阻断缝隙连接对脑缺血后海马迟发性神经元凋亡的影响

目的探讨阻断缝隙连接(gap junction)通讯对大鼠局灶性脑缺血后海马迟发性神经元死亡(delayed neuronal death,DND)及Bcl-2蛋白表达的影响。方法术前2h左侧脑室注射缝隙连接阻断剂甘珀酸(carbenoxolone,CBX),对照组左侧脑室注射生理盐水,颈内动脉插线法制备大鼠大脑中动脉缺血再灌注模型,采用DNA原位末端标记TUNEL技术及免疫荧光技术,观察阻断缝隙连接对大鼠局灶性脑缺血3d后海马迟发性神经元死亡及BCL-2蛋白表达的影响。结果不给予缝隙连接阻断剂,大脑中动脉缺血模型有45%的大鼠在术后3d出现海马迟发性神经元死亡;用甘珀酸阻断缝隙连接后,30%的大鼠出现海马迟发性神经元死亡,其发生率明显减小(P<0.01);与对照组相比,干预组Bcl-2蛋白的表达较高(P<0.01),两组Bcl-2蛋白的表达均高于假手术组(P<0.01)。结论阻断缝隙连接通讯可以减少局灶性脑缺血后海马迟发性神经元死亡的发生率,Bcl-2参与了局灶性脑缺血后海马神经元凋亡的调节。     

大鼠局灶性脑缺血后磷酸化的细胞周期相关蛋白的表达

目的探讨细胞周期对于大鼠局灶性脑缺血后神经元的影响。方法采用MCAO方法制作大鼠局灶性脑缺血模型,应用免疫荧光技术观察缺血后1d、3d、7d、14d大鼠缺血侧病灶周围神经元中磷酸化细胞周期蛋白CDK2、CDC2及磷酸化Rb的表达。结果与正常对照组相比,缺血后1d、3d组磷酸化CDK2和磷酸化Rb的表达量明显增加（P〈0．05）。缺血后7d、14d组磷酸化CDK2和磷酸化Rb的表达量无增加。磷酸化CDC2在正常组及缺血组均无明显表达。结论大鼠局灶性脑缺血后早期部分神经元再次进入细胞周期,提示细胞周期调控参与了大鼠局灶性脑缺血后神经元的凋亡。     

ATP敏感性钾通道开放剂对脑缺血再灌注损伤的保护作用

目的探讨ATP敏感性钾通道开放剂对大鼠局灶性脑缺血再灌注损伤的保护作用。方法40只Wistar雄性大鼠随机分为四组:A组(假手术组)、B组(缺血组)、C组(KATP开放剂治疗组)及D组(KATP开放剂 阻断剂治疗组)。应用线栓法制备大鼠大脑中动脉缺血模型(MCAO),应用TUNEL法检测神经元凋亡,应用免疫组化方法检测Caspase-3蛋白表达,并观察脑梗死体积及神经功能缺损评分。结果(1)C组脑梗死体积显著小于B、D组(P<0.01),B、D组之间无显著性差异(P>0.05);(2)C组神经功能缺损程度较B、D组显著减轻(P<0.05),B、D组之间无显著性差异(P>0.05);(3)C组神经元凋亡数较B、D组显著减少(P<0.01),B、D组之间无显著性差异(P>0.05);(4)C组Caspase-3蛋白表达显著少于B、D组(P<0.01),B、D组之间无显著性差异(P>0.05)。结论KATP通道开放剂能显著减轻脑缺血再灌注后脑梗死体积、改善神经功能缺损程度、减少Caspase-3蛋白表达、抑制神经元凋亡,对脑缺血再灌注损伤发挥保护作用。     

大鼠局灶性脑缺血后不同时间点磷酸化Rb蛋白与凋亡神经元的共定位研究

目的探讨大鼠局灶性脑缺血后磷酸化Rb蛋白(p-Rb,ser 795)的表达定位与神经元凋亡的时空关系。方法制备大鼠大脑中动脉梗塞(MCAO)模型,分为假手术对照组、缺血1h再灌注12h,1d,3d,7d组。利用TUNEL法检测缺血周边区细胞凋亡情况;TUNEL与p-Rb荧光双标观察神经元凋亡与p-Rb表达、定位的关系。结果缺血半暗带内大部分TUNEL阳性细胞为神经元;大鼠MCAO再灌注12h和1d,TUNEL与p-Rb分别以重叠和镶嵌的方式共定位;再灌注3d,7d发生p-Rb核浆转移的神经元与TUNEL染色细胞仍然分别维持在高水平,但是两者却没有明显的共定位关系。结论 p-Rb可能参与短暂局灶脑缺血后神经元早期凋亡过程,间接或者不参与神经元晚期凋亡过程。     

