肾缺血预处理对心脏缺血／再灌注损伤的保护作用

目的：探讨肾缺血预处理对家兔心脏缺血／再灌注（I／R）损伤的影响及意义。方法：32只大耳白家兔随机分为假手术（SO）、心脏I／R、经典缺血预处理（CIPC）及肾缺血预处理（RIPC）4组。观察各组心肌梗塞面积、左室舒缩功能、心脏超微结构及心律失常发生率的变化。结果：CIPC、RIPC组,心肌梗塞面积、再灌性心律失常发生率较I／R组明显降低,左室舒缩功能明显恢复（P＜0.01）,心脏超微结构损伤明显减轻。结论：RIPC可诱导出与CIPC类似的心脏保护效应。     

缺血预处理减轻在体家兔心肌细胞凋亡

对麻醉家兔心肌缺血－再灌注（ｉｓｃｈｅｍｉａ－ｒｅｐｅｒｆｕｓｉｏｎ,ＩＲ）模型上,观察ＩＲ和缺血预处理（ｉｓｃｈｅｍｉｃ ｐｒｅｃｏｎｄｉｔｉｏｎｉｇｎ,ＩＰ）对血流动力学、心外膜电图、心肌梗塞范围、心肌细胞调亡和调亡相关调控基因蛋白（Ｆａｓ、Ｂｃｌ－２、Ｂａｘ等）的影响。所得结果如下：⑴在ＩＲ过程中,动脉血压、心率和心肌耗氧量进行性降低;心外膜电图ＳＴ段在缺血期明显抬高（Ｐ＜０．００１）,再灌     

缺血预处理对缺血/再灌注离体心脏的保护作用

目的：探讨连续多次短暂缺血预处理对缺血/再灌注损伤心肌的保护作用及机制。方法：采用大鼠离体心脏Lan-gendorff灌流模型,观察缺血预处理对心肌缺血/再灌注后不同时间点冠脉流出液中AST、CPK、UDH及冠脉流量,心肌组织中SOD、LPO以及再灌注性心律失常的影响。结果：缺血预处理可以减少缺血/再灌注损伤的心肌冠脉流出液中AST、CPK、LDH的含量,提高心肌SOD活性,降低LPO水平,并且抑制再灌注性心律失常的发生,提高再灌注期间的冠脉流量。结论：缺血预处理对心肌缺血/再灌注损伤具有一定保护作用。     

SMT对大鼠在体心脏缺血-再灌注损伤超微结构的保护作用

目的：研究ＳＭＴ对心脏缺血－再灌注损伤（ＩＲＩ）心肌超微结构的影响。方法：ＳＤ大鼠１８只,体重３２０￣３８０ｇ,随机分为三组：①缺血－再灌注组（ＩＲ）：夹闭冠状动脉左前降支６０ｍｉｎ,松夹２０ｍｉｎ。②缺血－再灌注＋ＳＭＴ组（ＳＭＴ）：再灌注前５ｍｉｎ,股静脉注射ｉＮＯＳ抑制剂Ｓ－ｍｅｔｈｙｌｉｓｏｔｈｉｏｕｒｅａ ｓｕｌｆａｔｅ（ＳＭＴ ５ｍｇ／ｋｇ ｗ）,余同ＩＲ组;③对照组（Ｃ）：暴露心脏后     

