干扰素调节因子-1与缺血性脑损伤

干扰素调节因子-1（1RF-1）参与炎症、细胞周期和细胞凋亡等的分子机制。研究表明，缺血性脑损伤后期1RF-1的表达明显增加，表明其是在基因水平参与缺血性脑损伤正反馈机制的因子，是联系脑缺血早期和晚期损伤的重要因子之一。因此，1RF-1成为在脑缺血治疗中阻断级联反应的靶点之一。     

β淀粉样蛋白及其前体蛋白与缺血性脑损伤

β淀粉样蛋白 (Aβ)及其前体蛋白 (APP)沉积被认为是Alzheimer病的特征性病理改变之一。近年的研究表明 ,在缺血性脑损伤后 ,APP Aβ也发生沉积 ,因此APP Aβ可能参与了脑缺血后脑损伤的发生与发展。文章综述了APP Aβ在缺血性脑损伤后的表达、作用和机制     

β淀粉样蛋白及其前体蛋白与缺血性脑损伤

β淀粉样蛋白（Ａβ）及其前体蛋白（ＡＰＰ）沉积被认为是Ａｌｚｈｅｉｍｅｒ病的特征性病理改变之一。近年的研究表明,在缺血性脑损伤后,ＡＰＰ／Ａβ也发生沉积,因此ＡＰＰ／Ａβ可能参与了脑缺血后脑损伤的发生与发展。文章综述了ＡＰＰ／Ａβ在缺血性脑损伤后的表达,作用和机制。     

单胺类神经递质与缺血性脑损伤

脑缺血后，脑组织内单胺类神经递质代谢紊乱，在缺血性脑损伤及迟发性神经元死亡（ＤＮＤ）中起重要作用。文章介绍了脑缺血时单胺类神经递质的变化及其机制，以及其对神经元、局部脑血流（ｒＣＢＦ）和脑代谢的影响；并探讨了其与兴奋性氨基酸（ＥＡＡ）、自由基、神经营养因子（ＮＦ）、细胞凋亡在缺血性脑损伤中的相互关系。     

细胞间黏附分子-1与缺血性脑损伤

细胞间黏附分子-1(ICAM-1)是介导白细胞与内皮细胞黏附的主要分子之一。文章重点阐述了ICAM-1在脑缺血时的表达及其在脑缺血中的作用,探讨了脑缺血时ICAM-1与其他炎性细胞因子之间的相互作用。抗黏附分子治疗有望成为治疗缺血性脑损伤的一种有效手段之一。     

局灶性脑缺血损伤后HIF-1α双重调节作用的研究进展

低氧诱导因子-1α(HIF-1α)是一种核转录因子,通过诱导多个目的基因转录表达在缺血性脑损伤调节中发挥重要作用。局灶性脑缺血发生后,HIF-1α表现为保护缺血性脑损伤和促受损神经元细胞死亡的双重作用,两种作用可能与缺血性脑损伤的严重程度、持续时间、病理性刺激类型以及神经细胞种类有关。现综述HIF-1α在局灶性脑缺血损伤后的调节作用。     

单胺类神经递质与缺血性脑损伤

脑缺血后，脑组织内单胺类神经递质代谢紊乱，在缺血性脑损伤及迟发性神经元死亡（ＤＮＤ）中起重要作用。文章介绍了脑缺血时单胺类神经递质的变化及其机制，以及其对神经元、局部脑血流（ｒＣＢＦ）和脑代谢的影响；并探讨了其与兴奋性氨基酸（ＥＡＡ）、自由基、神经营养因子（ＮＦ）、细胞凋亡在缺血性脑损伤中的相互关系。     

中医药调控胶质细胞源性神经营养因子保护脑缺血再灌注损伤的研究进展

<正>缺血性脑血管病(ICVD)是目前威胁人类健康的主要疾病之一,约占全部脑血管病的59.2%~85%〔1〕。缺血性脑损伤包括缺血期原发性损伤和再灌注期继发性损伤。脑缺血再灌注损伤(CIRI)可发生于多种脑血管疾病中,其病理生理过程是多因素、多环节、多途径损伤的酶促级联反应,发病机制复杂〔2〕。胶质细胞源性神经营养因子(GDNF)是一种作用广泛的神经营养因子,在中枢和外周神经系统的发育、生长、成熟及损伤修复     