细胞周期调控对大鼠全脑缺血后海马迟发性神经元死亡的影响

目的观察细胞周期调控对大鼠全脑缺血再灌流后海马区迟发性神经元死亡(delayed neuronal death,DND)以及星形胶质细胞的活化、增殖的影响.方法建立大鼠短暂性全脑缺血再灌流模型,利用尼氏染色、TUNEL、免疫组织化学方法观察再灌流后细胞周期素依赖的蛋白激酶(cyclin depedent kinase, CDK)抑制剂Olomoucine对海马DND以及星形胶质细胞活化增殖的影响.结果全脑缺血再灌流后3d、7d、30d海马神经元明显脱失,部分CA1、CA2区神经元凋亡;星形胶质细胞数目增多,GFAP表达上调,应用Olomoucine后TUNEL阳性神经元数目明显减少,幸存神经元数目增加;星形胶质细胞数目无明显增多,GFAP表达明显下调.结论 CDK抑制剂Olomoucine可有效抑制大鼠全脑缺血后海马神经元DND以及星形胶质细胞活化增殖.     

甘珀酸干预对大鼠脑缺血再灌注损伤的影响

目的观察缝隙连接阻断剂甘珀酸对局灶性脑缺血/再灌注损伤的影响。方法采用大鼠大脑中动脉阻塞再灌流模型（MCAO）,将动物随机分为脑缺血60min再灌注（MCAO）组,脑缺血再灌注加甘珀酸干预（MCAO＋CBX）组和假手术组（sham）。采用尼氏染色显示脑梗死灶并计算梗死灶体积;应用免疫荧光与TUNEL染色法分别观察脑缺血后3d与7d不同时间点缺血边缘区胶质纤维酸性蛋白（GFAP）的表达和细胞凋亡情况。结果（1）缺血后3d、7d MCAO＋CBX组大鼠梗死体积小于MCAO组,3d、7d MCAO＋CBX组大鼠梗死体积较MCAO组分别缩小5%和4.6%;（2）缺血后3d、7d于缺血边缘区可见大量TUNEL阳性染色细胞,且MCAO组大鼠缺血边缘区细胞凋亡数目明显多于MCAO＋CBX大鼠（P〈0.001）;（3）缺血后3d和7d组缺血边缘区GFAP表达明显增强,3d的MCAO组与MCAO＋CBX组大鼠缺血边缘区GFAP的表达均较假手术组强（P〈0.05）,7d的MCAO＋CBX组大鼠缺血边缘区GFAP的表达较假手术组强（P〈0.001）,但明显弱于MCAO组大鼠（P〈0.01）;结论缝隙连接阻断剂甘珀酸可减少大鼠大脑中动脉阻塞后脑梗死体积,其机制可能与阻断缝隙连接后缺血边缘区神经元凋亡降低有关,星型胶质细胞的反应性变化参与了该过程。     

促红细胞生成素对大鼠局灶性脑缺血再灌注神经元的保护作用及P53蛋白的表达

目的:探讨促红细胞生成素(Epo)对大鼠局灶性脑缺血再灌注神经细胞的保护作用.方法:60只SD大鼠随机分为缺血再灌注Epo治疗组(又分为高剂量A组、低剂量B组)、缺血再灌注组(C组)及假手术组(D组),采用大脑中动脉线栓法制备大鼠局灶性脑缺血再灌注模型.参考Longa的5分制法在大鼠麻醉清醒后进行评分,TTC染色法观察线栓侧的梗死体积,并检测脑组织含水量的变化,HE染色法观察脑缺血再灌注后脑组织的病理变化,TUNEL法观察神经细胞凋亡情况,western blot法观察p53蛋白的表达变化.结果:对照组比较,大鼠脑缺血再灌注后出现不同程度的脑梗死,24h后缺血中心区及周围区均可见到p53蛋白表达.缺血再灌注6h内给予Epo可显著改善大鼠神经功能评分,减少梗死体积及脑组织含水量,减轻病理学变化及神经细胞凋亡.结论:Epo通过调控神经细胞凋亡、改善缺血再灌注损伤而发挥脑保护作用,P53蛋白参与缺血再灌注后神经细胞凋亡机制.     

