Rho激酶抑制剂在神经退化性疾病上的应用

Rho激酶,又称Rho相关的卷曲蛋白激酶,是一类丝氨酸/苏氨酸蛋白激酶,被发现为小G蛋白Rho的下游作用底物。由于Rho激酶活性涉及神经细胞的功能,而且越来越多的研究表明抑制Rho激酶的活性在数种神经退行性疾病包括帕金森病、阿尔茨海默病、亨廷顿病、多发性硬化症,和肌萎缩性侧索硬化症等的实验模式中都有明显的效果。因此,Rho激酶已成为针对治疗神经性退化性疾病的一个热门标靶蛋白。本文探讨Rho激酶抑制剂在神经退化性疾病上的应用及发展,使神经退行性疾病能进一步提升治疗和在应用上的水平。     

Rho与中枢神经系统轴突再生

Rho是小分子质量GTP酶Rho家族成员,在细胞的一些信号转导途径中起着分子开关的作用.Rho能通过作用于肌动蛋白骨架系统引起轴突生长锥塌陷,从而抑制轴突生长.研究表明,Nogo-A、MAG、OMgp等髓鞘源性的轴突再生抑制分子均可通过激活Rho介导的信号转导途径抑制轴突再生.     

Rho激酶抑制剂Y-27632促进大鼠成骨细胞早期分化

已知Rho激酶抑制剂可调控细胞骨架重建,激活相关转录因子,进而促进细胞分化。然而,关于Rho激酶抑制剂对细胞骨架和成骨细胞分化的影响及两者之间关系尚未见报道。本研究旨在阐明Rho激酶抑制剂Y 27632调控细胞骨架重建,促进成骨分化。取新生SD大鼠头盖骨组织体外培养细胞传至第3代,给予Rho激酶抑制剂Y-27632进行干预。采用罗丹明标记的鬼笔环肽对细胞骨架进行细胞化学染色。结果显示,培养1 d和2 d,Rho激酶抑制剂Y-27632处理的细胞呈现多角形,并伴有部分伪足形成。细胞培养4 d和7 d,Y-27632处理的细胞碱性磷酸酶（alkaline phosphatase, ALP）活性明显增加（P<0.01）。实时定量PCR揭示,加Y-27632处理细胞的骨分化相关基因Runx2、Alp、β-catenin(β-cat)、osteopontin(Opn)的mRNA表达水平均显著高于对照细胞（P<0.05或P<0.01）。以上结果证明,Rho激酶抑制剂Y 27632能够影响大鼠成骨细胞的形态,并有促进其分化作用。本研究为骨代谢疾病及组织工程的研究提供了新的线索和启示。     

法舒地尔对急性心肌梗死大鼠心肌组织中Rho激酶的影响及心肌保护作用(英文)

目的:分析急性心肌梗死(AMI)后大鼠心肌组织Rho激酶表达的变化及心肌细胞凋亡情况,观察法舒地尔对急性心肌梗死(AMI)后大鼠心肌组织Rho激酶表达的影响,探讨法舒地尔对心梗后心肌的保护作用。方法:选取雄性Wistar大鼠,随机分为三组:治疗组、AMI组、假手术组。治疗组及AMI组均结扎左前降支(LAD)制作AMI模型;假手术组只在其LAD下穿线不结扎。治疗组给予法舒地尔5mg/kg,腹腔注射,每日两次;对照组和假手术组给予等量生理盐水。1周后,EvensBlue及NBT双染色确定缺血面积及梗死面积,RT-PCR法测定rho激酶mRNA的表达,DNA断裂的原位末端标记法(T UNEL法)检测缺血区心肌细胞凋亡指数(AI),免疫组化测定凋亡相关蛋白bcl-2及bax表达的变化。结果:1周后,AMI组与假手术组相比,AMI组大鼠Rho激酶mRNA表达增加(P0.01),凋亡相关蛋白bax表达增加(P0.01),bcl-2表达减少(P0.01),AI明显增加(P0.01)。治疗组与AMI组相比,梗死面积显著减小(P0.05),Rho激酶mRNA及bax表达显著减少,AI显著降低,bcl-2表达显著增加(均P0.01)。结论:大鼠AMI后,心肌组织中Rho激酶的表达增加,心肌细胞凋亡指数增加,连续应用法舒地尔1周能有效减少心肌细胞凋亡指数,起到心肌保护的作用。     

