Choi Soo Joo, Kim Myung Hee, Lim Seung Woon, Gwak Mi Sook
Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
J Korean Med Sci. 2005 Feb;20(1):113-20. doi: 10.3346/jkms.2005.20.1.113.
Apoptosis is a programmed, physiologic mode of cell death that plays an important role in tissue homeostasis. As for the central nervous system, ischemic insults can induce pathophysiologic cascade of apoptosis in neurophils. Impairment of astrocyte functions during brain ischemia can critically influence neuron survival by neuronglia interactions. We aimed to elucidate the protective effect of ketamine on apoptosis by energy deprivation in astrocytes. Ischemic insults was induced with iodoacetate/ carbonylcyanide m-chlorophenylhydrazone (IAA/CCCP) 1.5 mM/20 microm or 150 microm/2 microm for 1 hr in the HTB-15 and CRL-1690 astrocytoma cells. Then these cells were reperfused with normal media or ketamine (0.1 mM) containing media for 1 hr or 24 hr. FITC-annexin-V staining and propidium iodide binding were determined by using flow cytometry. Cell size and granularity were measured by forward and side light scattering properties of flow cytometry system, respectively. An addition of ketamine during reperfusion increased the proportion of viable cells. Ketamine alleviated cell shrinkage and increased granularity during the early period, and ameliorated cell swelling during the late reperfusion period. Ketamine may have a valuable effect on amelioration of early and late apoptosis in the astrocytoma cells, even though the exact mechanism remains to be verified.
细胞凋亡是一种程序性的生理细胞死亡模式,在组织稳态中发挥重要作用。至于中枢神经系统,缺血性损伤可诱导神经细胞发生细胞凋亡的病理生理级联反应。脑缺血期间星形胶质细胞功能的损害可通过神经元与神经胶质细胞的相互作用严重影响神经元的存活。我们旨在阐明氯胺酮对星形胶质细胞能量剥夺诱导的细胞凋亡的保护作用。在HTB - 15和CRL - 1690星形细胞瘤细胞中,用1.5 mM/20微摩尔或150微摩尔/2微摩尔的碘乙酸盐/羰基氰化物间氯苯腙(IAA/CCCP)诱导缺血性损伤1小时。然后将这些细胞用正常培养基或含氯胺酮(0.1 mM)的培养基再灌注1小时或24小时。通过流式细胞术测定FITC - 膜联蛋白V染色和碘化丙啶结合情况。分别通过流式细胞术系统的前向和侧向光散射特性测量细胞大小和粒度。再灌注期间添加氯胺酮增加了活细胞的比例。氯胺酮在早期减轻了细胞收缩并增加了粒度,在再灌注后期改善了细胞肿胀。氯胺酮可能对改善星形细胞瘤细胞的早期和晚期凋亡具有重要作用,尽管确切机制仍有待验证。