早期跑步运动对大鼠脑缺血/再灌注损伤后神经行为与神经元凋亡的影响

目的: 探讨早期跑步运动对大鼠脑缺血后神经行为与神经元凋亡的影响。方法:雄性SD大鼠随机分为4组:假手术+安静组(Sham-St、假手术+运动组(Sham-Ex)、缺血(大脑中动脉闭塞(MCAO) +运动组((MCAO -Ex)和缺血+安静组(MCAO-St),每组15只。MCAO-Ex 和 MCAO-St 组大鼠行MCAO 60 min,再灌注2 d后,MCAO-Ex 和Sham-Ex大鼠在跑步机上进行5 d的30 min/d跑步运动(15 m/min),之后进行神经行为学评价,最后大鼠断头取脑进行TTC方法染色,评估各组大鼠梗死体积以及缺血半影Caspase-3和TUNEL阳性细胞表达水平。结果:与Sham-St相比,MCAO-St和MCAO-Ex大鼠缺血半影区Caspase-3表达均显著升高 (P＜0.05);与MCAO-St 组大鼠相比,MCAO-Ex组大鼠脑梗死体积明显减少,大鼠神经功能评分明显改善,大鼠缺血半影区Caspase-3和TUNEL阳性细胞表达水平显著降低 (P＜0.05)。结论: 早期运动可能通过抑制大鼠脑缺血后神经元凋亡发挥神经保护作用。     

大鼠局灶性脑缺血再灌注损伤中iNOS在大脑皮层和海马的表达

目的研究局灶性脑缺血再灌注损伤中iNOS在不同脑区的表达.方法用改良的血管内栓线技术制造大鼠局灶性脑缺血与再灌注模型,应用免疫组织化学技术检测脑组织中的iNOS的表达.结果 (1)脑缺血再灌注损伤24h后,缺血组缺血侧大脑皮层、海马CA1区、CA3区神经元iNOS的表达显著增强,与正常对照组比较有显著性差异(P<0.05);(2)脑缺血再灌注损伤24h后,缺血组对照侧大脑皮层、海马CA1区、CA3区神经元iNOS的表达也明显增强,与正常对照组比较有显著性差异(P<0.05);(3) 与对照侧比较,脑缺血再灌注大鼠缺血侧皮质的iNOS表达显著增强(P<0.05),而海马CA1区、CA3区缺血侧的iNOS表达与对照侧相比无显著性差异(P>0.05).结论局灶性脑缺血再灌注损伤后,缺血侧皮层和海马iNOS表达显著升高,未缺血脑区(对照侧)iNOS反应性也较对照组者升高.     

脑缺血后大鼠神经元和星形胶质细胞P21cip1表达的研究

目的研究大鼠局灶性脑缺血再灌注损伤后细胞周期蛋白依赖性激酶抑制因子P21cip1在神经元和星形胶质细胞的表达。方法建立大鼠大脑中动脉阻塞(MCAo)再灌注模型,应用流式细胞术检测各组MCAo再灌注后不同时期神经元和星形胶质细胞中的P21cip1的表达。结果缺血侧皮层区星形胶质细胞和神经元中的P21cip1的表达在再灌注3d、7d、14d后表达下调,与假手术组比较有显著性差异(P<0.05);神经元中的P21cip1的表达和星形胶质细胞中的P21cip1的表达无显著性差异(P>0.05)。结论局灶性脑缺血再灌注损伤后,缺血侧皮层区星形胶质细胞和神经元的p21cip1表达下调。     

