缺血性脑损伤与瞬时受体电位M通道的研究进展

缺血性脑血管病是临床常见病、多发病,其发病机制复杂。钙超载在缺血性脑损伤中起重要作用。瞬时受体电位M通道（transient receptor potential melastatin,TRPM）是位于细胞膜上的一类重要的非选择性阳离子通道超家族,对钙离子有较高的通透性,在缺血性脑损伤中起重要作用,对TRPM通道的研究将成为治疗缺血性脑损伤新的靶点。本文就胞内钙离子超载在缺血性脑损伤中的作用、TRPM通道及其参与的缺血性脑损伤的机制予以综述。     

酸敏感离子通道在缺血性脑损伤中的作用

背景 酸敏感离子通道(acid sensing ion channels,ASICs)属于阿米洛利敏感的上皮钠通道/退变素(epithelial Na+ channels/degenerin,ENaC/DEG)超家族中的一员,该通道广泛分布在周围和中枢神经系统.最新研究表明Ca2+敏感的ASIC1a的激活在酸中毒介导、谷氨酸受体非依赖的脑缺血性神经损伤中起重要作用.目的 综述ASICs在缺血性脑损伤中的作用.内容从ASICs的结构、分布、功能特点及其在缺血性脑损伤中的作用进行综述.趋向 ASICs可能为阐述缺血性脑损伤的潜在机制提供依据,并为其临床治疗提供方向和思路.     

阿片类药物的外周镇痛作用

阿片类药物的外周抗伤害和镇痛是通过外周阿片受体起作用。初级感觉神经元内存在着阿片受体，在炎症的条件下，阿片受体合成增加并转运到神经末梢，增强阿片类物质的外周作用。炎症部位的免疫细胞释放多种内源性阿片肽，作用于外周阿片受体产生抗伤害和镇痛作用。阿片肽代谢酶抑制剂也能增强阿片肽的外周作用。阿片类芗外周镇痛的临床研究正在进行。     

NMDA受体介导的缺血性脑损伤机制的研究进展

NMDA受体是目前研究最为深入的兴奋性氨基酸受体之一，其兴奋在神经系统的生理及病理状态下都发挥着重要作用。缺血性脑损伤时，NMDA受体介导的信号转导通路发生了一系列的变化。     

氯胺酮在抗缺血性脑损伤中的应用

兴奋性氨基酸（ＥＡＡ）受体过度兴奋在脑缺血神经元损伤中起重要作用。应用突触后ＥＡＡ受体特异拮抗剂可明显缓解和抑制缺血性脑损伤。氨胺酮是ＮＭＤＡ受体非竞争性拮抗剂。它脂溶性高，能通过血脑屏障，发挥中枢抗ＥＡＡ兴奋性毒性作用，或许可能成为临床治疗缺血性脑损伤的药物这一。     

内源性阿片肽与休克

内源性阿片肽与休克的发生发展有密切关系。本文对内源性阿片肽系统中的脑啡肽、强啡肽、内啡肽以及相应的受体做一较详细的介绍，并对休克与内源性阿片肽之间的关系及拮抗剂的使用做进一步的简述。     

大鼠脊髓创伤后脊髓组织中各种内源性阿片肽含量的动态变化及意义

大鼠脊髓创伤后脊髓组织中各种内源性阿片肽含量的动态变化及意义刘绍文，李明，李炳军，洪新如近年研究表明￣［１］：内源性阿片肽作为内源性、自身损害因子参与了脊髓继发性损伤的发生与发展，为进一步探讨参与脊髓损伤病理过程中的阿片肽及其受体类型，我们应用ＲＩＡ...     

基因芯片技术在缺血性脑损伤研究中的应用

基因芯片技术结合了分子生物学和生物信息学原理，应用高密度微阵列快速大量筛选目的基因，在神经科学研究中逐渐发挥举足轻重的作用。现就其原理及其在缺血性脑损伤研究中的应用作一综述。     

兴奋性氨基酸在脑缺血缺氧性钙内流损伤中的作用

本文较详细地介绍了目前国内外学者关注的兴奋性氨基酸的神经毒性作用及其在缺血缺氧性脑损伤中的作用机理,认为钙内流介导了兴奋性氨基酸递质在缺血缺氧性脑损伤中的毒性作用,且进一步阐明了兴奋性氨基酸递质诱发钙内流的主要途径,总结和探讨了兴奋性氨基酸受体拮抗剂在保护缺血缺氧性脑损伤方面的作用及其今后的发展前景。     

