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。     

端粒酶逆转录酶在五羟色胺诱导的大鼠肺动脉平滑肌细胞增殖过程中的作用

目的研究端粒酶逆转录酶（TERT）在五羟色胺（5-HT）诱导的肺动脉平滑肌细胞（PASMCs）增殖过程中的作用。方法组织块法培养大鼠PASMCs。大鼠PASMCs增殖实验分别检测5-HT和反义TERT寡核苷酸对大鼠PASMCs增殖的影响。激光共聚焦显微镜检测异硫氰酸荧光素（FITC）标记的反义TERT寡核苷酸,明确反义TERT寡核苷酸在PASMCs中的分布。原位杂交实验和免疫组化实验检测反义TERT寡核苷酸和5-HT对PASMCs中TERT的mRNA和蛋白表达的影响。结果5-HT诱导大鼠PASMCs增殖实验证实5-HT在10^-9-10^-5mol／L的剂量范围内,5-HT对大鼠PASMCs的促增殖作用具有剂量依赖性。原位杂交实验和免疫组化实验证实5-HT可能直接或间接促进TERT的mRNA和蛋白表达。FITC标记的反义TERT寡核苷酸在激光共聚焦显微镜下显示,反义TERT寡核苷酸主要分布于PASMCs胞质。反义TERT寡核苷酸对大鼠PASMCs增殖抑制实验证实反义TERT寡核苷酸可以抑制5-HT诱导的大鼠PASMCs增殖,而正义TERT寡核苷酸对5-HT诱导的大鼠PASMCs增殖没有作用。原位杂交实验和免疫组化实验证实反义TERT寡核苷酸可以抑制5-HT引起的TERT的mRNA和蛋白表达增强。结论研究结果提示,TERT在5-HT诱导的PASMCs增殖过程中发挥重要作用,通过反义技术抑制TERT表达为肺动脉高压的基因治疗提供了理论基础。     

中药对缺血性脑损伤保护作用的分子机制研究进展

缺血性脑血管病是威胁人类健康最严重的疾病之一.随着医学和分子生物学技术的迅猛发展,对缺血性脑损伤的病理生理研究越来越深入,中药对缺血性脑损伤的保护机制的研究方面也从整体水平深入到了细胞和分子水平,并取得了一定的成效.现将近几年来中药对缺血性脑损伤保护作用的分子机制研究综述如下.     

转化生长因子β1与脑缺血

转化生长因子β1（TGF-β1）是一种参与缺血性脑损伤病理生理学过程的多功能细胞因子.文章就TGF-β1的生物学作用、信号调节和在缺血性脑损伤中的表达和神经保护作用机制等做了综述.     

妥泰对缺血性脑损害的保护作用研究进展

妥泰是一种新型抗癫癎药,目前已广泛应用于临床.越来越多的研究表明,其对缺血性脑损害有保护作用.文章着重介绍了妥泰对缺血性脑损伤保护作用的研究进展.     

AMPA受体与缺血性脑损伤

α 氨基 3 羟基 4异恶唑 丙酸 (AMPA)受体介导的兴奋毒性在缺血性脑损伤的发生机制中占有重要地位。文章就近年来AMAP受体结构和通道性能在缺血性脑损伤中的作用及AMPA受体拮抗剂对缺血性脑损伤保护作用的研究作了综述     

T淋巴细胞在缺血性脑损伤中的作用

缺血性脑损伤程度与卒中的病死率和致残率密切相关,如何最大程度地限制缺血性脑损伤,促进神经功能恢复,是当今神经科学领域十分关注的研究热点之一.大量研究表明,多种因素参与了缺血性脑损伤的病理过程.其中,T淋巴细胞介导的免疫炎症反应在缺血性脑损伤中的作用越来越受到关注,文章主要综述了T细胞在缺血性脑损伤中的作用.     