UCF-101对大鼠局灶性脑缺血再灌注后JNK和ERK活性的影响

目的:探讨UCF-101对局灶性脑缺血再灌注大鼠脑内c-Jun氨基末端激酶(JNK)和胞外信号调节酶(ERK)活性的影响,进一步探讨UCF-101对局灶性脑缺血再灌注损伤脑保护作用的机制。方法:采用大脑中动脉线栓法(MCAO)建立大鼠局灶性脑缺血再灌注模型,随机分为假手术组,缺血再灌注组,UCF组,应用TTC检测大鼠脑梗死体积,TUNEL法检测神经元凋亡,Western blot检测ERK和JNK的活性。结果:UCF-101可下调脑缺血再灌注大鼠脑组织JNK蛋白的活性,上调ERK蛋白的活性,并降低梗死体积、坏死和凋亡细胞数。结论:UCF-101对大鼠局灶性脑缺血再灌注损伤有保护作用,抑制JNK凋亡通路、促进ERK生存通路,从而减轻细胞凋亡是其脑保护机制之一。     

Vagus Nerve Stimulation Attenuates Cerebral Ischemia and Reperfusion Injury via Endogenous Cholinergic Pathway in Rat

Inflammation and apoptosis play critical roles in the acute progression of ischemic injury pathology. Emerging evidence indicates that vagus nerve stimulation (VNS) following focal cerebral ischemia and reperfusion (I/R) may be neuroprotective by limiting infarct size. However, the underlying molecular mechanisms remain unclear. In this study, we investigated whether the protective effects of VNS in acute cerebral I/R injury were associated with anti-inflammatory and anti-apoptotic processes. Male Sprague-Dawley (SD) rats underwent VNS at 30 min after focal cerebral I/R surgery. Twenty-four h after reperfusion, neurological deficit scores, infarct volume, and neuronal apoptosis were evaluated. In addition, the levels of pro-inflammatory cytokines were detected using enzyme-linked immune sorbent assay (ELISA), and immunofluorescence staining for the endogenous “cholinergic anti-inflammatory pathway” was also performed. The protein expression of a7 nicotinic acetylcholine receptor (a7nAchR), phosphorylated Akt (p-Akt), and cleaved caspase 3 in ischemic penumbra were determined with Western blot analysis. I/R rats treated with VNS (I/R+VNS) had significantly better neurological deficit scores, reduced cerebral infarct volume, and decreased number of TdT mediated dUTP nick end labeling (TUNEL) positive cells. Furthermore, in the ischemic penumbra of the I/R+VNS group, the levels of pro-inflammatory cytokines and cleaved caspase 3 protein were significantly decreased, and the levels of a7nAchR and phosphorylated Akt were significantly increased relative to the I/R alone group. These results indicate that VNS is neuroprotective in acute cerebral I/R injury by suppressing inflammation and apoptosis via activation of cholinergic and a7nAchR/Akt pathways.     

Gadd45b is a Novel Mediator of Neuronal Apoptosis in Ischemic Stroke

Apoptosis plays an essential role in ischemic stroke pathogenesis. Research on the process of neuronal apoptosis in models of ischemic brain injury seems promising. The role of growth arrest and DNA-damage-inducible protein 45 beta (Gadd45b) in brain ischemia has not been fully examined to date. This study aims to investigate the function of Gadd45b in ischemia-induced apoptosis. Adult male Sprague-Dawley rats were subjected to brain ischemia by middle cerebral artery occlusion (MCAO). RNA interference (RNAi) system, which is mediated by a lentiviral vector (LV), was stereotaxically injected into the ipsilateral lateral ventricle to knockdown Gadd45b expression. Neurologic scores and infarct volumes were assessed 24 h after reperfusion. Apoptosis-related molecules were studied using immunohistochemistry and Western blot analysis. We found that Gadd45b-RNAi significantly increased infarct volumes and worsened the outcome of transient focal cerebral ischemia. Gadd45b-RNAi also significantly increased neuronal apoptosis as indicated by increased levels of Bax and active caspase-3, and decreased levels of Bcl-2. These results indicate that Gadd45b is a beneficial mediator of neuronal apoptosis.     

