摘要
目的:探讨大鼠心肌缺血再灌注(ischemiareperfusion,IR)不同时相Fas表达、心肌细胞凋亡指数、天冬氨酸特异的半胱胺酸蛋白酶3(caspase-3)活性变化规律,探讨对其进行干预的可能性。方法:实验选用Wistar大鼠116只,随机设立IR组、治疗组和对照组并分设缺血30min后再灌注1,3,6,12及24h5个时相点。治疗组于再灌注开始时尾静脉注射caspase-3抑制剂Ac-DEVD-CHO。分别检测Fas表达、心肌细胞凋亡指数、caspase-3活性和心肌梗死范围。结果:Fas表达、心肌细胞凋亡指数与caspase-3活性随心肌再灌注不同时相而变化,Fas表达于再灌注6h最高(1.72±0.16),心肌细胞凋亡指数与caspase-3活性犤(34.83±9.35)%,(22.34±4.50)nkat〗于再灌注12h最高,其后基本维持在平台状态;心肌梗死范围随IR时间逐渐增加,至24h仍未见下降趋势。治疗组上述指标虽也明显增高,除Fas表达外均比IR组明显减小(t=2.990～9.596,P<0.05～0.01)。结论:Fas表达增高激活caspase-3导致心肌细胞凋亡是心肌缺血再灌注损伤形成的机制之一,Ac-DEVD-CHO减轻再灌注损伤的机制可能是其抑制心肌细胞凋亡。
AIM: To discuss the alternating regularities of the Fas expression, apoptosis index (AI) of myocardium and caspase 3 activity in different phase in rats with myocardium ischemia reperfusion (IR), so as to explore the probability of intervention. METHODS: Totally 116 Wistar rats are randomly divided into IR group, treatment group and control group, and there were 5 phases of 30 minute ischemia 1, 3, 6, 12 and 24 hour reperfusion. The rats in the treatment group received injection of caspase 3 inhibitor Ac DEVD CHO to the caudal vein at the beginning of reperfusion. The Fas expression, AI and caspase 3 activity and myocardial infarction range were detected in all groups. RESULTS:The Fas expression, caspase 3 activity and AI changed with the alteration of time of reperfusion, and the Fas expression reached the peak value (1.72±0.16) 6 hours after reperfusion, AI and caspase 3 were the highest 12 hours after reperfusion [(34.83±9.35)%and (22.34±4.50) nkat], and then maintained at the platform status; myocardial infarction range was increased with the elongation of IR time, and had no decreasing tendency until 24 hours after reperfusion. All the above mentioned indexes were obviously increased in the treatment group, but obviously decreased as compared with those in the IR group expect for the Fas expression (t=2.990 to 9.596, P< 0.05 to 0.01). CONCLUSION: The activation of caspase 3 induced by increase of Fas expression can result in myocardium apoptosis, which is one of the mechanisms for the formation of myocardium ischemia reperfusion injury. Ac DEVD CHO is effective in reducing myocardial reperfusion injury, which may be attributed to the attenuation of cardiomyocyte apoptosis.
出处
《中国临床康复》
CSCD
2004年第27期5828-5829,i001,共3页
Chinese Journal of Clinical Rehabilitation