缺血预处理对肢体缺血/再灌注时肺损伤的保护作用

目的：观察肢体缺血/再灌注（LI/R）时肺损伤的变化并探讨缺血预处理（IPC）对其保护作用。方法：复制家兔LI/R损伤模型,观察肢体缺血4 h再灌注4 h肺损伤的变化以及采用肢体IPC干预后对肺损伤的影响。从右颈外静脉和左颈总动脉采血,分别代表入肺血和出肺血,检测入、出肺血及肺组织超氧化物歧化酶（SOD）的活性、脂质过氧化物的代谢产物丙二醛（MDA）和一氧化氮（NO）的含量;同时测定肺组织总一氧化氮合酶（tNOS）和诱导型一氧化氮合酶（iNOS）的活性以及肢体IPC对上述指标的影响。结果：与对照组和缺血前比较,LI/R组松夹再灌注4 h入、出肺血及肺组织SOD活性明显降低,MDA和NO含量增高（P〈0.05,P〈0.01）;肺组织tNOS和iNOS活性亦升高,与对照组比较,有统计学意义（P〈0.01）。在缺血前给予IPC组,SOD活性升高,而MDA、NO含量降低,tNOS、iNOS活性也降低（P〈0.01）。相关分析显示MDA与SOD间存在明显负相关（P〈0.01）,而MDA与NO及iNOS呈显著正相关（P〈0.01）。结论：LI/R时并发的急性肺损伤与组织氧化代谢紊乱有关,IPC通过改善LI/R时肺组织氧化与抗氧化之间的平衡,进而增强肺组织的抗氧化能力,对LI/R肺损伤具有保护作用。     

黄鼠与大鼠离体心脏预缺血处理对缺血再灌损伤的保护作用

本文用黄鼠和大鼠离体心脏比较了两种预缺血处理方案对随后缺血再灌损伤的作用。用Ｌａｎｇｅｎｄｏｒｆｆ方法灌流秋季未入眠的达乌尔黄鼠和Ｗｉｓｔａｒ大鼠离体心脏,以冠脉流出液中肌酸激酶（ＣＫ）释放活性、心律失常发生率、心功能恢复等为指标,检验不同预缺血处理时间对随后缺血再灌损伤的影响。标本平衡１０ｍｉｎ后对照组的两种动物经受缺灌１５ｍｉｎ再灌１５ｍｉｎ预缺血处理,接着进行两次缺灌１０ｍｉｎ再灌１０ｍｉｎ     

内皮素—1预处理大鼠心脏Gaq／11和Gia蛋白含量的变化

The present study was undertaken to explore the mechanism of G protein-mediated signal transduction pathway during endothelin-1 (ET-1) pre-treatment and ischemic preconditioning (IP). Rats were divided into four groups: ET-1, IP, ischaemia-reperfusion (IR) and control groups. ET-1 pre-treatment model was prepared by administrating 0.5 nmol/(L.kg) ET-1 into rat left ventricle, whereas IP model was prepared by ligating the left coronary artery for 5 min followed by 30 min reperfusion. All the animals were subjected to 60 min regional ischaemia and 30 min reperfusion alternately and then parameters of ventricular arrhythmia and expression of cardiac Galphaq/11 and Gialpha2 were measured. The results showed that the scores of ventricular arrhythmia decreased significantly in both ET-1 and IP treated groups as compared with IR group. In comparison with control group, Galphaq/11 increased by 77.8% (P<0.05) and 110.6% (P<0.01) in IP and ET-1 group respectively. Gialpha2 showed no significant difference in IP group, while it decreased by 31.0% (P<0.01) in ET-1 group. In conclusion, activation of G alphaq/11 may be related to the protecting mechanism of ET-1 pre-treatment and IP, whereas Gialpha2 may only play a role in ET-1 pre-treatment.     

大鼠肢体缺血预处理对肝缺血/再灌注损伤的保护作用

目的：研究肢体缺血预处理对大鼠肝缺血/再灌注损伤是否具有保护作用。方法：雄性SD大鼠32只,随机分为对照组（S组）;缺血/再灌注组（I/R组）;经典缺血预处理组（IPC组）;肢体缺血预处理组（远端缺血预处理组,RPC组）。S组仅行开腹,不作其他处理;IPC组以肝缺血5min作预处理;RPC组以双后肢缺血5min,反复3次作预处理,2个预处理组及I/R组均行肝缺血1h再灌注3h。取血用于血清谷丙转氨酶（ALT）与血清谷草转氨酶（AST）检测。切取肝组织用于测定湿干比（W/D）、中性粒细胞（PMN）计数及观察显微、超微结构的变化。结果：与I/R组比较,IPC组,RPC组ALT,AST,W/D值,及PMN计数均明显降低（P〈0.01）,肝脏的显微及超微结构损伤减轻。结论：肢体缺血预处理对大鼠肝脏I/R损伤有明显的保护作用,强度与经典缺血预处理相当,其机制可能与抑制肝脏炎症反应、减轻肝脏水肿、改善肝组织微循环有关。     

