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。     

线粒体三磷酸腺苷敏感性钾通道与心肌预适应

近年来大量的研究提示,应用钾通道开放剂(PCOs)与缺血预适应(IPC)同样具有明显的抗心肌缺血再灌注损伤的作用,而线粒体三磷酸腺苷敏感性钾通道(mitoKATP)在其中起着重要的作用,其机制尚未明了,可能与以下三方面有关:减少线粒体Ca2+超载,调节线粒体容量与能量代谢,调节自由基的生成。     

川芎嗪预处理对清醒大鼠心肌缺血再灌注损伤的保护作用

目的 :用心肌缺血预处理的整体动物模型 ,观察川芎嗪预处理对清醒大鼠心肌缺血灌注损伤所致心律失常、心肌梗塞面积、乳酸脱氢酶和磷酸肌酸激酶活性的保护作用。方法 :先将实验动物麻醉 ,在人工呼吸状态下 ,开胸 ,左主动脉下穿线。然后 ,缝合胸腔。术后第 6d ,进行实验。单纯缺血再灌注组 :结扎冠脉 30min ,其后再灌 12 0min ;缺血预处理组 :冠脉结扎 5min ,再灌 5min ;然后 ,再次结扎冠脉 30min ,其后再灌 12 0min ;药物组 :川芎嗪 2 0mg·kg- 1 和 40mg·kg- 1 分别连续静脉给药 5min ;5min后 ,结扎冠脉 30min ,其后再灌 12 0min ;结果 :川芎嗪降低缺血和再灌时间VF和VT的发生 ,其发生率为 37 5 % ;使心肌梗塞面积缩小 ,乳酸脱氢酶和磷酸肌酸激酶的释放减少 ;上述指标与单纯缺血再灌注组相比 ,均有显著性差异。其结果与缺血预处理(冠状结扎 5min ,再灌 5min)对心肌缺血再灌注损伤产生的保护作用一致。结论 :川芎嗪通过预处理途径对清醒大鼠心肌缺血再灌注损伤所致心律失常、心肌梗塞面积、乳酸脱氢酶和磷酸肌酸激酶活性产生保护作用。     

ATP-sensitive potassium channels (K(ATP)) in retina: a key role for delayed ischemic tolerance

The objectives of the present study were to determine the localization of K(ATP) channels in normal retina and to evaluate their potential roles in ischemic preconditioning (IPC) in a rat model of ischemia induced by increased intraocular pressure (IOP). Brown Norway rats were subjected to sublethal 3-, lethal 20- and 40-min ischemia and the functional recovery was evaluated using electroretinography. The time interval between ischemic insults ranged from 1 to 72 h. The effects of K(ATP) channel blockade on IPC protection were studied by treatment with 0.01% glipizide. IPC was mimicked by injection of K(ATP) channel openers of 0.01% (-)cromakalim or 0.01% P1060 72 h before 20-min ischemia. Co-expression of K(ATP) channel subunits Kir6.2/SUR1 was observed in the retinal pigment epithelium, inner segments of photoreceptors, outer plexiform and ganglion cell layers and at the border of the inner nuclear layer. In contrast to a 20- or 40-min ischemia, a 3-min ischemia induced no alteration of the electroretinogram (ERG) and constituted the preconditioning stimulus. An ischemic challenge of 40 min in preconditioned rats induced impairment of retinal function. However, animals preconditioned 24, 48 and 72 h before 20-min ischemia had a significant improvement of the ERG. (-)Cromakalim and P1060 mimicked the effect of IPC. Glipizide significantly suppressed the protective effects of preconditioning. In conclusion, activation of K(ATP) channels plays an important role in the mechanism of preconditioning by enhancing the resistance of the retina against a severe ischemic insult.     