氯胺酮在抗缺血性脑损伤中的应用

兴奋性氨基酸(EAA)受体过度兴奋在脑缺血神经元损伤中起重要作用。应用突触后EAA受体(如NMDA受体)特异拮抗剂可明显缓解和抑制缺血性脑损伤。氯胺酮是NMDA受体非竞争性粘抗剂,它脂溶性高,能通过血脑屏障,发挥中枢抗EAA兴奋性毒性作用,或许可能成为临床治疗缺血性脑损伤的药物之一。     

Relative contribution of endogenous opioids to myocardial ischemic tolerance

BACKGROUND: Opioid preconditioning by exogenous opioids experimentally protects the myocardium against ischemia/reflow injury. Additionally, endogenous opioid peptides released during ischemia also enhance ischemic tolerance. Promiscuous opioid receptor agonists conceal the differential contribution of the mu, delta, and kappa opioid subtypes. This study compared the impact of selective delta and kappa opioid receptor antagonists on postischemic functional and metabolic recovery. Also measured were changing levels of peptides dynorphin B and met-enkephalin during ischemia/reflow injury. MATERIALS AND METHODS: Using the rabbit Langendorff model, the functional recovery of control hearts (following 2 h of global ischemia) was compared to hearts pretreated with delta antagonist NTB (1 microM) or kappa antagonist, nor-BNI (1 microM). Measures included percentage of return of isovolumetric developed pressure (LVDP), myocardial oxygen consumption (MVO(2)) and coronary flow (CF). In additional studies, untreated hearts were harvested at baseline, following ischemia, or following 5 or 45 min of reflow. Tissue concentrations of met-enkephalin and dynorphin B were measured by RIA. RESULTS: After 45 min of reflow, hearts pretreated with either NTB or nor-BNI showed impaired functional recovery by a decrease in LVDP (P < 0.05); however, MVO(2) or CF were unaffected. RIA data shows that baseline levels of both peptides are similar and increase significantly during ischemia, but reflow dynorphin levels drop far below baseline, while met-enkephalin returns to baseline. CONCLUSION: Antagonism of both delta and kappa opioid receptor subtypes equally contributes to impaired left ventricular function, independent of altered perfusion or metabolic rate. Endogenous kappa-receptor agonists may contribute primarily during ischemia or early reflow, since low late reflow dynorphin content did not correlate with altered functional recovery.     

纳洛酮对脑缺血/再灌注损伤保护机制的研究进展

纳洛酮是阿片受体的特异拮抗剂,近年来大量实验证实纳洛酮对脑缺血/再灌注损伤具有保护作用.其作用机制包括以下几条途径:纳洛酮能竞争性阻断内源性阿片肽对神经功能的损害作用,减少自由基的产生、减轻钙超载、逆转神经细胞内Mg2+的下降、逆转兴奋性神经毒性、抑制炎症介质的产生、改善神经元能量代谢、抑制神经元细胞凋亡.现就这一领域内的最新进展作一综述.     

Remifentanil post‐conditioning attenuates cardiac ischemia–reperfusion injury via κ or δ opioid receptor activation

Background: Ischemic pre‐ or post‐conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra‐short‐acting selective μ opioid receptor agonist in clinical use, pre‐conditions the rat heart against ischemia–reperfusion injury. This study investigates whether remifentanil post‐conditioning is also cardioprotective. Methods: Remifentanil post‐conditioning (5‐min infusion at 1, 5, 10 or 20 μg/kg/min) or ischemic post‐conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open‐chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor‐binaltorphimine, naltrindole or CTOP, specific κ, δ and μ opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose–response studies. Results: Both ischemic and remifentanil post‐conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post‐conditioning regimes was prevented by the prior administration of nor‐binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post‐conditioning protects the heart from ischemia–reperfusion injury to a similar extent as of ischemic post‐conditioning. This protection involves κ and δ but not μ opioid receptor activation. This drug has great potential as a clinical post‐conditioning modality as it can be given in large doses without prolonged opioid‐related side effects.     