缺血预处理对肢体缺血／再灌注肾损伤保护作用的机制初探

目的：探讨缺血预处理对肢体缺血／再灌注时肾损伤的保护作用。方法：复制家兔肢体缺血／再灌注（I／R）损伤模型,观察肢体缺血4h再灌注4h后以及应用缺血预处理干预对肾损伤的影响。分别从右颈外静脉、肾动脉和肾静脉取血,代表外周血以及入、出肾血,观察外周血超氧化物歧化酶（SOD）、丙二醛（MDA）及尿素氮（BUN）;同时测定入肾血和出肾血NO、SOD、MDA和肾组织SOD、MDA、诱导型一氧化氮合酶（iNOS）以及缺血预处理对上述指标的影响。结果：与对照组比较,缺血再灌组松夹后4h外周血、入、出肾血及肾组织SOD活性明显降低,MDA含量增高（P〈0．01）;外周血BUN以及入、出肾血NO和肾组织iNOS含量升高（P〈0．01）;在缺血前给予缺血预处理组．SOD活性升高,而MDA、BUN、NO、iNOS含量降低（P〈0．01）。相关分析显示MDA与SOD间存在明显负相关（P〈0．01）．而MDA与NO、BUN间呈显著正相关（P〈0．01）。结论：肢体缺血／再灌注时伴有肾脏氧自由基代谢紊乱,缺血预处理可以增强肾组织的抗氧化能力,对肢体缺血再灌注肾损伤具有保护作用。     

后肢远程缺血预处理对小鼠全脑缺血再灌注的保护作用及机理

目的:探讨肢端远程缺血预处理(limb remote ischemic preconditioning)对小鼠全脑缺血再灌注损伤的保护作用及其机制.方法:36只雄性C57小鼠,随机分为3组,即假手术组、对照组和LRPC预处理组,每组12只,假手术组分离双侧颈总动脉不结扎;对照组分离颈总动脉后结扎双侧颈总动脉,20 min后松线;LRPC组首先暴露双侧股动脉,然后结扎1 min,松开5 min,进行3个循环,最后结扎颈总动脉20min后松线.观察和比较各组小鼠海马神经元形态,MPO及炎性因子IL-1β、TNF-α和IL-10含量的变化.结果:再灌注24 h后,LRPC可明显抑制神经元形态的改变(P＜0.05),减少MPO、IL-1β和TNF-α含量,而增加抗炎因子IL-10的含量.结论:LRPC可显著减轻脑缺血再灌注损伤,可能与其降低海马组织TNF-o,IL-1β的含量,增加IL-10的含量有关.     

The timing of propofol administration affects the effectiveness of remote ischemic preconditioning induced cardioprotection in rats

The cardioprotection of remote ischemic preconditioning (RIPC) is abolished under propofol maintained anesthesia. Transient receptor potential vanilloid 1 (TRPV1) channel is present in the heart, and its activation could induce cardioprotection. Therefore, we tested whether the anesthetic propofol administration phase interfered with the RIPC-induced cardioprotection, and RIPC-induced cardioprotection via the cardiac TRPV1 channel. Male Sprague-Dawley rats were subjected to myocardial 30 minutes of ischemia followed by 2 hours of reperfusion. RIPC consisted of three cycles of 5-minute ischemia/reperfusion applied to a hindlimb. Propofol infusion at 12 mg/kg/h was commenced either at 10 minutes before the start of RIPC in the P-pre + RIPC group, or immediately after myocardial ischemia at the onset of reperfusion (P-post + RIPC) while performing RIPC. These two propofol infusion regimes were applied to another two grou bs without RIPC (P-pre and P-post groups). Infarct size (IS) was assessed by triphenyltetrazolium staining. Heart TRPV1 expression was detected by Western blot and immunofluorescence. RIPC significantly reduced myocardial IS compared with the control group (36.7 ± 3% versus 57.2 ± 4%; P < .01). When propofol was started before RIPC, the IS sparing effect of RIPC was completely abolished. However, propofol infusion starting immediately after myocardial ischemia did not affect RIPC-induced cardioprotection. TRPV1 expression significant increase after RIPC, then propofol inhibited the TRPV1 activation of RIPC if given before RIPC but not after. Our results suggest that the timing of propofol administration is critical to preserve the cardioprotection of RIPC. Propofol might cancel RIPC-induced cardioprotection via the cardiac TRPV1 receptor.     

