms of the clinical outcome and further analysis is necessary. Neurotoxicities of anesthetic agents are very crucial problems for the patient and they are considered to be due to the activation of IP3 receptor in ER after exposure to volatile anesthetics. Massive release of Ca2+ from ER induces Ca2+ overload leading to mitochondria permeability transition (MPT) and induces apoptosis in the brain or aggravates the neurodegenerative disease. Susceptible mechanisms and beneficial treatment for the toxicity of general anesthesia is considered as a critical subject to discuss and challenge to solve for our future.     

The influence of B-cell lymphoma 2 protein, an antiapoptotic regulator of mitochondrial permeability transition, on isoflurane-induced and ischemic postconditioning in rabbits

Brief exposure to isoflurane or repetitive, transient ischemia during early reperfusion after prolonged coronary artery occlusion protects against myocardial infarction by inhibiting the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP during delayed ischemic preconditioning occurred concomitant with enhanced expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2). We tested the hypothesis that Bcl-2 mediates myocardial protection by isoflurane or brief ischemic episodes during reperfusion in rabbits (n = 91) subjected to a 30-min left anterior descending coronary artery occlusion followed by 3 h reperfusion. Rabbits received 0.9% saline, isoflurane (0.5 or 1.0 minimum alveolar concentration, MAC) administered for 3 min before and 2 min after reperfusion, 3 cycles of postconditioning ischemia (10 or 20 s each) during early reperfusion, 0.5 MAC isoflurane plus 3 cycles of postconditioning ischemia (10 s), or the direct mPTP inhibitor cyclosporin A (CsA, 10 mg/kg) in the presence or absence of the selective Bcl-2 inhibitor HA14-1 (2 mg/kg, i.p.). Isoflurane (1.0, but not 0.5, MAC) and postconditioning ischemia (20 s but not 10 s) significantly (P < 0.05) reduced infarct size (mean +/- sd, 21% +/- 4%, 43% +/- 7%, 19% +/- 7%, and 39% +/- 11%, respectively, of left ventricular area at risk) as compared with control (44% +/- 4%). Isoflurane (0.5 MAC) plus 10 s postconditioning ischemia and CsA alone also exerted protection. HA14-1 alone did not affect infarct size nor block protection produced by CsA but abolished reductions in infarct size caused by 1.0 MAC isoflurane, 20 s postconditioning ischemia, and 0.5 MAC isoflurane plus 10 s postconditioning ischemia. The results suggest that Bcl-2 mediates isoflurane-induced and ischemic postconditioning by indirectly modulating mPTP activity in vivo.     

吸入麻醉药后处理心肌保护作用机制的研究进展

背景 吸入麻醉药后处理(inhalational anesthetics postconditioning,APO)是指在缺血后冉灌注早期给予一定浓度吸入麻醉药处理.APO具有心肌保护作用,其作用机制目前尚未完全阐明.目的 对APO心肌保护作用机制的研究进展进行回顾和总结.内容 APO的心肌保护的信号转导机制与缺血后处...     

心肌缺血再灌注损伤的线粒体通透性转换机制

线粒体功能障碍存心肌缺血再灌注（ischema／reperfusion I／R）损伤中占有重要地位．近年研究发现线粒体的功能障碍和线粒体通透性转换孔道（mitochondfial permeability transition pore，mPTP）密切相关，