二氮嗪对黄疸大鼠肝脏缺血再灌注损伤的影响

目的：研究二氮嗪对梗阻性黄疸肝脏的缺血再灌注损伤是否有保护作用。方法：采用胆总管结扎法制作梗阻性黄疸模型，雄性S—D大鼠60只，分5组：缺血再灌注损伤组（对照组），缺血30min和再灌注120min；GSH活性氧（清除剂）处理组，缺血再灌注前10min静脉注射GSH50mg／kg；二氮嗪预处理组（A、B、C）缺血再灌注前10min分别静脉注射1mg／kg、5mg／kg、10mg／kg。结果：与对照组相比，二氮嗪预处理各组血清中ALT、AST、LDH含量，细胞内MDA含量和SOD活性，肝细胞凋亡指数差异无显著性（P〉0．05），而GSH组与对照组相比，各组血清中ALT、AST、LDH含量，细胞内MDA含量和SOD活性，肝细胞凋亡指数差别具有显著性（P〈0．05）。结论：二氮嗪预处理对大鼠梗阻性黄疸肝脏缺血30min再灌注120min无保护作用，GSH预处理对大鼠梗阻性黄疸肝脏缺血再灌注损伤能／提供保护作用。     

Short-term ischemia usually used for ischemic preconditioning down-regulates central cannabinoid receptors in the gerbil hippocampus

Transient forebrain ischemia of 5-min duration causes delayed neuronal death (DND) of vulnerable CA1 neurons in the gerbil hippocampus, which can be prevented by preconditioning with a short ischemic stimulus of 2.5-min duration. While a key role of excitatory glutamate receptors for both phenomena has been widely accepted, little is known about the postischemic regulation of central cannabinoid (CB1) receptors. The present study was designed to test whether ischemic preconditioning is associated with specific alterations of protein expression and/or ligand binding of these receptors compared to ischemia severe enough to induce DND. Gerbils were subjected to either a 5-min ischemic period resulting in DND of CA1 neurons, or a 2.5-min period of ischemia usually used for preconditioning. Postischemic hippocampal CB1 receptor protein expression was investigated immunohistochemically, while postischemic ligand binding of [³H]CP 55940 to CB1 receptors was analyzed by quantitative receptor autoradiography in both experimental groups after 24, 48, and 96 h (n=4–5 per time point), respectively, and compared to sham-treated gerbils (n=10). Short-term ischemia of 2.5-min duration caused a transient reduction of hippocampal CB1 receptor protein expression, while receptor binding density was permanently decreased. In contrast, 5-min ischemia did not alter protein expression or ligand binding up to 48 h. Based on these data, postischemic down-regulation of hippocampal CB1 receptors, specifically seen after short-term ischemia usually used for preconditioning, may participate in the mechanisms of endogenous postischemic neuroprotection.The first two authors contributed equally     

Unraveling the mysteries of classical preconditioning

Nearly two decades have passed since the first report about ischemic preconditioning. Although we do not yet know unequivocally what the final effector is, we have learned a lot about the signal transduction pathways that result in protection, and have some good prospects for the final step that results in survival or necrosis of the ischemic myocardium. Many investigators have contributed to our current knowledge. We were heartened to learn that four of our JMCC publications are included in the 20 top-cited papers in the journal's history. It is gratifying that our prior publications have generated some interest and stimulated important debate as documented by the high number of citations by scientists in the bibliographies of their own papers. In this document, we have been asked to reflect on those four papers and comment on where they have led us.     

Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia-reperfusion injury

Trimetazidine (TMZ) affects mitochondrial function during ischemia. Mitochondrial permeability transition is a pivotal event in cardiomyocyte death following acute ischemia. The aim of the present study was to determine whether the anti-ischemic agent TMZ might modulate mitochondrial permeability transition pore (mPTP) opening and limit lethal ischemia-reperfusion injury. Anesthetized NZW rabbits underwent 30 min of coronary artery occlusion followed by 4 hours of reperfusion. Prior to this, they underwent either no intervention (control, C), ischemic preconditioning (PC), or an IV injection of 5 mg kg(-1) TMZ 10 min before ischemia (TMZ). Additional rabbits (Sham group) underwent no ischemia/reperfusion throughout the experiment. Infarct size was assessed by triphenyltetrazolium staining, and apoptosis via measurement of caspase 3 activity. Ca(2+)-induced mPTP opening was assessed in mitochondria isolated from ischemic myocardium. TMZ and PC significantly reduced infarct size that averaged 34 +/- 4% and 21 +/- 4% of the risk region respectively, versus 63 +/- 6% in controls (P<0.005). Caspase 3 activity was reduced in both TMZ and PC groups: 37 +/- 11 and 29 +/- 7 respectively, versus 68 +/- 9 nmol min(-1) mg(-1) mitochondrial protein in controls (P=0.01 versus TMZ and PC). In controls, Ca(2+) load required for mPTP opening averaged 11 +/- 4 microM mg(-1) mitochondrial protein versus 116 +/- 6 in shams (P<0.0001). Pre-treatment by TMZ or PC attenuated this, with Ca(2+) loads averaging 45 +/- 4 and 46 +/- 4 microM mg(-1) mitochondrial proteins, respectively (P<0.005 versus C). These data suggest that TMZ inhibits mPTP opening and protects the rabbit heart from prolonged ischemia-reperfusion injury.     

针灸预处理对缺血再灌注大鼠肌细胞凋亡及C—fos基因调控

目的:探求针灸预处理对心肌缺血再灌注损伤大鼠细胞凋亡及C-fosmRNA的影响。方法:采用针灸预处理组间,针灸预处理与缺血预处理比较,利用大鼠心肌缺血再灌注模型观察,分正常对照组、假手术组、缺血再灌注组、缺血预处理组、手针预处理日一次组、电针预处理日一次组、艾灸预处理日一次组、手针预处理日两次组、电针预处理日两次组、艾灸预处理日两次组、结果:表明针灸预处理使C-fosmRNA增多,使细胞凋亡减少,且针灸预处理日两次组比日一次组和缺血预处理更有效。结论:针灸预处理日两次组更有效预防心肌缺血再灌注损伤大鼠细胞凋亡,进一步证明了中医针灸治未病理论科学价值。     

左-卡尼汀预处理对缺血再灌注大鼠心肌的保护作用

目的 探讨左一卡尼汀（L-CN）预处理对大鼠心肌缺血再灌注损伤（MIRI）的心肌保护作用及其可能的机制。方法 36只Wistar大鼠随机分为3组，每组n=12。左一卡尼汀治疗组（L—CN）：术前给予L-CN200mg·kg^-1·d^-1腹腔注射给药5天；缺血一再灌注组（IR）：术前给予等量生理盐水腹腔注射5天；假手术组（P）：术前处理同IR组。L-CN和IR两组大鼠在心电监护下结扎左前降支（LAD）30min后松开结扎线，恢复心肌血流灌注3h后处死动物，P组除LAD仅穿线不结扎外，所有操作同前两组。（1）三组均于术前和处死动物前从颈动脉抽血观察血浆肌酸激酶、MB同工酶（CK-MB）、丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性。（2）实验结束处死大鼠前留取心肌标本，光镜下观察心肌病理学改变，TUNEL法测定心肌细胞的凋亡指数。结果（1）动物处死前，IR组MDA、CK-MB高于L-CN组（P〈0．01），而SOD低于L-CN组（P〈0．01）。（2）IR组心肌细胞凋亡指数明显高于L-CN组（P〈0．05）。（3）组织形态学观察（HE）：IR组心肌纤维水肿、大部分断裂；L-CN组心肌纤维扭曲，但结构基本完整。结论 L-CN预处理对大鼠MIRI具有一定的保护作用，其机制可能是通过抑制心肌脂质过氧化、减少心肌细胞凋亡。     

Extending pharmacological spectrum of opioids beyond analgesia: multifunctional aspects in different pathophysiological states