大鼠急性脑缺血时肺脏病理改变及内皮素-1含量变化

目的　探讨脑缺血早期急性肺损伤的病理改变及血浆和支气管肺泡灌洗液中内皮素 1(ET 1)含量变化。方法　用栓线法阻断大鼠右侧大脑中动脉 ,结扎对侧颈总动脉 2 4h ,观察脑与肺病理改变 ,以及血浆和支气管肺泡灌洗液中ET 1含量。结果　脑缺血组光镜下观察可见右侧脑缺血区皮质神经元缺氧变性 ;肺泡隔增宽及中性粒细胞渗出。电镜下观察脑缺血组肺泡II型上皮细胞线粒体肿胀 ,线粒体嵴断裂、消失 ,板层体数量相对减少 ,结构破坏。脑缺血组血浆ET 1(185 .87± 32 .16pg ml)明显增高 ,支气管肺泡灌洗液中ET 1含量呈增高趋势 (38.11± 10 .0pg ml)。结论　大鼠急性脑缺血早期即可出现明显的肺脏病理改变 ,血浆ET 1含量明显增高     

代谢型谷氨酸受体1α在大鼠脑缺血再灌注损伤中的基因表达变化

目的　观察大鼠大脑中动脉闭塞 (MCAO)后再灌注不同时点代谢型谷氨酸受体 1α(mGluR1α)的蛋白与基因表达的变化 ,以探讨其在脑缺血再灌注损伤中的意义。方法　 4 8只SD大鼠随机分为假手术组及缺血 2h再灌注 1、3、6、12、2 4、4 8及 72h组 ,用免疫组织化学、逆转录 聚合酶链反应 (RT PCR)技术和HE染色检测各组mGluR1α的蛋白表达、mRNA转录水平及坏死神经元的计数。结果　各缺血再灌注组mGluR1α表达均高于假手术组 ,再灌注 1hmGluR1α的mRNA转录即有升高 ,6h达到高峰 ,mGluR1α蛋白表达从 3h开始增加 ,12h达高峰 ,与神经元损伤程度一致。结论　脑缺血再灌注可引起mGluR1α表达上调 ,且与神经元损伤程度平行 ,提示mGluR1α参与介导了局灶性脑缺血再灌注损伤。     

Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice during Plasmodium berghei blood-stage infection

Mice deficient of functional interferon regulatory factor-1 (IRF-1-/-) by targeted gene disruption infected with a lethal murine malaria strain, Plasmodium berghei ANKA survived longer than its wild-type littermates despite the inability to induce appreciable amounts of interferon-gamma (IFN-gamma) and nitric oxide. In addition, infected IRF-1-/- mice displayed less organ injury with reduced necrosis and inflammation. Both wild-type and IRF-1-/- mice treated with exogenous interleukin-12 (IL-12) suffered extensive organ damage with corresponding up regulation of IFN-gamma, suggesting the pathogenic potential of IL-12 and IFN-gamma. IL-10 is a cytokine produced by CD4+ T lymphocytes belonging to the Th2 subset. Expression of IL-10 in the wild-type mice correlated with the severity of the infection, with higher mRNA expression towards the later stage of infection. In contrast to the wild-type mice, IL-10 levels in the IRF-1-/- mice were induced early in the infection and decreased gradually as the infection progressed. Both untreated and IL-12 treated wild-type mice appeared to follow a Th1-like immune response early in the infection and a Th2-like immune response later in the infection. However, the IRF-1-/- mice were able to launch an altered immune response with a Th2-like immune response early in the infection. These findings suggest that IL-10 expression in the IRF-1-/- mice during the early stage of P. berghei ANKA infection could play an important role in suppressing pathogenic effects of a cell mediated immune response and promoting protective immunity against the parasite.     

新型强效自由基清除剂依达拉奉治疗急性缺血性卒中——从实验室到临床

自由基在缺血性脑损伤过程中起着关键作用,通过不饱和脂肪酸过氧化反应加重细胞膜损伤,进而导致神经无死亡和脑水肿.依达拉奉是一种新型强效自由基清除剂,可通过抑制脑缺血区内皮损伤和缓解神经细胞损害发挥神经保护作用,还能减轻溶栓治疗诱导的再灌注后脑水肿和出血事件.l临床经验提示,依达拉奉的治疗时间窗很宽,与溶栓疗法联合应用能降低卒中病死率和促进神经功能缺损的恢复.文章对依达拉奉从实验事到临床阶段的发展历程做了综述.     