促红细胞生成素对脑损伤的保护作用

促红细胞生成素 (EPO)具有神经保护作用 ,在缺血性脑损伤和蛛网膜下腔出血等中枢神经系统损伤中发挥保护作用的机制有多种 ,如抗细胞凋亡和清除自由基等。此外 ,EPO能通过与特异性受体结合透过血脑屏障 ,这是许多神经营养因子所不具备的优势。因此 ,其临床应用前景看好。     

T淋巴细胞在缺血性脑损伤中的作用

缺血性脑损伤程度与卒中的病死率和致残率密切相关,如何最大程度地限制缺血性脑损伤,促进神经功能恢复,是当今神经科学领域十分关注的研究热点之一.大量研究表明,多种因素参与了缺血性脑损伤的病理过程.其中,T淋巴细胞介导的免疫炎症反应在缺血性脑损伤中的作用越来越受到关注,文章主要综述了T细胞在缺血性脑损伤中的作用.     

脑缺血与内源性神经保护

脑缺血后一系列损伤级联反应既可启动缺血性脑损伤的诸多环节 ,又可启动内源性神经保护机制 ,增强内源性神经保护效应对限制缺血损伤和促进可逆性受损的神经组织的修复和再生至关重要。文章就近年来内源性神经保护的机制和内源性神经保护增效剂方面的研究作了综述。     

Mechanisms of ischemic brain injury

Stroke is the third leading cause of death and the leading cause of long-term disability in the United States. Approximately 80% of all strokes are ischemic and there are limited therapies approved for the treatment of acute ischemic stroke. Understanding the mechanisms of ischemic brain damage is necessary for the development of innovative treatment strategies. In this review, we discuss the hemodynamic and molecular mechanisms of ischemic brain damage and the potential therapeutic strategies, including reperfusion and primary and secondary neuroprotection, and strategies for recovery of function, such as neural plasticity and stem cell transplantation. The effective treatment of ischemic stroke is likely to result from a combination of therapeutic modalities aimed at different mechanisms of ischemic brain damage and delivered at specific times after acute cerebral ischemia.     

About spread of local cerebral hemorheological disorders to whole body in critical care patients

PURPOSE: The aim of the present pathophysiological studies was elucidation of the feasible mechanism of spread of the blood rheological disorders from the cerebral to systemic circulation, and vice versa. METHODS: The investigation was carried out in the critical care patients with the brain tissue damage related to stroke (cerebral ischemic infarcts as well as parenchymatous and subarachnoid hemorrhages). The applied diagnostic techniques provided us with valid and quantitative data revealing the degree of the red blood cell aggregability, the value of local hematocrit, and the blood plasma viscosity in the cerebral and systemic circulation. In addition, rabbits experiments were carried out for analysis of the hemorheological disorders associated with the brain damage. RESULTS: Despite the local character of the patients primary brain damage, the hemorheological disorders were found regularly spread not only over the cerebral hemispheres, but even also the systemic circulation. Under such conditions they might cause the generalized brain tissue damage and play significant role in the subsequent damage-cascade of the whole brain. In addition, the rabbits experiments demonstrated pronounced hemorheological disorders in the cerebral cortex capillaries: increase of their numbers with RBC enhanced aggregation and blood stasis, as well as with lowering of the RBC deformability in the narrow capillary lumina. These changes befell simultaneously with increase of water contents in the cerebral tissue evidencing for edema development in the brain. CONCLUSION: Local cerebral hemorheological disorders might spread over the whole brain via the systemic circulation, thus promoting a generalized brain damage and being responsible for the critical state of the patients.     

Effects of blockade of cerebral lymphatic drainage on cerebral ischemia after middle cerebral artery occlusion in rats

This experiment aimed to investigate the effects of blockade of cerebral lymphatic drainage on cerebral ischemic damage. Seventy six Wistar rats were divided randomly into middle cerebral artery occlusion (MCAO) group and MCAO plus cerebral lymphatic blockade (MCAO+CLB) group for the experiment. The contents of water and electrolytes, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in the ischemic brain tissue were detected at 24, 48 and 72 hours after the operation. The morphologic examination was also performed. In MCAO group, contents of water, sodium and calcium in the ischemic brain tissue increased significantly at any time after the operation. The SOD activity decreased while the MDA content increased markedly. The morphologic findings showed severe damage of ischemic brain tissue and neurons. In MCAO+CLB group, the above parameters were altered more obviously. The present observation suggests that blockade of cerebral lymphatic drainage may deteriorate ischemic brain damage after MCAO.     