Opioids are well known to exert potent central analgesic actions. In recent years, the numerous studies have unfolded the critical role of opioids in the pathophysiology of various diseases as well as in biological phenomenon of therapeutic interest. The endogenous ligands of opioid receptors are derived from three independent genes and their appropriate processing yields the major representative opioid peptides beta-endorphin, met-enkephalin, leu-enkephalin and dynorphin, respectively. These peptides and their derivatives exhibit different affinity and selectivity for the mu-, delta- and kappa-receptors located on the central and the peripheral neurons, neuroendocrine, immune, and mucosal cells and on many other organ systems. The present review article highlights the role of these peptides in central nervous system disorders such as depression, anxiety, epilepsy, and stress; gastrointestinal disorders such as diarrhea, postoperative ileus, ulceration, and irritable bowel syndrome; immune system and related inflammatory disorders such as osteoarthritis and rheumatoid arthritis; and others including respiratory, alcoholism and obesity/binge eating. Furthermore, the key role of opioids in different forms of pre- and post-conditioning including ischemic and pharmacological along with in remote preconditioning has also been described.     

Sevoflurane anesthesia did not affect postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft surgery

Purpose The purpose of this study was to retrospectively examine whether sevoflurane anesthesia had any ameliorative effects on postoperative cognitive dysfunction in patients undergoing coronary artery bypass graft (CABG) surgery. Methods One hundred and nine patients underwent elective CABG surgery at our institution from May 1999 to May 2001. From May 1999 to August 2000, the main anesthetic regime used included a propofol infusion with no volatile anesthetic being administered during the surgery. From September 2000 to May 2001, the main anesthetic regime used was 1.5%–2.0% sevoflurane from the postinduction period until the end of the surgery. All patients underwent a battery of neurological and neuropsychological tests 1 day before and 6 months after the operation. Results The use of sevoflurane did not have any significant effects on the postoperative levels of cognitive dysfunction. In contrast, multiple logistic analysis showed that age [odds ratio (OR), 1.3; P = 0.047], diabetes mellitus (OR, 2.5; P = 0.03), and atherosclerosis of the ascending aorta (OR, 1.4; P = 0.047) appeared to be predictive factors of postoperative cognitive dysfunction. Conclusion This retrospective study showed no relationship between postoperative cognitive dysfunction and the use of sevoflurane.     

心肌缺血预适应和后适应影响因素的研究

急性心肌缺血是危害人类生命的原因之一,尽快恢复血液供应是急性心肌缺血的根本治疗手段,但突然恢复血液灌注会出现再灌注损伤。大量的研究证实,心肌缺血预适应和后适应可以减轻再灌注损伤,但具体机制尚未阐明。研究过程中,动物种属、刺激方案、高血糖、高血脂等很多因素可能会干扰心肌缺血预适应和后适应的研究结果,撰文对这些影响因素予以综述。     

前列腺素E_1(PGE_1)预适应对AMI大鼠模型心脏功能的保护作用

目的:研究前列腺素E1(PGE1)预处理对急性心肌梗死大鼠心脏功能及病理改变的影响.方法:将大鼠分为6组:正常对照组(C组)、急性心肌梗死模型对照组(M组)、小剂量PGE1(25μg-kg-1)预处理早期保护作用组(LE组)及延迟保护作用组(LD组)、大剂量PGE1(150μg-kg-1)预处理早期保护作用组(HE组)及延迟保护作用组(HD组).各组均经静脉分别给与等容积生理盐水及不同剂量的PGE1对大鼠进行预处理.除C组外其余各组分别于预处理后20min和24h腹腔注射(ip)异丙肾上腺素(hop)造成急性心肌梗死.Ip以及Isop 24h后测定左室内压及其微分,测定并计算心电图Ⅱ导联,并对心肌进行病理学检查.结果:模型对照组左室内压的最大上升速率( dp/dt max)、最大下降速率(-dp/dt max)和左室发展压(LVDP)均降至正常对照组的30%左右(P＜0.01),而PGE1预处理各组此三项指标均较模型组显著改善(P＜0.01);模型对照组J/R比值剧烈上升,(与正常对照组比P＜0.01),PGE.预处理各组该比值均显著下降(P＜0.01);模型对照组出现较严重的心肌梗死病理改变,PGE1预处理各组心肌坏死程度均有不同程度的减轻.结论:PGE1预处理具有保护急性心肌梗死后的心脏功能,减轻心肌损伤及坏死病理改变的作用.