缺血预适应减轻心肌无复流和再灌注损伤的作用及机制

目的探讨缺血预适应对心肌梗死冠状动脉再通治疗后心肌无复流和再灌注损伤的影响及作用机制。方法将32只小型猪按随机数字表法分为四组，每组8只。A组为假手术组，B组为心肌梗死（MI）组，c组为缺血预适应（IPC）组，D组为IPC＋蛋白激酶A（PKA）抑制剂组H一89，Iμg／（kg．min）。采用病理学方法测定心肌无复流和心肌坏死面积，左心室、心肌缺血区和非缺血区含水量。组织学观察测定心肌细胞横切面面积和线粒体横切面面积。结果c组无复流心肌面积明显低于B组（P〈0．01），D组无复流心肌面积明显高于C组（P〈0．05）。C、D两组梗死心肌面积均明显低于B组（P均〈0．05）。C组复流区、无复流区心肌含水量相比B组有所下降（P均〈0．05）。D组各部位心肌含水量与B组比较无统计学差异（P均〉0．05）。c组复流区心肌细胞横切面面积明显低于B组（P〈0．01）。D组复流区心肌细胞横切面面积明显高于C组（P〈0．05）。c组复流区和无复流区线粒体横切面面积均小于B组（P均〈0．01）。D组复流区线粒体横切面面积明显高于c组（P〈0．05）。结论IPC可减轻急性心肌梗死（AMI）后心肌无复流和再灌注损伤，其机制与减轻心肌水肿有关，PKA通路可能在减轻心肌水肿和保护线粒体功能中起到重要作用。

Function and mechanism of ischemic preconditioning in reduction of myocardial no-reflow and reperfusion injury

Objective To explore the effect and the mechanism of ischemic preconditioning （IPC） to reduce myocardial no-reflow and reperfusion injury after revascularization of acute myocardial infarction （ AMI）. Methods A total of 32 minipigs were random- ly divided into four groups （n =8/group）. Group A was sham group, Group B was myocardial infarction group, Group C was IPC group, and Group D was IPC ＋ protein kinase A （PKA） inhibitor （H-89, 1 μg/kg·min） group. The area of no-reflow （ANR） , the area of necrosis （AN） , and the water content in left ventricle, ischemic-myocardium and non-ischemic area were determined by pathological methods. Myocardial cell cross-sectional area （CSA） and mitoehondria cross-sectional area （MSA） were evaluated by histological analysis. Results Compared with Group B, the sizes of no-reflow were reduced in Group C （P 〈 0.01 ）. The sizes of no-reflow were larger in Group D than in Group C （ P 〈 0.05 ）. The sizes of infarction were smaller in both Group C and Group D ~i . than in Group B （ P 〈 0.05 ）. Compared with Group B, the water content in reflow and no-reflow myocardlum in Group C was de- creased （ P 〈 0.05 ）. There was no difference in water content between Group D and Group B （ P 〉 0.05 ）. In group C, the sizes of CSA in the reflow area were decreased when compared with Group B （P 〈 0.01 ）. Compare with Group C, the sizes of CSA in the reflow area in Group D were increased （P 〈 0.05）. In Group C, the sizes of MSA in the reflow area and no-reflow area were both smaller than that in Group B （ P 〈 0.01 ）. The sizes of MSA in the fellow area were larger in Group D than in Group C （ P 〈 0.05 ）. Conclusion IPC can reduce myocardial no-reflow and reperfusion injury after AMI. The mechanism of cardioprotective effects may be related to the reduction of myocardial edema. PKA pathway may play an important role in reducing myocardial edema and protec- t（ng the function of mitochondria.