Activation of p44/42 mitogen activated protein kinases in thrombin-induced brain tolerance

BACKGROUND: Our recent studies have shown that prior intracerebral injection of a low dose of thrombin attenuates the brain edema formation that results from either an intracerebral hematoma, an intracerebral injection of a large dose of thrombin or cerebral ischemia. The aim of the current study is to investigate whether thrombin-induced tolerance (thrombin preconditioning; TPC) is associated with activation of p44/42 mitogen activated protein (MAP) kinases. METHODS: This study contained three parts. In the first, rats received an intracerebral infusion of either saline or one unit thrombin (the TPC dose) into the right caudate nucleus. After 1, 3 and 7 days, the rats will be killed and brains used to detect p44/42 MAP kinases activation using Western blot analysis and immunohistochemistry. In the second and third parts, rats received intracerebral infusions of either vehicle, one unit thrombin (TPC) or one unit thrombin and 5 nmol PD 098059. These rats were either killed to detect kinases activation after 24 h or received a second intracerebral infusion of five-unit thrombin 7 days later with brain edema being assessed after a further 24 h. RESULTS: Western blot analysis demonstrated that p44/42 MAP kinases were activated in the ipsilateral basal ganglia after the intracerebral infusion of thrombin one unit. Cells immunoreactive for activated p44/42 MAP kinases were found in the ipsilateral basal ganglia and ipsilateral cortex. PD 098059, a MAP kinase kinase inhibitor, abolished thrombin-induced activation of p44/42 MAP kinases. TPC suppressed thrombin-induced brain edema while PD 098059 blocked this protective effect. The water contents in the ipsilateral basal ganglia 24 h after infusion of thrombin five units were 82.6+/-0.8%, 79.2+/-0.4% and 81.8+/-1.9% in the control, TPC alone and TPC plus PD 098059 groups, respectively. CONCLUSION: Thrombin can activate p44/42 MAP kinases within the brain and the protective effects of thrombin preconditioning on brain edema formation are related to this activation.     

吡那地尔预处理对失血性休克大鼠脏器热休克蛋白70和细胞型磷脂酶A2表达的影响

目的 探讨吡那地尔（Pinacidil)预处理（preconditioning,PC)对失血性休克大鼠保护作用的机制。方法 （1）大鼠90只,随机分为正常组（N组,10只）、对照组（C组,40只）和预处理组（PC组,40只）,PC组大鼠用Pinacidil进行预处理,24h后将对照组和预处理组大鼠复制成失血性休克模型,用Westem blot方法观察不同时相点大鼠心肌组织细胞型磷酯酶A2（cPLA2）的表达变化。（2）大鼠60只,随机分为对照组（C组,30只）和预处理组（PC组,30只）,PC组大鼠用Pinacidil进行方法观察PC对大鼠心肌和肝脏组织热热休克蛋白70（hsp70)表达的影响。结果 （1）PC组心机组织cPLA2的表达较弱,而C组表达很强;（2）C组hsp70表达很弱或检测不到,PC组心肌和肝脏hsp70表达很强,24h达到高峰,48h和72h逐渐减弱。结论 Pinacidil预处理可能通过诱导hsp70过度表达和抑制PLA2的表达保护“休克细胞”,从而保护失血性休克大鼠的心肌和肝脏组织。     

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.     

缺血预处理对犬脊髓损伤及热休克蛋白70表达影响的研究

目的评价缺血预处理对犬脊髓损伤及热休克蛋白70表达的影响。方法41条杂种犬随机分成假手术组6只、预处理组21只、对照组14只。预处理组主动脉阻断6min后开放6min,反复2次,之后阻断35min;对照组主动脉阻断35min。术后进行神经功能评分,检测脊髓组织中热休克蛋白70表达。结果在再灌注后6h、24h预处理组热休克蛋白70于胞质和胞核均有表达,且强于对照组;而且神经功能评分预处理组高于对照组。在再灌注后7d预处理组神经功能评分无明显改变,且仍见热休克蛋白70表达。结论缺血预处理可以增加脊髓的缺血耐受;热休克蛋白70在胞质和胞核中表达可能在缺血耐受中起到一定的作用。     

Ischemia and ischemic tolerance in the brain: an overview

Stroke is the third leading cause of death and the leading cause of adult disability in the United States. This review outlines the pathways that lead to cell death following stroke, and also summarizes the current literature on the phenomenon of ischemic tolerance. Ischemic tolerance is an endogenous neuroprotective mechanism by which neurons are protected from the deleterious effects of brain ischemia that occur during and after stroke. A better understanding of the processes that lead to cell death after stroke and endogenous neuroprotective mechanisms like ischemic tolerance could help in the development of new treatment strategies for this devastating neurological disease.