慢性低氧高二氧化碳肺动脉高压小鼠肺组织Rho激酶的表达变化

慢性低氧高二氧化碳性肺动脉高压严重威胁着国民身体健康,但其发病机制尚未完全阐明。该研究通过检测正常对照组和慢性低氧高二氧化碳组小鼠右心室肥厚指数(right ven-tricular hypertrophy index,RVHI)、管壁厚度占血管外径的百分比(vessel wall thickness/total vasculardiameter,WT%)和管壁面积占血管总面积的百分比(vessel wall area/total vascular area,WA%),RT-PCR检测肺组织中Rho激酶(ROCK1,ROCK2)基因的表达,Western blot检测肺组织中ROCK1、p-MYPT1(phospho-myosin phosphatase target subunit 1)蛋白的表达,免疫组织化学法观察ROCK1的定位表达,探讨了Rho激酶在慢性低氧高二氧化碳性肺动脉高压形成中的作用。结果发现,慢性低氧高二氧化碳组小鼠RVHI、WT%、WA%值均显著升高(P<0.01),ROCK1、ROCK2基因表达明显增加(ROCK1 P<0.01,ROCK2 P<0.05),ROCK1、p-MYPT1蛋白表达显著增加(P<0.01),ROCK1蛋白表达于肺动脉、肺泡和支气管。以上结果提示,慢性低氧高二氧化碳条件下,小鼠肺组织中Rho激酶表达升高,可能参与了肺动脉高压的形成。     

大鼠骨髓间充质干细胞分化的内皮样细胞促进血管新生及Rho激酶的作用

本文研究大鼠骨髓间充质干细胞分化生成的内皮样细胞(rat bone marrow mesenchymal stem cells-differentiated endothelial like cells,rBMSC-ECs)在血管新生中的作用及Rho激酶(Rho kinase,ROCK)活性抑制的影响。实验建立rBMSC-ECs与主动脉环体外共培养实验模型,设单纯血管环组、血管环与细胞共培养组和HA-1077低、中、高浓度组,HA-1077组在共培养的基础上分别在培养液中加不同浓度(10、30、60mmol/L)的ROCK特异抑制剂HA-1077。结果显示,培养第3天,血管环与细胞共培养组新生微血管数是单纯血管环组的1.3倍(P<0.05);HA-107710、30和60mmol/L组较共培养组分别减少57.70%、64.13%和48.23%(均P<0.01)。第6天,共培养组及HA-1077组rBMSC-ECs数量明显增加,并迁移至血管环周边,新生微血管生长缓慢;HA-1077组新生微血管数较共培养组明显减少。第9天,共培养组新生微血管部分增粗、增厚、延长,部分退化;一些rBMSC-ECs出芽,形成毛细血管...     

Rho小G蛋白相关激酶的结构与功能

Rho小G蛋白家族是Ras超家族成员之一,人类Rho小G蛋白包括20个成员,研究最清楚的有RhoA、Rac1和Cdc42。Rho小G蛋白参与了诸如细胞骨架调节、细胞移动、细胞增殖、细胞周期调控等重要的生物学过程。在这些生物学过程的调节中,Rho小G蛋白的下游效应蛋白质如蛋白激酶（p21-activated kinase,PAK）、ROCK（Rho-kinase）、PKN（protein kinase novel）和MRCK（myotonin-related Cdc42-binding kinase）发挥了不可或缺的作用。迄今研究发现,PAK可调节细胞骨架动力学和细胞运动,另外,PAK通过MAPK（mitogen-activated protein kinases）参与转录、细胞凋亡和幸存通路及细胞周期进程;ROCK与肌动蛋白应力纤维介导黏附复合物的形成及与细胞周期进程的调节有关;哺乳动物的PKN与RhoA/B/C相互作用介导细胞骨架调节;MRCK与细胞骨架重排、细胞核转动、微管组织中心再定位、细胞移动和癌细胞侵袭等有关。该文简要介绍Rho小G蛋白下游激酶PAK、ROCK、PKN和MRCK的结构及其在细胞骨架调节中的功能,重点总结它们在真核细胞周期调控中的作用,尤其是在癌细胞周期进程中所发挥的作用,为寻找癌症治疗的新靶点提供理论依据。     