血红素氧合酶-1在离体大鼠心肌缺血预适应中的作用

目的:分别观察给予HO-1诱导剂和抑制剂对心肌相对缺血再灌注损伤和缺血预适应的影响,探讨HO-1在缺血预适应中的作用.方法:实验动物随机分为对照组(CN)、缺血/再灌损伤组(I/R)、缺血预适应 缺血/再灌损伤组(PC)、HO-1诱导剂 缺血/再灌损伤组(HM)、HO-1抑制剂 缺血预适应组(ZP).心肌缺血/再灌损伤采用相对缺血/再灌损伤模型,缺血预适应则为相对缺血5min恢复5min,反复2次.测定心功能、MDA及HO-1活性变化.结果:HM组HO-1活性升高,心功能恢复率均显著高于IR组(P＜0.01),MDA含量显著低于IR组(P＜0.05).ZP组活性降低,心功能恢复率显著低于PC组(P＜0.05),MDA含量显著高于PC组(P＜0 05).结论:HO-1是缺血预适应释放的内源性活性物质之一.     

缺血预处理对缺血再灌注后兔脊髓磷酸腺苷代谢的影响

目的：研究缺血参处理对缺血再灌注后兔脊髓磷酸腺苷代谢的影响。方法：往置入腹主动脉的Swan-Ganz导管气囊内注气造成兔腰髓缺血模型。将实验兔分为假手术组、缺血组和预处理组。应用反相高效液相色谱方法（reverse phase HPLC),对缺血再灌注后不同时间点腰髓组织中磷酸腺苷（ATP、ADP、AMP）的含量进行检测。结果：和假手术组相比,缺血组兔再灌后各时间点腰髓组织ATP含量有明显下降（P＜0．01）。与缺血组相应时间点相比,预处理组兔再灌注后腰髓组织ATP含量明显提高（P＜0．01）。结论：缺血预处理显著提高缺血再灌注后兔脊髓组织ATP含量,这可能是缺血预处理对脊髓缺血再灌注损伤产生保护作用的机制之一。     

Absence of ischemic preconditioning protection in diabetic sheep hearts: Role of sarcolemmal KATP channel dysfunction

Sarcolemmal ATP-sensitive potassium (KATP) channels have been mentioned to participate in preconditioning protection. Since these channels are altered in diabetes, it would be possible that preconditioning does not develop in diabetic (D) hearts. The purpose of this study was to assess whether early (EP) and late (LP) ischemic preconditioning protect diabetic hearts against stunning in a conscious diabetic sheep model and whether diabetes might have altered KATP channel functioning. Sheep received alloxan monohydrate (1 g) and were ascribed to three experimental groups: control (DC, 12 min of ischemia (I) followed by 2 h of reperfusion (R)), early preconditioning (DEP, six 5 min I – 5 min R periods were performed before the 12 min I) and late preconditioning (DLP, same as DEP except that the preconditioning stimulus was performed 24 h before the 12 min I). Regional mechanics during reperfusion was evaluated as the percent recovery of wall thickening fraction (%WTH) expressed as percentage of basal values (100%) and KATP behaviour was indirectly assessed by monophasic action potential duration (MAPD) and sensitivity to glibenclamide blockade (0.1 and 0.4 mg/Kg). The results were compared to those obtained in normal (N) sheep. EP and LP protected against stunning in normal sheep (%WTH: NC = 63 ± 3.7, NLP = 80 ± 5**, NEP equals; 78 ± 3*, *p < 0.05 and **p < 0.01 against NC) whereas contrary results occurred in diabetic ones, where DLP (%WTH = 60 ± 4) afforded a similar recovery to DC (%WTH = 54 ± 5) and DEP surprisingly worsened instead of improving mechanical function (%WTH = 38 ± 6, p < 0.01 against DC). KATP channel behaviour appeared altered in diabetic hearts as shown by MAPD during ischemia in normal sheep (153 ± 9 msec) compared to diabetic ones (128 ± 11 msec, p < 0.05) and by the sensitivity to glibenclamide (while 0.4 mg/Kg blocked action potential shortening in normal and diabetic animals, 0.1 mg/Kg completely blocked KATP in diabetic but not in normal hearts, p ( 0.05). A sarcolemmal KATP channel dysfunction might afford a primary approach to explain the absence of ischemic preconditioning protection against stunning in diabetic sheep.     

