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降钙素基因相关肽和BIBN4096BS对麻醉大鼠心肌缺血的作用
AIM: The cardioprotective effect of calcitonin generelated peptide (CGRP) was investigated in an ischemia rat model. METHODS: Ischemia-reperfusion injury was provoked by 60 min left main coronary artery occlusion followed by 60 min of reperfusion in anesthetized rats. The transverse slices of ventricles were stained by 2,3,5-triphenyltetrazolium chloride to determine the infarct area. Plasma creatine phosphokinase levels weredetermined by means of a creatine phosphokinase (CPK)kit. A radioimmunoassay was used to determine plasma CGRP levels. RESULTS: Intravenous infusion of CGRP (1 nmol· kg- 1·h-1) 10 min before occlusion until the end of reperfusion reduced infarct size by 89 % ±5 %. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase.Infusion of the same dose of CGRP commehcing from the start of reperfusion until its end induced a 40 % ± 3 %reduction of the infarct size. The cardioprotective effects of CGRP were blocked by the novel CGRP antagonist BIBN4096BS (20 nmol· kg-1 · h-1 ). Although cardiac ischemia resulted in an almost 50 % increase in plasma CGRP levels in blood sampled from right cardiac ventricle, intravenous infusion of the CGRP antagonist BIBN4096BS before occlusion until the end of reperfusion had no statistically significant effect on the infarct size.CONCLUSION: The present study demonstrates that CGRP is a potent myocardial protective substance.
关键词: 降钙素基因相关肽 BIBN4096BS 心肌梗死 再灌注损伤