老年急性脑梗塞患者血清TNF-a和IL-6水平的变化及其临床意义

目的：观察老年急性脑梗塞（ACI）患者血清TNF-a和IL-6水平的变化并探讨其临床意义。方法：选择老年ACI患者53例,观察以上入选患者入院后第7d、第9d和第11d血清TNF-a和IL-6水平的变化。并与26例健康人对照;同时分析53例老年ACI患者血清TNF—a和IL-6水平与患者脑梗塞面积及神经功能缺损评分的Spearman等级相关性。结果：老年ACI患者血清TNF-a和IL-6水平显著高于健康人（P〈0．01）;随着治疗的进展与病情的稳定及恢复,患者血清TNF-a和IL-6水平随之显著下降（P〈0．05）;同时患者血清TNF-a和IL-6水平与病变的严重程度呈正相关性（P〈0．05）;治疗11d后血清TNF—a和IL-6降低量与病变的严重程度呈正相关性（P〈0．05）。结论：在老年ACI患者治疗过程中,应进行血清TNF-a和IL-6水平的动态监测,可提示病变的发生发展并指导临床治疗。     

脑梗塞患者血清hs-CRP、TNF-α、血脂水平的变化及其临床意义

目的:观察脑梗塞患者血清超敏C反应蛋白(hs-CRP)、肿瘤坏死因子(TNF-α)及血脂水平的变化,并探讨其临床意义.方法:选择我院2010年6月～2012年6月收治的86例急性脑梗塞患者(轻型脑梗塞组27例、中型脑梗塞组34例、重型脑梗塞组25例)为实验组和同期40例健康体检者为对照组,检测和比较两组血清超敏C反应蛋白(hs-CRP)、肿瘤坏死因子(TNF-α)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)的水平,并进行相关性分析.结果:与健康对照组比较,实验组血清hs-CRP、TNF-α及TC、TG、LDL-C水平显著升高,而血清HDL-C水平显著降低,差异均具有统计学意义(P＜0.05).与轻型脑梗塞组比较,中、重型脑梗塞组血清hs-CRP、TNF-α及TC、TG、LDL-C等血脂水平均显著升高,而血清HDL-C水平显著降低,其异均具有统计学意义(P＜0.05);与中型脑梗塞组比较,重型脑梗塞组血清TC、TG、LDL-C等血脂水平均显著升高,血清HDL-C水平显著降低,其差异亦均具有统计学意义(P＜0.05).脑梗塞患者血清hs-CRP与TNF-α水平呈显著正相关(P＜0.05),与TC、TG、LDL-C等血脂水平均亦呈显著正相关(P＜0.05),与血清HDL-C水平呈显著负相关(P＜0.05).脑梗塞患者血清hs-CRP、TNF-α水平与病情严重程度呈显著正相关(P＜0.05).结论:检测血清hs-CRP、TNF-α及血脂指标水平对评估脑梗塞患者病情具有重要的临床意义.     

老年急性脑梗塞患者血清TNF-α 和IL-6 水平的变化及其临床意义

目的:观察老年急性脑梗塞(ACI)患者血清TNF-α和IL-6水平的变化并探讨其临床意义.方法:选择老年ACI患者53例,观察以上入选患者入院后第7d、第9d和第11d血清TNF-α和IL-6水平的变化,并与26例健康人对照;同时分析53例老年ACI患者血清TNF-α和IL-6水平与患者脑梗塞面积及神经功能缺损评分的Spearman等级相关性.结果:老年ACI患者血清TNF-α和IL-6水平显著高于健康人(P＜0.01);随着治疗的进展与病情的稳定及恢复,患者血清TNF-α和IL-6水平随之显著下降(P＜0.05);同时患者血清TNF-α和IL-6水平与病变的严重程度呈正相关性(P＜0.05);治疗11d后血清TNF-α和IL-6降低量与病变的严重程度呈正相关性(P＜0.05).结论:在老年ACI患者治疗过程中,应进行血清TNF-α和IL-6水平的动态监测,可提示病变的发生发展并指导临床治疗.     

Ethanolamine Kinase Activity in Purified Myelin of Rat Brain

Highly purified rat brain myelin showed a significant level of ethanolamine kinase, amounting to 17% of the specific activity of whole brain homogenate. This kinase level in myelin was an order of magnitude higher than that of lactate dehydrogenase, a marker for cytosol. Subcellular distribution studies revealed that in addition to myelin, this kinase was present in the P1, P2, P3, and cytosolic fractions with highest relative specific activity in the latter. The possibility that myelin activity resulted from adsorption of the soluble enzyme was unlikely since activity was retained in myelin that had been washed with buffered sodium chloride or taurocholate. Mixing experiments and repeated purification further indicated that the enzyme is intrinsic to myelin. Kinetic studies indicated similar Km values for ethanolamine in the microsomal, cytosolic, and myelin fractions but a significantly lower apparent Km for ATP in myelin. This and other differences suggested the possible existence of isozymes. Establishment of the presence of this kinase completes the list of phospholipid synthesizing enzymes needed to synthesize phosphatidylethanolamine from diacylglycerol within the myelin membrane.     

