缺血性脑卒中的抗凋亡治疗
凋亡是由细胞内特定的基因所操纵、调控的一种细胞‘自杀’行为，其不仅参与了正常的生理过程,还介导了如Parkinson病、Alzheimer病及心、脑血管病等诸多疾病的病理过程。细胞凋亡与缺血性脑卒中的神经元损伤密切相关。在脑缺血急性期，缺血中心区的神经元以坏死为主，半暗带的迟发性神经元死亡(DND)则以凋亡为主；在缺血后再灌注期，神经元的死亡则大多是凋亡形式。而缺血性脑卒中的主要治疗目的就是挽救缺血性半暗带。
凋亡的主要形态学及生化特征为：核染色质固缩、胞浆膜鼓泡、胞浆浓缩、凋亡小体的出现以及由于DNA降解电泳中呈现特征性DNA ladder。
缺血性脑卒中确切的神经元凋亡机制尚不清楚，目前认为可能与兴奋性氨基酸、Ca2+超载、自由基的毒性作用、神经元生存环境的改变、线粒体功能障碍及凋亡调控基因的激活等因素有关。
缺血性脑损伤所致的细胞凋亡大致分为三个阶段：启动期、效应期和降解期。凋亡的诱导是一个复杂的调节过程，并能为许多细胞外因子的刺激所抑制。目前常用的抗凋亡措施主要有：Ca2+拮抗剂、自由基清除剂、EAAs受体拮抗剂、神经营养因子、缺血预处理、亚低温治疗、Caspase蛋白酶抑制剂及转基因治疗等。由于药物治疗时间窗、药物剂量及毒副反应、样本量、病例选择、种属差异及疗效判断标准等因素的影响，缺血性脑卒中的许多抗凋亡治疗在动物实验和临床研究方面存在较大差异，但我们相信，抗凋亡治疗一定会为缺血性脑血管的治疗开辟一片广阔的天地。
, 百拇医药
Anti-apoptotic therapies for ischemic cerebral stroke
DING Xinsheng,The 1st Affiliated Hospital of Nanjing Medical University
Apoptosis is a cell-suicide program mediated by some specific endogenous genes. It has been implicated not only in general celluar biology, but also in the pathophysiology of some disorders such as Parkinson disease, Alzheimer disease, cardiovascular disease and cerebrovascular disease, etc. Close correlation has been documented between apoptosis and ischemic neuronal injury. In acute cerebral ischemia, it has been reported that necrosis is a common cause of neuronal death in ischemic core, and apoptosis plays an important role in delayed neuronal death in ischemic penumbra. During reperfusion, however, injured neurons mainly suffer from apoptosis. It is well known that the main purpose for the treatment of ischemic cerebral stroke is to salvage those injured neurons in penumbra.
, 百拇医药
Apoptosis is characterized by some morphological and biochemical alterations including shrinkage and condensation of nuclear chromatin, blebbing of cytoplasmic membrane, condensation of cytoplasm and formation of apoptotic bodies. Specific DNA ladder can be shown on agarose gels because of the cleavage of DNA into fragmentations.
The actual apoptotic mechanism for injured neurons in cerebral ischemia remains unclear. Evidences show that excitotoxcities of excited amino acid and free radical, Ca2+ overload, environmental alteration of neurons, mitochondrial dysfunction and activation of some apoptotic genes may be involved in it.
, 百拇医药
There are three consecutive stages in the apoptotic process of ischemic neurons including initiation, execution and degradation. Apoptosis is a very complicated process, which can be prohibited by lots of extracellular factors. Some measures have been reported to protect ischemic neurons from apoptosis, such as Ca2+ antagonists, free radical scavengers, EAA antagonists, neurotrophic factors, ischemic preconditioning, hypothermia, Caspase’s inhibitor and transgenic therapy. Although striking discrepancies have been shown between animal models and clinical trials for anti-apototic therapy in cerebral ischemia as a result of different therapeutic time windows and doses, toxic and adverse effects, improper cases and sample sizes as well as different species and evaluations of efficacy. However, we hold that these strategies should have a prosperous future in cerebrovascular disease therapy., 百拇医药(丁新生)
凋亡的主要形态学及生化特征为：核染色质固缩、胞浆膜鼓泡、胞浆浓缩、凋亡小体的出现以及由于DNA降解电泳中呈现特征性DNA ladder。
缺血性脑卒中确切的神经元凋亡机制尚不清楚，目前认为可能与兴奋性氨基酸、Ca2+超载、自由基的毒性作用、神经元生存环境的改变、线粒体功能障碍及凋亡调控基因的激活等因素有关。
缺血性脑损伤所致的细胞凋亡大致分为三个阶段：启动期、效应期和降解期。凋亡的诱导是一个复杂的调节过程，并能为许多细胞外因子的刺激所抑制。目前常用的抗凋亡措施主要有：Ca2+拮抗剂、自由基清除剂、EAAs受体拮抗剂、神经营养因子、缺血预处理、亚低温治疗、Caspase蛋白酶抑制剂及转基因治疗等。由于药物治疗时间窗、药物剂量及毒副反应、样本量、病例选择、种属差异及疗效判断标准等因素的影响，缺血性脑卒中的许多抗凋亡治疗在动物实验和临床研究方面存在较大差异，但我们相信，抗凋亡治疗一定会为缺血性脑血管的治疗开辟一片广阔的天地。
, 百拇医药
Anti-apoptotic therapies for ischemic cerebral stroke
DING Xinsheng,The 1st Affiliated Hospital of Nanjing Medical University
Apoptosis is a cell-suicide program mediated by some specific endogenous genes. It has been implicated not only in general celluar biology, but also in the pathophysiology of some disorders such as Parkinson disease, Alzheimer disease, cardiovascular disease and cerebrovascular disease, etc. Close correlation has been documented between apoptosis and ischemic neuronal injury. In acute cerebral ischemia, it has been reported that necrosis is a common cause of neuronal death in ischemic core, and apoptosis plays an important role in delayed neuronal death in ischemic penumbra. During reperfusion, however, injured neurons mainly suffer from apoptosis. It is well known that the main purpose for the treatment of ischemic cerebral stroke is to salvage those injured neurons in penumbra.
, 百拇医药
Apoptosis is characterized by some morphological and biochemical alterations including shrinkage and condensation of nuclear chromatin, blebbing of cytoplasmic membrane, condensation of cytoplasm and formation of apoptotic bodies. Specific DNA ladder can be shown on agarose gels because of the cleavage of DNA into fragmentations.
The actual apoptotic mechanism for injured neurons in cerebral ischemia remains unclear. Evidences show that excitotoxcities of excited amino acid and free radical, Ca2+ overload, environmental alteration of neurons, mitochondrial dysfunction and activation of some apoptotic genes may be involved in it.
, 百拇医药
There are three consecutive stages in the apoptotic process of ischemic neurons including initiation, execution and degradation. Apoptosis is a very complicated process, which can be prohibited by lots of extracellular factors. Some measures have been reported to protect ischemic neurons from apoptosis, such as Ca2+ antagonists, free radical scavengers, EAA antagonists, neurotrophic factors, ischemic preconditioning, hypothermia, Caspase’s inhibitor and transgenic therapy. Although striking discrepancies have been shown between animal models and clinical trials for anti-apototic therapy in cerebral ischemia as a result of different therapeutic time windows and doses, toxic and adverse effects, improper cases and sample sizes as well as different species and evaluations of efficacy. However, we hold that these strategies should have a prosperous future in cerebrovascular disease therapy., 百拇医药(丁新生)