预处理对大鼠缺血冠脉等组织t-PA、PAI-1基因表达的影响

Changes in t-PA, PAI-1 Gene Expression of Coronary Arteries with Preconditioning in Acute Myocardial Infarction Rat

采用Northern印迹杂交、斑点杂交、原位杂交技术和发包庇物显色测定方法研究急性心肌缺血大鼠冠脉等组织t－PA、PAI－1基因表达和t－PA活性变化、缺血预处理对这些改变的影响。结果表明：（1）缺血组冠脉等组织t－PA活性明显低于对照组，预处理组高于缺血组，3组组间比较均P＜0．01。（2）Northern和斑点杂交显示急性心肌梗塞时t－PA、PAI－1mRNA表达均增高，分别为对照大鼠的1．2和4．6倍，预处理组PAI－1mRNA表达明显降低，t－PAmRNA表达与缺血组近似。（3）心肌组织原位杂交检测到t－PA、PAI－1mRNA主要分布在冠脉血管，尤其集中于内皮细胞。上述结果提示，心肌缺血损伤时t－PA、PAI－1mRNA均异常表达，其中PAI－1的高表达是心肌缺血时纤溶活性降低的主要原因，预处理恢复组织中t－PA活性与PAI－1mRNA表达减少密切相关。以上结果为预处理保护机制研究提供了新的资料。

The changes of t-PA, PAI-1 gene expression and t-PA activity were investigated incoronary arteries of Acute Myocardial Infarction (AMI) rat by nucleic ac1d molecular hy-bridization and spectrophotometric assay. The effect of preconditioning on t-PA and PAI-1was observed in this model. The results indicated that: (l) Tissue t-PA activity in ischemiawas significantly decreased than that in control (P<O. O1 ). t-PA activity was obviously in-creased in preconditioning group (PrO. O1 compared with ischemia group). (2) t-PA andPAl-1 mRNA expression in ischemia were higher than that in control, especial1y PAI-1 4. 6times higher than that in control), while PAI-1 expression lower in preconditioning rat. (3)In situ hybridization showed t-PA and PAI-1 were primarily expressed by endothelial cells invessels of rat heart. These data suggested that abnormal expression of PAI-1 and t-PA wasinvolved in AMI. This fibrinolytic depress was associated with high PAI-1 expression- Pre-conditioning may be effective to protect myocardium through decreasing PAI-l mRNA ex-pression.