Proline Reduces Creatine Kinase Activity in the Brain Cortex of Rats

Type II hyperprolinemia is an inherited disorder caused by a deficiency of ¹-pyrroline-5-carboxilic acid dehydrogenase, whose biochemical hallmark is proline accumulation in plasma and tissues. Although neurological symptoms occur in most patients, the neurotoxicity of proline is still controversial. The main objective of the present study was to investigate the effect of acute and chronic administration of proline on creatine kinase activity of brain cortex of Wistar rats. Acute treatment was performed by subcutaneous administration of one injection of proline to 22-day-old rats. For chronic treatment, proline was administered twice a day from the 6th to the 21st postpartum day. The results showed that creatine kinase activity was significantly inhibited in the brain cortex of rats subjected to acute proline administration. In contrast, this activity was increased in animals subjected to chronic administration. We also measured the in vitro effect of proline on creatine kinase activity in cerebral cortex of 22-day-old nontreated rats. Proline significantly inhibited creatine kinase activity. Considering the importance of creatine kinase forthe maintenance of energy homeostasis in the brain, it is conceivable that an alteration of this enzyme activity in the brain may be one of the mechanisms by which proline might be neurotoxic.     

脑缺血Akt和MAPK磷酸酶负性调节c-Jun N端激酶信号通路

目的：探讨脑缺血再灌后Akt和MAPK磷酸酶与JNK活性下调的关系。方法：采用成年清洁级雄性SD大鼠,建立四动脉阻断前脑缺血再灌注模型。缺血10min后再灌注不同时间（15min,1h,4h,24h）。侧脑室分别给予P13K抑制剂LY294002（LY）和MAPK磷酸酶抑制剂放线菌酮（CHO）。免疫印迹观察P-Akt和P-JNK蛋白水平变化。结果：脑缺血再灌注4h,JNK的活性能被Akt抑制剂LY294002增强,表明激活的Akt能够下调JNK信号通路。而MAPK磷酸酶抑制剂放线茵酮能上调缺血后JNK活性,提示MAPK磷酸酶通过去磷酸化参与了JNK的活性抑制。结论：前脑缺血再灌后,激活Akt和MAPK磷酸酶参与了JNK信号通路负性调节,是抑制JNK诱导缺血后中枢神经损伤的重要机制。     

川陈皮素对脑梗死缺血再灌注大鼠的保护作用及其机制研究

摘要 目的：研究川陈皮素对脑梗死缺血再灌注大鼠的保护作用及其机制。方法：将90只雄性Wistar大鼠随机分为空白对照组、假手术组、模型组及低剂量组、中剂量组及高剂量组,每组15只。空白对照组不予以任何处理,模型组、低剂量组、中剂量组及高剂量组其余各组大鼠均采用Long线栓法构建脑梗死缺血再灌注模型,假手术组除了不插入拴线,其他操作和模型组相同。造模后,空白对照组、假手术组及模型组分别予以10 mL/（kg?d）的生理盐水灌胃,低剂量组、中剂量组、高剂量组分别予以10 mL/（kg?d）、15 mL/（kg?d）、20 mL/（kg?d）川陈皮素灌胃。检测各组大鼠梗死面积以及神经细胞凋亡率,缺氧诱导因子-1α（HIF-1α）、血管内皮生长因子（VEGF）水平,炎症细胞因子水平,B淋巴细胞瘤-2（Bcl-2）,Bcl-2相关X蛋白（Bax）,半胱氨酸天冬氨酸蛋白酶-3（caspase-3）表达情况。结果：模型组、低剂量组、中剂量组、高剂量组梗死面积、神经细胞凋亡率以及HIF-1α、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-β）、Bax mRNA、caspase-3 mRNA水平均高于空白对照组及假手术组;且低剂量组、中剂量组、高剂量组较模型组低;降低呈剂量依赖性（均P＜0.05）。模型组、低剂量组、中剂量组、高剂量组VEGF、Bcl-2 mRNA水平均低于空白对照组及假手术组;且低剂量组、中剂量组、高剂量组较模型组高;降低呈剂量依赖性（均P＜0.05）。假手术组梗死面积以及神经细胞凋亡率均高于空白对照组（均P＜0.05）。结论：川陈皮素对脑梗死缺血再灌注大鼠的保护作用明显,其主要机制可能与调控HIF-1α、VEGF、炎症细胞因子以及凋亡相关基因表达有关。     

