吗啡胸段硬膜外给药对急性心肌缺血诱发大鼠肺组织肿瘤坏死因子-α表达的影响

目的 观察急性心肌缺血大鼠肺组织中肿瘤坏死因子-α(TNF-α)的表达变化以及吗啡硬膜外给药的干预效应.方法 将健康成年雄性SD大鼠18只随机分为假手术组(S组)、结扎冠状动脉(冠脉)缺血组(CAO组)和吗啡预处理组(M组),每组6只.S组动物仅开胸,不结扎左冠脉前降支;CAO组动物开胸后结扎左冠脉前降支;M组动物在结扎左冠脉前降支前15 min经硬膜外注射吗啡60μg/kg.各组在开胸或扎闭左冠脉前降支后3 h开胸取右肺下叶,采用免疫组化、酶联免疫吸附法(ELISA)检测肺组织中TNF-α表达变化.结果 免疫组化结果显示,与S组比较(8.68±0.29,1.609±0.050),CAO组(24.55±6.25,1.844±0.027)和M组(11.60±1.21,1.733±0.027)气管TNF-α阳性单位及平均吸光度(A)值均明显升高,而M组较CAO组明显降低,差异均有统计学意义(P均<0.01).ELISA结果显示:CAO组[(221.58±5.23)ng/L]和M组[(103.45±4.56)ng/L3肺组织TNF-α阳性免疫反应物质的表达水平均高于S组E(47.14±1.36)ng/L),且M组显著低于CAO组(P均<0.01).结论 急性心肌缺血能通过神经机制介导肺脏TNF-α表达上调;阿片类物质及其受体机制参与了机体内心脏伤害性神经信号转导的调节.

Effects of epidurally administration of morphine at thoracic level on expression of tumor necrosis factor-α in the lungs in acute myocardial ischemia in rats

Objective To investigate the expression of tumor necrosis factor-α (TNF-α) in lungs following coronary artery occlusion (CAO) and the effect of morphine pretreatment via epidural administra-tion on its expression in the rats. Methods Eighteen adult healthy male Sprague-Dawley (SD) rats were randomly divided into sham operation group (S group), CAO group and morphine pretreatment group (M group), with 6 in each group. In S group the left anterior descending branch of coronary artery was not occluded. In CAO group the left anterior descending branch of coronary artery was occluded. In M group the rats were pre-treated with morphine 60 μg/kg by epidural injection 15 minutes before CAO. The right lung was harvested 3 hours after CAO. The expression of TNF-α in lungs was assessed with immuno-histochemistry and enzyme linked immunosorbent assay (ELISA). Results The immunohistochemistry results showed, compared with S group (8. 68±0. 29, 1. 609 ± 0. 050), the positive unit and average light density of TNF-α in CAO group (24. 55±6. 25, 1. 844±0. 027) and M group (11.60±1.21, 1. 733±0. 027) were higher significantly, while they were lower significantly in M group compared with CAO group (all P<0. 01). ELISA results showed the level of TNF-α in the lung was significantly higher in CAO group [(221.58±5. 23) ng/L] and M group [(103. 45±4. 56) ng/L] than that in S group [(47. 14±1.36) ng/L],while it was significantly lower in M group compared with CAO group (all P<0. 01). Conclusion Acute myocardial ischemia could cause up-regulation of TNF-a in lungs, which is likely to be mediated by neural mechanisms. Opioid and its receptors in spinal cord might be involved in modulation of inflammatory reaction in the lung after acute coronary ischemia.