中国临床康复2004,Vol.8Issue(16):3174-3175,2.
肌苷对脑缺血再灌注后神经细胞凋亡和细胞色素C基因表达的影响
Effects of inosine on apoptosis and expression of cytochrome CmRNA in neurons after cerebral ischemia-reperfusion in rats
摘要
Abstract
BACKGROUND: The release of cytochrome C (Cyt C) from mitochondria is a critical step in the apoptosis process. Inosine could play a certain inhibiting role in neuronal apoptosis after cerebral ischemic injury, but its mechanism is not known thoroughly.OBJECTIVE: To investigate the effects of inosine on neuronal apoptosis and expression of cytochrome C mRNA in rats after focal cerebral ischemic reperfusion.DESIGN: A randomized controlled experimental research.SETTING and MATERIALS: This experiment was carried out in the Institute of Cerebrovascular Diseases, Medical College of Qingdao University and the Key Laboratory of the Prevention and Cure of Cerebrovascular Diseases of Shandong Province. Sixty-eight adult healthy female SD rats,weighting 230 - 270 g, clearing grade, were purchased from Shanghai Experimental Animal Center of Chinese Academy of Science.INTERVENTION: The model of ischemic reperfusion in SD rats was established by middle cerebral artery occlusion with a nylon monofilament suture. The rats were randomly divided into treatment group(32 rats injected with inosine intraperisoneally, 100 mg/kg) and control group(32 rats injected with saline solution intraperisoneally). Each group was then randomly divided into eight subgroups with 4 rats in each at 2 hours, 6, 12, 24 hours,and 2, 3, 7, 14 days of reperfusion after 1.5 hours' ischemia. The other 4rats served as sham-operation group. In situ hybridization was performed to examine the expression of cytochrome C mRNA while terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-label ing(TUNEL) staining was made to characterize apoptosis.MAIN OUTCOME MEASURES: Neuronal apoptosis and expression of cytochrome C mRNA in brain tissues after cerebral ischemic reperfusion.RESULTS: TUNEL-positive cells were observed at 2 hours of reperfusion, the number increased gradually and peaked at 1 day and 2 days of reperfusion in the cortex and striatum, respectively, then reduced to the level of sham-operation group at 14 days. In inosine group, the number of TUNEL-positive cells decreased during 12 hours-7 days of reperfusion compared to that of the control group. Cytochrome C mRNA was expressed in the cortex and striatum of ischemic hemisphere as early as 2 hours of reperfusion, reached a peak at 12hours and 1 day in the cortex and striatum, respectively. Inosine treatment could diminish the cytochrome C mRNA expression at 12 hours to 7 days in the cortex and 12 hours to 14 days in the striatum, respectively.CONCLUSION: Inosine can exert a protective effect on nerves by inhibiting apoptosis and related mRNA expression. Therefore, it may be a potential compound in treating cerebrovascular diseases.关键词
脑缺血/病理生理学/肌苷/治疗应用/基因表达/细胞色素C分类
医药卫生引用本文复制引用
李琴,毕明俊,张红,郑青立,郭云良..肌苷对脑缺血再灌注后神经细胞凋亡和细胞色素C基因表达的影响[J].中国临床康复,2004,8(16):3174-3175,2.基金项目
山东省自然科学基金资助项目(Y2001C04) (Y2001C04)