脑缺血Akt 和MAPK 磷酸酶负性调节c-Jun N 端激酶信号通路

目的:探讨脑缺血再灌后Akt和MAPK磷酸酶与JNK活性下调的关系。方法:采用成年清洁级雄性SD大鼠,建立四动脉阻断前脑缺血再灌注模型。缺血10min后再灌注不同时间(15min,1h,4h,24h)。侧脑室分别给予PI3K抑制剂LY294002(LY)和MAPK磷酸酶抑制剂放线菌酮(CHO)。免疫印迹观察p-Akt和p-JNK蛋白水平变化。结果:脑缺血再灌注4h,JNK的活性能被Akt抑制剂LY294002增强,表明激活的Akt能够下调JNK信号通路。而MAPK磷酸酶抑制剂放线菌酮能上调缺血后JNK活性,提示MAPK磷酸酶通过去磷酸化参与了JNK的活性抑制。结论:前脑缺血再灌后,激活Akt和MAPK磷酸酶参与了JNK信号通路负性调节,是抑制JNK诱导缺血后中枢神经损伤的重要机制。     

Regional Alterations of Protein Kinase C Activity Following Transient Cerebral Ischemia: Effects of Intraischemic Brain Temperature Modulation

Abstract: It is well established that ischemia-induced release of glutamate and the subsequent activation of postsynaptic glutamate receptors are important processes involved in the development of ischemic neuronal damage. Moderate intraischemic hypothermia attenuates glutamate release and confers protection from ischemic damage, whereas mild intraischemic hyperthermia increases glutamate release and augments ischemic pathology. As protein kinase C (PKC) is implicated in neurotransmitter release and glutamate receptor-mediated events, we evaluated the relationship between intraischemic brain temperature and PKC activity in brain regions known to be vulnerable or nonvulnerable to transient global ischemia. Twenty minutes of bilateral carotid artery occlusion plus hypotension were induced in rats in which intraischemic brain temperature was maintained at 30°C, 37°C, or 39°C. Prior to and following ischemia, brain temperature was 37°C in all groups. Cytosolic, membrane-bound, and total PKC activities were determined in hippocampal, striatal, cortical, and thalamic homogenates at the end of ischemia and at 0.25–24 h of recirculation. PKC activity of control rats varied by region and were affected by altered brain temperature. For both membrane-bound and cytosolic PKC, there was a significant temperature effect, and for membrane-bound PKC there was also a significant effect of region. Rats with normothermic ischemia (37°C) showed extensive depressions of all PKC fractions. Hippocampus and striatum were noteworthy for depressions in PKC activity extending from the earliest (15 min) to the latest (24 h) recirculation times studied, whereas cortex showed PKC depressions chiefly during the first hour of recirculation, and the thalamic pattern was inconsistent. In contrast, in rats with hypothermic ischemia (30°C), significant overall effects were noted only for total PKC in thalamus, which showed depressed levels at both 1 and 24 h of recirculation. Rats with hyperthermic (39°C) ischemia also showed significant overall effects for the time course of membrane-bound, cytosolic, and total PKC activities in the hippocampus, striatum, and cortex. However, no significant reductions in PKC indices were observed in the thalamus. For membrane-bound PKC, significant temperature effects were noted for hippocampus, striatum, and cortex, but not for thalamus. For cytosolic, as well as total PKC, activity, significant temperature effects were noted for all four brain regions. Our results indicate that ischemia, followed by reperfusion, induces a significant reduction in PKC activity and that this process is highly influenced by the brain temperature during ischemia. Furthermore, our data also establish that differences exist in the response of PKC to ischemia/recirculation in vulnerable versus non-vulnerable brain regions. These results suggest that PKC alterations may be an important factor involved in the modulatory effects of temperature on the outcome following transient global ischemia.     