缺血后处理内源性心脏保护的研究进展

再灌注疗法是临床治疗心肌缺血最有效的措施,但会引起再灌注损伤,调动机体内源性保护机制可以减轻再灌注损伤,保护缺血心肌。缺血预处理（ischemic preconditioning,IPC）和后处理（ischemic postconditioning,I-postC）是缺血心脏有效的内源性保护现象,可以减轻缺血再灌注（ischemia／reperfusion,I／R）后心肌坏死与心肌功能障碍,减少恶性心律失常的发生。内源性心脏保护的机制主要是通过诱导触发因子释放,经多条细胞内信号转导途径的介导,作用于多种效应器,影响氧自由基产生、钙超载等I／R损伤的关键环节而发挥心肌细胞保护作用。特别是可以在缺血后实施的I-postC具有良好的临床应用前景。本文以I-postC为重点综述内源性心脏保护作用、机制及其临床应用现状。     

大鼠肢体预缺血减小心肌缺血-再灌注后的梗塞范围

在氨基甲酸乙酯麻醉大鼠上观察肢体预缺血(limb ischemic preconditioning,LIP)对缺血-再灌注(ischemia—reperfusion,IR)心肌的影响,旨在探讨LIP对IR心肌有无保护效应,并明确腺苷和神经通路是否参与此效应。所得结果如下:(1)在心脏缺血30 min和再灌注120 min过程中,梗塞心肌占缺血心肌的51.48±0.82％。(2)LIP时心肌梗塞范围为35.14±0.88％,较单纯心肌缺血-再灌注时显著减小(P<0.01),表明LIP对心肌有保护作用。(3)事先切断股神经可取消LIP的保护效应。(4)股动脉内局部给予腺苷(10nmol/kg),可模拟LIP对心肌的保护作用;心肌梗塞范围是37.28±1.68％,而股静脉内注射同等剂量腺苷则无保护作用。(5)股动脉内预先应用腺苷A.受体拈抗剂8-环戊-1,3-二丙基嘌呤(DPCPX)(32 nmol/kg)可部分阻断LIP诱发的心肌保护效应。以上结果表明,肢体短暂预缺血可减小心肌缺血-再灌注后的梗塞范围,而局部释放的腺苷和由此所激活的相关的神经通路在LIP的心肌保护中起重要作用。     

肢体缺血预处理减轻大鼠海马缺血/再灌注损伤

目的:探讨肢体缺血预处理(LIP)对大鼠全脑缺血/再灌注损伤的影响.方法: 36只大鼠椎动脉凝闭后随机分为假手术(Control)组、脑缺血组、肢体缺血组、LIP 0 d组(LIP后即刻行脑缺血)、LIP 1 d组(LIP后1 d行脑缺血)和LIP 2 d组(LIP后2 d行脑缺血).重复夹闭大鼠双侧股动脉3次(每次10 min,间隔10 min)作为LIP,夹闭颈总动脉进行全脑缺血8 min后再灌注.硫堇染色观察海马CA1区组织学分级及锥体神经元密度以判断海马损伤程度.结果:脑缺血组海马CA1区锥体神经元损伤严重,与Control组比较,组织学分级明显升高,神经元密度明显降低(P<0.01).LIP 0 d组海马CA1区神经元损伤较脑缺血组明显减轻,组织学分级明显降低,神经元密度明显升高(P<0.01).而LIP 1 d组和LIP 2 d组大鼠海马CA1区锥体细胞缺失较多,仍有明显的组织损伤.结论:LIP可减轻随后立即发生的脑缺血/再灌注损伤,但对间隔1 d后的脑缺血/再灌注损伤无显著对抗作用.     