缺氧适应对缺血缺氧脑组织一氧化氮和内皮素的影响

目的 通过观察急性缺氧适应时脑组织－氧化氮（ＮＯ）和内皮素（ＥＴ）的变化,探讨缺氧适应影响脑缺血缺氧损伤的机制。方法 应用急性重复缺氧模型,观察并测定４次缺氧后及应用ＮＯ底物Ｌ－精氨酸、一氧化氮合酶抑制剂（Ｌ－ＮＡＭＥ）后脑组织ＮＯ、ＥＴ含量和低氧存活时间及缺氧适应对缺血缺氧脑组织ＮＯ、ＥＴ及脑含水量影响。结果 （１）缺氧适应明显延长小鼠在低氧存活时间,且ＮＯ明显增加,Ｌ－ＮＡＭＥ抑制这一改变,Ｅ     

外周和中枢阿片受体诱导心脏预处理保护作用及信号转导机制

前期的研究关于阿片类药物预处理的心肌保护效应,主要集中在心脏上的阿片受体在这种保护效应中的作用及信号机制.然而最新的研究已经发现通过中枢(侧脑室内,鞘内)注射吗啡预处理可以直接激活中枢阿片受体,同样可以模拟经典的缺血预处理(ischemia precondition,IPC)心肌保护效应,并且发现中枢神经系统3种阿片受体均参与介导了这种保护作用.这种保护作用的机制可能与痛觉的干预和神经递质的释放等效应有关.     

谷氨酸转运体与缺血性脑损伤

背景 缺血性脑损伤严重威胁人类的生命健康,谷氨酸损伤在缺血性脑损伤的疾病进展中起重要作用,调控谷氨酸浓度对缺血性脑损伤的治疗具有重要意义.目的 探讨缺血性脑损伤与谷氨酸转运体的关系及多种预处理方法对谷氨酸转运体的影响,寻找一种缺血性脑损伤的治疗方法.内容 综述谷氨酸转运体的亚型、分布、结构和功能以及谷氨酸转运体与缺血性...     

The Many Aspects of Endothelins in Ischemia-Reperfusion Injury: Emergence of a Key Mediator

The endothelins (ETs) are regulatory peptides, distributed in many organ systems and producing potent physiological effects. They are the most powerful vasoconstrictive substances known today. They also act as promitogens. Many data supporting pathophysiological roles for ETs are reported, especially regarding diseases related to the vascular system, such as hypertension, pulmonary hypertension, preeclampsia, ischemic heart diseases, renal failure, subarachnoidal hemorrhage, and cerebral ischemia. The development of drugs blocking ET binding to its receptors (antagonists) and the biosynthesis of ETs (ECE inhibitors) presently attracts great interest in terms of establishing new treatments for diseases in which ETs are believed to be involved. Here we review the evidence supporting a role for ETs in the various etiologies related to ischemia-reperfusion injury, such as is found in heart disease, cerebral ischemia, and organ transplantation.     

吗啡预处理对缺血性心肌保护作用的研究进展

实验研究证实吗啡可以模拟缺血预处理.近年来吗啡预处理的心肌保护作用在在体、离体和心肌细胞3种动物模型都得到实验证实,其保护作用分为两个时相:即时相和延迟相.吗啡预处理的心肌保护作用主要由阿片受体介导,与线粒体KATP通道、诱导型NO合酶和环氧化酶等有关.将来在研究其分子机制的同时也会加强对其临床应用的研究.     

海人藻酸受体及其下游信号通路在脑缺血/再灌注损伤中的作用研究进展

背景缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)的机制十分复杂,其中研究较多的N-甲基-D-天冬氨酸受体（N-methyl-D-aspartate receptor,NMDAR）介导的兴奋毒性假说在临床上受到了严峻的挑战,近来的研究已经开始关注海人藻酸受体( kainate re...     

Experimental vasospasm: Experiences with a canine model and failure of naloxone therapy

Experimental vasospasm was studied in a canine model utilizing subarachnoid injection of autologous blood. Alterations in the size of the basilar artery were noted angiographically. Naloxone, an opioid receptor antagonist, has been reported to have a beneficial effect on neurological dysfunction secondary to cerebral ischemia. No significant change in the diameter of the basilar artery was noted in dogs either with or without spasm when treated with naloxone. We have concluded that naloxone has no detectable vasodilatory effect on the cerebral arteries of dogs.