预缺氧对缺氧-复氧性冠状血管损伤的保护作用与机制

摘要

Whether myocardial ischemic preconditioning ha s direct protective effects on ischemia/reperfusion-induced coronary dysfunctio n is undetermined yet. the possible protecting effect of hypoxic preconditioning on hypoxia-reoxygenation(H-R)-induced vascular injury in isolated coronary v essel was investigated.The study included the following four experiments:①The i s olated rabbits coronary arterial rings were examined for their vasodilating fu nction.It was shown that HPC had direct protective effects on H-R-induced coro nary vasodilating dysfunction.This effect could be antagonized by 8-PT,an adeno sine blocker,but not by L-NAME.②H-R treatment could obviously increase the NO S activity and NO content of vascular tissue,while HPC could significantly reduc e the extent of increased NOS activity and NO content induced by H-R.③By using RT-PCR technique to detect the expression of iNOS mRNA,it was found that there was no iNOS mRNA expression under normal condition.However,H-R treatment incre ased greatly the expression of iNOS mRNA while HPC decreased the expression. ④EM observation confirmed the protective effect of HPC on H-R-induced ultrast ructural changes.These results suggest that HPC has protective effects on H-R- induced coronary vascular injury and adenosine plays an important role in the pr otective mechanism.H-R increases the expression of iNOS mRNA in vascular tissue and thereby injures the vessel,while HPC exhibits the protective role by decre asing the expression of iNOS and the NO content.These findings provide a theoret ical evidence for the diagnosis of sudden death.%心脏预缺血对缺血-再灌注时冠状血管功能障碍是否 有直接的保护效应，尚少证据。在离体冠脉血管观察了预缺氧(HPC)对缺氧-复氧(H-R)性血 管损伤的保护作用。实验分四部分：①利用兔离体冠脉血管环的微量生物反应测定法，证实 HPC对H-R引起的血管舒张功能障碍有直接保护作用，此作用可被腺苷阻断剂8-PT消除，但 不能被L-NAME消除；②测定血管组织NO含量和NOS活性，发现H-R处理可明显增高血管组织 NOS活性和NO含量，HPC能减轻H-R引起的NOS活性和NO含量的增高程度；③应用反转录-聚合 酶链反应(RT-PCR)方法检测血管组织iNOS mRNA表达的变化，发现正常时无表达，H-R处理 使表达增高，而HPC则可使表达下降；④电镜超微结构观察，证实对引起的冠脉血管超微结 构变化有保护作用。以上结果提示，预缺氧对缺氧-复氧性冠状血管损伤有直接保护作用， 腺苷在保护机制中起重要作用；缺氧-复氧可使离体冠脉血管组织iNOS mRNA表达增加，NOS 活性和NO含量增高，从而造成损伤，而预缺氧可减少iNOS mRNA的表达，降低NOS活性和NO含 量而起到保护作用，为法医病理学猝死的鉴定提供理论依据。