缺血预处理合并低温及晶体停搏液对兔未成熟心肌的保护作用

本文拟探讨缺血预处理(ischemic preconditioning,IP)合并低温及晶体停搏液对幼兔的离体心脏是否具有心肌保护作用.采用Langendorff离体心脏灌注模型,灌注液为Krebs-Henseleit液(K-H液).取3～4周龄幼兔心脏,在第一部分实验中分为Con、IP1、IP2、IP3组(n=6),分别给予0、1、2、3次IP,其后各组心脏均在20℃低温下停灌2 h,37℃常温下再灌注30 min.在第二部分实验中分为SConI、SCon2、SCon3、SIPl、SIP2、SIP3组(n=8),其中SIPl、SIP2、SIP3组给予2次IP后灌注St.Tho-mas Ⅱ晶体停搏液(CCS)使心脏停搏,然后分别使心脏在32℃、25℃、20℃下停灌30、90和120min,其后各组均在37℃再灌注30 min.SConl,SCon2,SCon3三组则不给予IP,继续灌注20min后灌注CCS使心脏停搏,然后分别在32℃、25℃、20℃下停灌30、90和120 min,其后各组均在37℃再灌注30 min.以Maclab/4 s生理实验系统记录平衡末、缺血前、再灌注后1、3、5、10、20、30 min时心率(HR)、左心室发展压(LVDP)以及左心室内压上升及下降最大速率(±dp/dtmax),测定再灌注末心肌组织中ATP和丙二醛(MDA)的含量,以及超氧化物歧化酶(SOD)的活性.在20℃低温停灌且停灌期间不给予CCS时,再灌注末IP2组LVDP×HR、+dp/dtmax和-dp/dtmax的恢复率分别为96%±21%、101%±19%和84%±15%,显著高于Con组和IP3组(P＜0.01,P＜0.05);心肌组织的ATP含量亦高于Con组(P＜0.01).在不同低温停灌且停灌期间给予CCS时,再灌注末SIP1、SIP2组的LVDP×HR、+dp/dtmax分别恢复到87%±14%、99%±26%(P＜0.05,vs SConl group)和87%±16%、102%±20%(P＜0.05,vs SCon2 group);心肌组织的ATP含量均分别显著高于SCon1组和SCon2组(P＜0.05),心肌组织MDA含量亦分别低于SCon1组和SCon2组(P＜0.05).上述结果提示,IP对在20℃低温停灌的兔未成熟心脏具有一定的心肌保护作用,2次IP的保护效应优于1次或3次IP.在停灌期间应用CCS,IP的心肌保护作用随停灌期间低温程度的升高而减弱.     

Involvement of the mitochondrial calcium uniporter in cardioprotection by ischemic preconditioning

The objective of the present study was to determine whether the mitochondrial calcium uniporter plays a role in the cardioprotection induced by ischemic preconditioning (IPC). Isolated rat hearts were subjected to 30 min of regional ischemia by ligation of the left anterior descending artery followed by 120 min of reperfusion. IPC was achieved by two 5-min periods of global ischemia separated by 5 min of reperfusion. IPC reduced the infarct size and lactate dehydrogenase release in coronary effluent, which was associated with improved recovery of left ventricular contractility. Treatment with ruthenium red (RR, 5 μM), an inhibitor of the uniporter, or with Ru360 (10 μM), a highly specific uniporter inhibitor, provided cardioprotective effects like those of IPC. The cardioprotection induced by IPC was abolished by spermine (20 μM), an activator of the uniporter. Cyclosporin A (CsA, 0.2 μM), an inhibitor of the mitochondrial permeability transition pore, reversed the effects caused by spermine. In mitochondria isolated from untreated hearts, both Ru360 (10 μM) and RR (1 μM) decreased pore opening, while spermine (20 μM) increased pore opening which was blocked by CsA (0.2 μM). In mitochondria from preconditioned hearts, the opening of the pore was inhibited, but this inhibition did not occur in the mitochondria from hearts treated with IPC plus spermine. These results indicate that the mitochondrial calcium uniporter is involved in the cardioprotection conferred by ischemic preconditioning.