Bid-mediated mitochondrial pathway is critical to ischemic neuronal apoptosis and focal cerebral ischemia

We have investigated the role of the BH3-only pro-death Bcl-2 family protein, Bid, in ischemic neuronal death in a murine focal cerebral ischemia model. Wild-type and bid-deficient mice of inbred C57BL/6 background were subjected to 90-min ischemia induced by left middle cerebral artery occlusion followed by 72-h reperfusion. The volume of ischemic infarct was significantly smaller in the bid-deficient brains than in the wild-type brains, suggesting that Bid participated in the ischemic neuronal death. Indeed, following the ischemic treatment there was a significant reduction of apoptosis in the ischemic areas, particularly in the inner infarct border zone (the penumbra), of the bid-deficient brains. In addition, activation of Bid in the wild-type brains could be readily detected at approximately 3 h after ischemia, as evidenced by its proteolytic cleavage and translocation to the mitochondria as determined using Western blot analysis and immunofluorescence staining. Correspondingly, mitochondrial release of cytochrome c could be detected around the same time Bid was cleaved in the wild-type brains. However, no significant cytochrome c release was detected in the bid-deficient brains until 24 h later. This suggests that, although the mitochondrial apoptosis pathway might be activated by multiple mechanisms during focal cerebral ischemia, Bid is critical to its early activation. This notion was further supported by the finding that caspase-3 activation was severely impaired in the bid-deficient brains, whereas activation of caspase-8 was much less affected. Taken together, these data suggest that Bid is activated early in neuronal ischemia in a caspase-8-dependent fashion and that Bid is perhaps one of the earliest and most potent activators of the mitochondrial apoptosis pathway. Thus, the role of Bid in the induction of ischemic neuronal death may render this molecule an attractive target for future therapeutic intervention.     

Vitexin protects brain against ischemia/reperfusion injury via modulating mitogen-activated protein kinase and apoptosis signaling in mice

Vitexin is a major bioactive flavonoid compound derived from the dried leaf of hawthorn (Crataegus pinnatifida), a widely used conventional folk medicine in China. Recent studies have shown that vitexin presents neuroprotective effects in vitro. Whether this protective effect applies to the cerebral ischemia/reperfusion (I/R) injury remains elusive. In the present study, we examined the potential neuroprotective effect of vitexin against cerebral I/R injury and underlying mechanisms. A focal cerebral I/R model in male Kunming mice was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 22 h. The neurological function and infarct volume were assessed by using Long's five-point scale system and triphenyl-tetrazolium chloride (TTC) staining technique, respectively. Neuronal damage was evaluated by histological staining. Extracellular signal-regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinases (JNK) and p38 phosphorylation, and apoptosis were measured via Western blot at 24 h after reperfusion. As a result, systemic vitexin treatment significantly reduced neurological deficit, cerebral infarct volume and neuronal damage when compared with the I/R group. Western blot analyses revealed that vitexin markedly upregulated p-ERK1/2 and downregulated p-JNK and p-p38. Meanwhile, vitexin increased Bcl-2 expression and suppressed the overexpression of Bax in the I/R injury mice. In conclusion, the results indicate that vitexin protects brain against cerebral I/R injury, and this effect may be regulated by mitogen-activated protein kinase (MAPK) and apoptosis signaling pathways.     

Propofol Reduces Inflammatory Reaction and Ischemic Brain Damage in Cerebral Ischemia in Rats

Our previous studies demonstrated that inflammatory reaction and neuronal apoptosis are the most important pathological mechanisms in ischemia-induced brain damage. Propofol has been shown to attenuate ischemic brain damage via inhibiting neuronal apoptosis. The present study was performed to evaluate the effect of propofol on brain damage and inflammatory reaction in rats of focal cerebral ischemia. Sprague–Dawley rats underwent permanent middle cerebral artery occlusion, then received treatment with propofol (10 or 50 mg/kg) or vehicle after 2 h of ischemia. Neurological deficit scores, cerebral infarct size and morphological characteristic were measured 24 h after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was assessed 24 h after cerebral ischemia. Nuclear factor-kappa B (NF-κB) p65 expression in ischemic rat brain was detected by western blot. Cyclooxygenase-2 (COX-2) expression in ischemic rat brain was determined by immunohistochemistry. ELISA was performed to detect the serum concentration of tumor necrosis factor-α (TNF-α). Neurological deficit scores, cerebral infarct size and MPO activity were significantly reduced by propofol administration. Furthermore, expression of NF-κB, COX-2 and TNF-α were attenuated by propofol administration. Our results demonstrated that propofol (10 and 50 mg/kg) reduces inflammatory reaction and brain damage in focal cerebral ischemia in rats. Propofol exerts neuroprotection against ischemic brain damage, which might be associated with the attenuation of inflammatory reaction and the inhibition of inflammatory genes.     

