羟乙基淀粉对大鼠心肌缺血再灌注后无复流的影响

 目的: 探讨羟乙基淀粉(HES 130/0.4)对大鼠心肌缺血再灌注中无复流现象的影响及机制。方法: 36只SD大鼠随机分为缺血-再灌注组(IR组),生理盐水组(NS-IR组),羟乙基淀粉组(HES-IR组)和假手术组(sham组)。NS-IR和HES-IR组在缺血30 min时分别静注生理盐水和HES 130/0.4,再灌注180 min后以Evans blue、Thilflavin S和TTC染色测定心肌梗死面积与无复流范围,同时检测心肌肌酸激酶同工酶(CK-MB)、心肌肌钙蛋白I(cTnI)含量和髓过氧化物酶(MPO)活性。培养心肌微血管内皮细胞,随机分为正常对照组(Con组),缺氧-复氧组(H/R组),生理盐水组(NS-H/R组)和羟乙基淀粉组(HES-H/R组),以缺氧复氧法模拟急性缺血再灌注,测定游离钙离子浓度、细胞活力和凋亡率。结果: HES-IR组大鼠心肌梗死面积、无复流范围、心肌酶CK-MB、cTnI和MPO与IR组相比均减少(P<0.05)。HES-H/R组细胞内游离钙离子浓度和细胞凋亡率较H/R组亦明显减少(P<0.05),而细胞活力增高(P<0.05)。结论: HES 130/0.4能改善心肌缺血-再灌注后的无复流现象,其机制不仅涉及对中性粒细胞激活、浸润的抑制,还与减轻内皮细胞钙超载有关。

Effects of HES 130/0.4 on no-reflow after myocardial ischemia-reperfusion injury in rats

AIM: To observe the effects and mechanisms of hydroxyethylstarch(HES) 130/0.4 on no-reflow phenomenon after myocardial ischemia-reperfusion in rats. METHODS: SD rats were randomly divided into 4 groups:sham operation group, ischemia-reperfusion(IR, treated with normal saline) group, normal saline ischemia-reperfusion(NS-IR, treated with NS) group and HES ischemia-reperfusion(HES-IR, treated with HES) group. Myocardial infarct size and no-reflow range were determined by staining methods, and the activities of myocardial enzymes(CK-MB, cTnI and MPO) were measured. Meanwhile, cardiac microvascular endothelial cells of the rat were cultured and divided into 4 groups:control group, hypoxia/reoxygenation(H/R) group, NS-H/R group and HES-H/R group. Acute ischemia reperfusion models were simulated, and the concentration of calcium ions was measured. The relative cell activity was evaluated by CCK-8 assay, and the apoptotic rate was detected by flow cytometry. RESULTS: In HES-IR group, the myocardial infarct size, the no-reflow zone, CK-MB, cTnI and MPO activity were all significantly lower than those in IR group(P<0.05). In microvascular endothelial cells, the concentration of calcium ions and the apoptotic rate in HES-H/R group were significantly decreased, while the relative cell activity increased compared with H/R group(P<0.05). CONCLUSION: HES reduces no-reflow in acute myocardial ischemia-reperfusion. The mechanism may be involved in the inhibition of both the infiltration of neutrophils and the calcium overload of endothelial cells.