舒芬太尼预处理对大鼠心肌缺血再灌注损伤的影响

目的探索舒芬太尼预处理对大鼠心肌缺血再灌注损伤的作用。方法健康雄性SD大白鼠50只,随机分为5组。采用结扎左冠状动脉前降支30分钟再灌注90分钟的方法制备心肌缺血再灌注模型。I/R组为缺血再灌注对比组,IPC组为缺血预处理组,SPC组为舒芬太尼预处理组,将其分为三个亚组,低剂量组(LS组0.20μg/kg);中剂量组(MS组2.0μg/kg);高剂量组(HS组5.0μg/kg)。应用Even’s blue-TTC法检测心肌梗死范围,以梗死区心肌重量/缺血区心肌重量(IS/AAR%)来表示。于实验结束时(再灌注末),利用硫代巴比妥酸反应法(TBA)测定MDA浓度,利用黄嘌呤氧化酶法测定SOD活性。结果与1/R组比较,IPC组与SPC三个亚组的心肌梗死面积(IS/AAR)均有降低,其中舒芬太尼预处理组(SPC)三个亚组相互比较中,高剂量(HS)组IS/AAR的降低最为明显。与1/R组比较,IPC组及SPC三个亚组的MDA浓度均有下降,SOD活性均有升高。结论舒芬太尼预处理可减轻大鼠心肌缺血再灌注损伤,减少心肌梗死面积,抑制氧化产物的增加,提高机体的抗氧化能力,且呈剂量依赖性。     

Whole body hyperthermia and preconditioning of the heart: basic concepts,complexity, and potential mechanisms

Whole body hyperthermia (WBH) is a distinctive pathophysiological condition with significant impact on tissue metabolism and organ functions. WBH has been investigated as a promising adjunct therapy to the conventional chemo- or radiotherapy for treating certain types of cancer. Numerous studies have shown that WBH is associated with induction of heat shock proteins (HSPs), which in turn modulate cellular survival or death. A brief period of WBH (40-42°C; 15-20min) can induce delayed protection against lethal endotoxemia as well as various forms of injury in brain, heart, liver, lungs, small intestine, and skeletal muscle. This review article focuses on discussing the WBH-induced myocardial protection against ischemia/reperfusion injury. Most recently, possible involvement of protein kinase C, mitogen-activated protein kinases, nitric oxide, ATP-sensitive potassium channels, and neural peptides in the signal transduction pathways has been demonstrated. On the other hand, whether HSPs or antioxidant enzymes are the primary end-effector of the cardioprotection continues to be a matter of ongoing debates. It has also been recognized that the complex nature of WBH may be the responsible factor for the discordant results among various studies, especially across different animal species or strains, in terms of the time course and potency of WBH-induced cardioprotection. Nevertheless, a better understanding of the WBH-elicited myocardial ischemic resistance may have a wide spectrum of clinical implications as well as insightful inputs into the hyperthermic biology.     

The augmentative effect of repeated heat shock preconditioning on the production of heat shock protein 72 and on ischemic tolerance in rat liver tissue

Objective : Heat shock pretreatment induces heat shock protein (HSP)72 strongly in rat livers and provides the tolerance against subsequent ischemia-reperfusion injury. In this study, the effects of repeated heat shock pretreatment on the production of HSP72 in rat livers and on subsequent ischemic tolerance were investigated. Methods : Rats pretreated with repeated heat shock were compared with those that received a single heat shock pretreatment. The production of HSP72 was analysed using Western-blotting and densitometer. At 48h after heat shock pretreatment, all rats were subjected to warm liver ischemia for 30 or 45min and then reperfused. Survival rate of the animals and liver functions during reperfusion were analysed. Results : The production of HSP72 increased in the repeated heat shock group more than in the single heat shock group. Although there were no significant differences in animal survival or in liver functions after a 30-min ischemia between the single heat shock group and the repeated heat shock group, animal survival and liver functions after a 45-min ischemia were significantly better in the repeated heat shock group. Conclusion : In rats, repetition of heat shock pretreatment augmented the production of HSP72 in liver tissue and protected the liver from ischemia-reperfusion injury.     

缺血预处理脑保护机制研究

脑缺血预处理即给予短暂亚致死量缺血可对随后的长时间致死性缺血损伤产生耐受。各国学者就其机制进行了广泛研究并发现这与受体激活和一系列信号转导有关,涉及阿片受体、一氧化氮、腺苷、丝裂原活化蛋白激酶等信号途径、N-甲基-D-天冬氨酸受体、生长因子、线粒体和核生存蛋白、Toll样受体等。但具体机制尚未完全阐明且还处于动物实验阶段,如何把实验结果应用于临床是今后将要解决的问题。     

外源性三磷酸腺苷-氯化镁预处理对大鼠供肝热缺血损伤的保护作用

目的 观察三磷酸腺苷-氯化镁(ATP-MgCl2)预处理对无心跳大鼠供肝热缺血损伤的保护作用.方法 根据ATP-MgCl2预处理与否及供肝获取前经历的供体心脏停搏时间(即热缺血时间)30min或45min,将实验动物分为4组,即非预处理的30min(N-30min)组和45min(N-45min)组,以及ATP-MgCl2预处理的30min(tN-30min)组和45min(tN-45min)组行原位肝移植,观察存活状况,取材行光学显微镜及电子显微镜检查,移植术后1、3、7d 采集血样检测肝功能.结果 N-30min组和N-45min组的1周存活率分别为50.0%和16.7%,而tN-30min组和tN-45min组的1周存活率分别为83.3%和66.7%,预处理组移植肝脏的病理及肝功能明显好于非预处理组.结论 ATP-MgCl2预处理能够减轻供肝的热缺血损伤,改善肝功能,减轻病理损害,提高大鼠肝移植的存活率.     

Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning

Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.     

地氟醚、七氟醚和异氟醚预处理对缺氧/复氧心肌细胞损害的保护作用

目的　研究地氟醚、七氟醚和异氟醚预处理对心肌细胞缺氧／复氧损害的保护作用。方法　原代培养乳鼠心肌细胞，随机分为对照、单纯缺氧／复氧及 １．５ＭＡＣ地氟醚、七氟醚和异氟醚预处理５组。实验结束测定乳酸脱氢酶（ＬＤＨ）和肌酸激酶（ＣＫ）活性、细胞存活和凋亡率。结果　与对照组比，单纯缺氧／复氧使ＬＤＨ、ＣＫ和细胞凋亡率升高及细胞存活率显著下降（Ｐ＜０．０１）；１．５ＭＡＣ地氟醚、七氟醚和异氟醚预处理显著减轻ＬＤＨ、ＣＫ和细胞凋亡率升高及细胞存活率下降，其中七氟醚减轻作用最强。结论　地氟醚、七氟醚和异氟醚预处理对心肌细胞缺氧／复氧损害有一定的保护作用，七氟醚的保护作用可能更强。     

Cardioprotection by breathing hyperoxic gas—relation to oxygen concentration and exposure time in rats and mice

Objectives: Breathing a hyperoxic gas (≥95% O₂) protects against ischaemia-reperfusion injury in rat and mouse hearts. The present study investigated how oxygen concentration and duration of hyperoxic exposure influenced cardioprotection, and whether hyperoxia might induce delayed cardioprotection (after 24 h). Methods: Animals were kept in normal air or in a hyperoxic environment, and their hearts were isolated and Langendorff-perfused immediately or 24 h thereafter. Global ischaemia was induced for 25 min in rats and 40 min in mice, followed by 60 min of reperfusion. Infarct size was determined by triphenyl tetrazolium chloride staining. Results: In rats exposure to ≥95, 80, and 60%, but not to 40% of oxygen immediately before heart isolation and perfusion improved postischaemic functional recovery. Eighty or more percent of oxygen also reduced infarct size. A preconditioning-like effect could be evoked by 60 or 180 min of hyperoxia, giving both immediate and delayed protection. In the mouse heart protection could be induced by pretreatment for 15 or 30, but not by 60 min with ≥95% oxygen. The protective effect of hyperoxia in mice could be evoked in the immediate model only. Conclusions: Hyperoxia protects the isolated rat and mouse heart against ischaemia-reperfusion injury, but some species-different responses exist. The protection depends on both oxygen concentration in inspired air, and duration of hyperoxic exposure.     

异氟醚麻醉对内毒素诱导的大鼠急性肺损伤的预处理效应

目的：探讨异氟醚醉对内毒素诱导的大鼠急性肺损伤的预处理效应，方法：内毒素经股静脉注射Wistar大鼠复制急性肺损伤模型。动物分为：对照组（C组）、单纯异氟醚预处理组（SIso组）内毒素（LSP组）2小时，4小时、8小时组异氟醚预处理＋内毒素（Iso＋LPS组）2小时、4小时、8小时组，观察大体标本，组织病理、肺泡灌洗液中性粒细胞比，蛋白含量，肺湿／干重比，肺血管通透性。结果：LPS组、Iso＋LPS组肺泡灌洗液中中性粒细胞比，蛋白含量均较Ｃ组和SIso组显著增加（P＜0．01）Iso＋LPS组肺泡灌洗液中中性粒细胞比，蛋白含量与LPS组比没有显著差异（P＞0．05）。LPS组和Iso＋LPS组肺湿／干重比、肺血管通透性显著高于C组和SIso组（P＜0．01），而LPS组和Iso＋LPS组两组间无显著差异（P＞0．05）。结论：内毒素可引起严重的急性肺损伤，而异氟醚麻醉对内毒素诱导的急性肺损伤的预处理效应不明显。     

预处理对CO_2气腹致大鼠肝脏损伤的影响

目的探讨预处理对CO2气腹所致肝脏损伤的影响。方法 SD大鼠24只,随机分为3组,每组8只:假气腹组(C组)、气腹组(P组)和预处理-气腹组(PP组)。P组闭合法建立CO2气腹,腹压为15mmHg,维持90min后解除气腹,PP组预处理为5min充气和5min放气,反复两次后建立气腹,维持90min后解除气腹。C组不建立气腹,麻醉时间同PP组。解除气腹后60min取血测定血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)、丙二醛(MDA)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平,光镜观察肝组织病理学变化,进行损伤程度评分。结果与C组比较,P组、PP组血清ALT、AST、MDA、TNF-α、IL-6水平显著增加(P<0.05),SOD显著降低(P<0.05);与P组比较,PP组ALT、AST、MDA、TNF-α、IL-6水平显著降低(P<0.05),SOD显著增加(P<0.05);但3组间肝组织病理损伤评分差异无统计学意义(P>0.05)。结论预处理能减轻CO2气腹所致肝脏损伤,机制可能与减轻氧自由基导致的组织脂质过氧化反应、抑制TNF-α、IL-6释放有关。