Caveolin-1 deficiency increases cerebral ischemic injury

Caveolins (Cav), the principal structural proteins of the caveolar domains, have been implicated in the pathogenesis of ischemic injury. Indeed, changes in caveolin expression and localization have been reported in renal and myocardial ischemia. Genetic ablation of the Cav-1 gene in mice was further shown to increase the extent of ischemic injury in a model of hindlimb ischemia. However, the role of Cav-1 in the pathogenesis of cerebral ischemia remains unknown. Immunoblot and immunofluorescence analyses of rat brains subjected to middle cerebral artery occlusion revealed marked increases in endothelial Cav-1 and Cav-2 protein levels. To directly assess the functional role of caveolins in the pathogenesis of cerebral ischemic injury, we next investigated the effects of cerebral ischemia in caveolin knockout (KO) mice. Interestingly, Cav-1 KO mice showed a marked increase of cerebral volume of infarction, as compared with wild-type and Cav-2 KO mice. Immunofluorescence analyses showed an increased number of proliferating endothelial cells in wild-type ischemic brains, as compared with Cav-1 KO ischemic brains. Immunoblot analyses of wild-type ischemic brains showed an increase in endothelial nitric oxide synthase protein levels. Conversely, the protein levels of endothelial nitric oxide synthase remained unchanged in Cav-1 KO ischemic brains. TUNEL analysis also showed increased apoptotic cell death in Cav-1 KO ischemic brains, as compared with wild-type ischemic brains. Our findings indicate cerebral ischemia induces a marked increase in endothelial Cav-1 and Cav-2 protein levels. Importantly, genetic ablation of the Cav-1 gene in mice results in increased cerebral volume of infarction. Mechanistically, Cav-1 KO ischemic brains showed impaired angiogenesis and increased apoptotic cell death.     

丹星通络汤治疗大鼠脑缺血再灌注Bax蛋白表达的影响

目的 观察丹星通络汤对大鼠脑缺血再灌注损伤海马区细胞凋亡调控基因Bax蛋白表达的影响,探讨丹星通络汤预防与治疗大鼠脑缺血再灌注损伤的作用.方法 SD大鼠40只,随机分成假手术组、模型组、尼莫地平组、丹星通络汤小剂量组、丹星通络汤大剂量组,每组8只.采用线栓法制备大鼠大脑中动脉闭塞(MCAO)再灌注模型.HE染色检测大鼠脑组织海马区的病理学变化,免疫组织化学法和医学图像分析法检测大鼠脑组织海马区Bax蛋白的平均光密度(OD)值.结果 与模型组比较,丹星通络汤大、小剂量组大鼠脑组织海马区Bax蛋白的OD值明显减低(P＜0.05),并且丹星通络汤大剂量组与尼莫地平组相比有统计学意义(P＜0.05).结论 丹星通络汤可能通过下调Bax蛋白的表达,从而抑制脑组织的凋亡机制发挥对脑组织的保护作用.     

Reduced susceptibility to ischemic brain injury and N-methyl-D-aspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice

Cyclooxygenase-2 (COX-2), a prostanoid-synthesizing enzyme that contributes to the toxicity associated with inflammation, has recently emerged as a promising therapeutic target for several illnesses, ranging from osteoarthritis to Alzheimer's disease. Although COX-2 has also been linked to ischemic stroke, its role in the mechanisms of ischemic brain injury remains controversial. We demonstrate that COX-2-deficient mice have a significant reduction in the brain injury produced by occlusion of the middle cerebral artery. The protection can be attributed to attenuation of glutamate neurotoxicity, a critical factor in the initiation of ischemic brain injury, and to abrogation of the deleterious effects of postischemic inflammation, a process contributing to the secondary progression of the damage. Thus, COX-2 is involved in pathogenic events occurring in both the early and late stages of cerebral ischemia and may be a valuable therapeutic target for treatment of human stroke.     

脑缺血后可逆性蛋白磷酸化水平变化及电刺激对其的影响

目的研究脑缺血后神经元损伤过程中可逆性蛋白磷酸化水平变化及电刺激对其的影响。方法采用改良Longa线栓法制成永久性大脑中动脉闭塞动物模型,运用免疫荧光染色技术,检测神经颗粒素磷酸化水平(p-Ng)以及钙调神经磷酸酶(CaN)在脑缺血及电刺激不同时间内的变化情况。结果脑缺血3hp-Ng即开始增加,脑缺血1d后p-Ng水平达到高峰,缺血组为120.7±4.9,电针组为100.2±6.0(P<0.05);而缺血6hCaN开始发挥去磷酸化作用,至缺血3d后CaN免疫水平达到高峰,缺血组为44.0±3.7,电针组为48.9±3.3(P<0.05);随缺血时间延长,其免疫活性渐丧失。结论急性缺血性脑卒中,蛋白磷酸化/去磷酸化作用参与了缺血神经元损伤过程。电针刺激有可能通过维持蛋白磷酸化/去磷酸化的平衡,而发挥保护缺血神经元损伤的作用。     

神经节苷脂GM1在缺血性脑血管病中的神经保护机制

神经节苷脂GM1在脑血管病中的作用日益受到重视。已有研究证明神经节苷脂GM1对脑缺血损伤有神经保护作用。文章就神经节苷脂GM1对缺血性脑血管病神经保护作用的机制作了综述。