Cdk5与大鼠脑缺血再灌注损伤时细胞凋亡的关系

目的利用大鼠可逆性大脑中动脉栓塞模型（MCAO）,研究周期素依赖性蛋白激酶5（cyclin dependent kinase5,Cdk5）对视网膜母细胞瘤蛋白（Rb）的磷酸化作用与细胞凋亡的关系。方法线栓法制作大鼠MCAO模型,随机分为再灌注0、3、6、9、24h组。通过免疫组化染色观察缺血侧大脑Cdk5和磷酸化Rb的数量和变化,TUNEL标记法检测凋亡神经元数量和变化,Western blot检测不同再灌注时间Cdk5蛋白水平的表达。结果缺血侧cdk5随再灌注时间增加而增加,24h达到高峰;再灌注6h出现磷酸化的视网膜母细胞瘤蛋白（pRb）,并随再灌注时间增加而增加,24h达到高峰。缺血侧凋亡阳性细胞变化趋势与Cdk5基本一致。缺血侧Cdk5蛋白的表达随再灌注时间增加而增加,缺血对侧无明显变化。结论大鼠局限性脑缺血再灌注损伤可以诱导Cdk5数量和激酶活性增加,通过底物磷酸化作用引起神经细胞凋亡。     

Decreased Protein Kinase C Activity During Cerebral Ischemia and After Reperfusion in the Adult Rat

The possible activation of protein kinase C (PKC) during total cerebral ischemia was investigated in the rat. Translocation of PKC activity from the soluble to the particulate fraction was used as an index of PKC activation. There was a drop in the proportion of particulate PKC activity from 30% for controls to 20% by 30 min of ischemia (p less than 0.01). By 20 min of cardiac arrest, there was a 40% decline of the total cellular PKC activity (p less than 0.01). This was not accompanied by an increase in activator-independent activity, a finding indicating PKC was not being converted to protein kinase M. These data suggest that PKC was not activated during ischemia, but rather that ischemia causes a reduction in cellular PKC activity. Translocation of PKC activity to the particulate fraction was not observed in the cerebral cortex or hippocampus of reperfused brain for up to 6 h of recovery following 11-13 min of total cerebral ischemia. The level of total, soluble, and particulate PKC activity in the cerebral cortex was reduced (p less than 0.05), corresponding to the decrease observed by 15 min of ischemia without reflow. A similar decline in activity was also observed in the hippocampus. No increase in activator-independent activity was observed. These data suggest that PKC was inhibited during cerebral ischemia and that this reduced level of PKC activity was maintained throughout 6 h of recovery. We conclude that pathological activation of PKC was not responsible for the evolution of ischemic brain damage.     

去纤酶治疗较长时间脑梗死

目的　观察去纤酶治疗较长时间脑梗死的疗效。　方法　 3 0 0例发病时间 >6h的急性脑梗死患者 ,给予静滴去纤酶 1 0 u,每天 1次 ,连用 3天为 1个疗程。全部病例均用 1～ 2个疗程 ,并与灯盏花素和复方丹参治疗的 2 95例患者进行疗效比较。　结果　治疗组基本治愈、显著进步及患肢功能恢复明显优于对照组 ( P <0 .0 1 )。　结论　脑梗死后超过 6h,经溶栓治疗仍有较好疗效。     

高强度间歇运动对脑梗死后大鼠的脑保护作用及HDAC6表达的影响

为了考察高强度间歇运动(HIIE)对脑梗死后大鼠的脑保护作用及组蛋白去乙酰化酶6 (HDAC6)表达的影响。本研究将60只SD大鼠随机分为3组,假手术组、大脑中动脉闭塞模型组和HIIE组,每组20只。HIIE组大鼠在建模48 h后进行4周的高强度间歇运动,其他组大鼠不进行运动。通过神经损伤评分来评价大鼠神经功能,TTC染色检测梗死面积,TUNEL染色测定脑组织的细胞凋亡,RT-PCR和Western blotting检测大鼠海马组织中HDAC6、TNF-α、IL-1β和IL-6的m RNA和蛋白表达。研究发现,高强度间歇运动后,HIIE组的神经损伤评分显著低于模型组(p<0.05)。TTC染色显示,HIIE组的梗死面积比例显著低于模型组(p<0.05)。TUNEL染色显示,HIIE组的海马神经细胞凋亡数显著低于模型组(p<0.05)。RT-PCR和Western blotting结果显示,HIIE组的HDAC6、TNF-α、IL-1β和IL-6 m RNA和蛋白表达水平均显著低于模型组(p<0.05)。本研究表明,高强度间歇运动可显著改善脑梗死大鼠的神经功能,降低脑梗死面积,抑制海马神经细胞凋亡。高强度间歇运动的神经保护作用机制可能与抑制HDAC6有关。