脑蛋白水解物-Ⅰ防治C57小鼠脑衰老的作用机制

目的 研究脑蛋白水解物(CH)-Ⅰ延缓D-半乳糖(D-gal)致C57小鼠衰老的作用机制。方法 C57/BL6N小鼠随机分为对照组、模型组、CH-Ⅰ低剂量组和CH-Ⅰ高剂量组,皮下注射D-gal以诱导衰老模型,给药组腹腔注射CH-Ⅰ。Morris水迷宫实验检测小鼠的学习和记忆能力,苏木素-伊红(HE)染色观察神经元的形态结构,Western印迹检测脑源性神经营养因子(BDNF)、信号传感器和转录激活因子(STAT)3/磷酸化(p)-STAT3和端粒酶逆转录酶(TERT)的表达,PCR-酶联免疫吸附试验(ELISA)检测端粒酶活性的表达。结果 与对照组相比,模型组学习记忆能力显著下降(P<0.01),海马神经元损伤明显增加(P<0.01),端粒酶活性明显降低(P<0.01),BDNF、TERT和p-STAT3表达水平下降(P<0.01)。而给予不同浓度的CH-Ⅰ预处理后,衰老小鼠的学习记忆能力障碍得到改善(P<0.05),海马神经元损伤显著下降(P<0.05),并且CH-Ⅰ低、高浓度均可以显著提高小鼠海马组织的端粒酶活性(P<0.05),上调BD...     

体外反搏在缺血性脑血管病康复中的作用与机制

尽管治疗手段在发展,缺血性脑血管疾病仍是致死和致残的主要原因。体外反搏可增加脑血流灌注,可降低缺血区域的神经细胞损害。国内体外反搏治疗缺血性脑血管疾病的临床研究结果提示该方法有效、安全及不良反应轻微,但由于大多存在研究设计的缺陷,未能提供充足的临床证据。国外有限的研究提示了体外反搏对缺血性脑血管疾病具有良好的治疗效果。体外反搏对脑血管病的治疗机制尚未完全阐明,可能与增加脑部血流灌注,增加侧支循环形成,改善血管内皮功能及促进血管新生和脑重塑有关。体外反搏可能是一种很有潜力的缺血性脑血管疾病的治疗和辅助治疗手段,但期待更多前瞻性、随机对照临床试验的证实。     

尼莫地平对脑出血后缺血性脑损害保护作用的研究

目的探讨脑出血后继发性缺血性脑损害机制以及尼莫地平对脑出血后继发性缺血性脑损害的保护作用。方法60例脑出血患者随机分为尼莫地平组(30例)与常规治疗组(30例),在治疗前后用单光子发射型计算机断层显像(SPECT)观察原发灶缺血体积,血肿周围及脑部其他区域的局部脑血流量(rCBF)变化。结果尼莫地平组和常规治疗组治疗后原发灶缺血的体积明显缩小,原发灶缺血体积减少值尼莫地平组明显高于常规治疗组(P<0.01)。治疗后原发灶及远隔部位缺血灶rCBF增加值尼莫地平组明显高于常规治疗组(P<0.01)。结论脑出血后血肿周围及远隔区域可出现广泛的rCBF下降,血肿周围可能存在缺血半暗带。尼莫地平治疗脑出血有确切疗效,可改善局部脑缺血。     

尼莫通对脑缺血后迟发性神经元损伤保护作用的实验研究

目的　研究脑缺血再灌注后迟发性神经元坏死（ Ｄ Ｎ Ｄ ）的病理学改变及测定病灶区 Ｃａ２ ＋ 含量的变化,并观察尼莫通对 Ｄ Ｎ Ｄ 的保护作用。方法　制作大鼠一侧大脑中动脉缺血再灌注模型。结果　当脑缺血 ６ ｈ 以上再灌流时 Ｄ Ｎ Ｄ 现象明显。结论　早期应用尼莫通治疗可使 Ｄ Ｎ Ｄ 减轻,起到神经元保护作用。