Neuroprotective Effect of Baicalin in a Rat Model of Permanent Focal Cerebral Ischemia

This investigation was performed to determine the neuroprotective effect of baicalin on permanent cerebral ischemia injury in rats and the potential mechanisms in this process. Adult male Sprague-Dawley rats underwent permanent middle cerebral artery occlusion (pMCAO). The rats were then received intraperitoneal injection with baicalin (10, 30 and 100 mg/kg) or vehicle. Morphological characteristic, neurological deficit scores, cerebral infarct volume and the enzymatic activity of myeloperoxidase (MPO) were measured 24 h after pMCAO. The mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were determined by RT-PCR. Neuronal apoptosis was determined by TUNEL staining and Western blot. Baicalin (30 and 100 mg/kg) reduced neurological deficit scores and cerebral infarct volume 24 h after pMCAO. Baicalin significantly decreased the enzymatic activity of MPO and the expression of iNOS mRNA and COX-2 mRNA in rat brain, it also significantly inhibited neuronal apoptosis and the expression of cleaved caspase-3 protein after pMCAO. Our results suggested that baicalin possesses potent anti-inflammatory and anti-apoptotic properties and attenuates cerebral ischemia injury. This protection might be associated with the downregulated expression of iNOS mRNA, COX-2 mRNA, and cleaved caspase-3 protein.     

Neuroprotection of Cytisine Against Cerebral Ischemia–Reperfusion Injury in Mice by Regulating NR2B-ERK/CREB Signal Pathway

The aim of the study was to elucidate the therapeutic effects of Cytisine (CYT) on cerebral ischemia–reperfusion injury in mice. Male ICR mice were pretreated with reagents (drug), and then subjected to 2 h focal cerebral ischemia and 24 h reperfusion. Morphologically, the histopathological impairment were estimated by the TTC, HE and TUNEL staining. The expression of GluN2B-containing NMDA receptor, phosphorylation of extracellular regulated protein kinases, total ERK, phosphorylation of cAMP-response element binding protein and total CREB were determined by immunofluorescence and Western blot assay, respectively. The mRNA expression of NR2B, ERK and CREB were quantified by the real-time RT-PCR. CYT significantly diminished the infarct size and neuronal apoptosis. Additionally, it ameliorated histopathological lesion dramatically. CYT promoted the phosphorylation of ERK, CREB and their mRNA expression. In contrast, the expression of NR2B was suppressed in concomitant with the down-regulation of genes. The overall results thus far suggest that CYT confers the neuroprotection against cerebral I/R injury by regulating the NR2B-ERK/CREB signal pathway.     

The Akt/GSK-3β pathway mediates flurbiprofen-induced neuroprotection against focal cerebral ischemia/reperfusion injury in rats

Apoptosis is one of the major mechanisms of cell death during cerebral ischemia and reperfusion injury. Flurbiprofen has been shown to reduce cerebral ischemia/reperfusion injury in both focal and global cerebral ischemia models, but the mechanism remains unclear. This study aimed to investigate the potential association between the neuroprotective effect of flurbiprofen and the apoptosis inhibiting signaling pathways, in particularly the Akt/GSK-3β pathway. A focal cerebral ischemia rat model was subjected to middle cerebral artery occlusion (MCAO) for 120 min and then treated with flurbiprofen at the onset of reperfusion. The infarct volume and the neurological deficit scores were evaluated at 24 h after reperfusion. Cell apoptosis, apoptosis-related proteins and the levels of p-Akt and p-GSK-3β in ischemic penumbra were measured using TUNEL and western blot. The results showed that administration of flurbiprofen at the doses of 5 and 10 mg/kg significantly attenuated brain ischemia/reperfusion injury, as shown by a reduction in the infarct volume, neurological deficit scores and cell apoptosis. Moreover, flurbiprofen not only inhibited the expression of Bax protein and p-GSK-3β, but also increased the expression of Bcl-2 protein, the ratio of Bcl-2/Bax as well as the P-Akt level. Taken together, these results suggest that flurbiprofen protects the brain from ischemia/reperfusion injury by reducing apoptosis and this neuroprotective effect may be partly due to the activation of Akt/GSK-3β signaling pathway.     

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。