正加速度暴露对冠状动脉狭窄小型猪模型TNF-α和ICAM-1表达的影响

Effect of exposure to positive acceleration(+Gz) on the expression of TNF-α and ICAM-1 in swine with coronary artery stenosis

目的研究正加速度（＋Gz）暴露对冠状动脉不同程度狭窄小型猪血浆及心肌组织肿瘤坏死因子α（TNF-α）和细胞间黏附分子1（ICAM-1）表达的影响。方法健康成年雄性巴马小型猪25头，在胸腔镜直视下手术丝线永久性结扎左前降支近端建立冠状动脉狭窄模型。动物随机分为假手术组（n=5，冠脉血管未结扎）、轻度狭窄组（n=7，狭窄程度20％～49％）、中度狭窄组（n=6，狭窄程度50％～69％）和重度狭窄组（n=7，狭窄程度70％～90％）。各组小型猪进行＋Gz暴露，初始＋3Gz／60s暴露，G值增长率1G／s，每次旋转时间间隔10min，＋Gz强度最高不超过＋9Gz，分别观察各组最大＋Gz耐受值，并在其最大＋Gz暴露处理后10min留取静脉血分离血浆，双抗体夹心ABC-ELISA法测定TNF-α及ICAM-1含量。采用RT-PCR检测＋Gz暴露后各组小型猪左前壁心肌组织TNF-α和ICAM-1 mRNA的表达水平。结果与假手术组比较，轻度狭窄组最大可耐受＋Gz值变化不明显（P〉0．05），而中度狭窄组及重度狭窄组最大可耐受＋Gz值均明显下降（P〈0．05）。＋Gz暴露后，中、重度狭窄组模型猪血浆TNF-α和ICAM-1浓度及心肌组织TNF-α和ICAM-1 mRNA表达均较假手术组明显升高（P〈0．05），而轻度狭窄组与假手术组比较无明显差异（P〉0．05）。在最大加速度耐受条件下，随狭窄程度加重，中、重度狭窄组模型猪的血浆TNF-α和ICAM-1浓度及心肌组织TNF-α和ICAM-1 mRNA表达均有增加趋势。结论＋Gz暴露对冠脉不同程度血浆及心肌组织TNF-α和ICAM-1表达的影响不同，狭窄程度越重，影响越大。

Objective To study the effect of positive acceleration （＋Gz） exposure on the expression of TNF- α and ICAM- 1 in plasma and myocardium of swine with different degrees of coronary artery stenosis, and explore the effects and significance thereof in myocardial injury caused by ＋Gz stress. Methods With 25 Bama miniature swine, the proximal left anterior descending branch （LAD） was ligated permanently by using silk suture under direct thoracoscopic vision to establish different degrees of coronary artery stenosis models. Based on the degree of coronary artery stenosis, the model swine were divided into sham operation group （n=5, patent coronary artery without ligation）, mild stenosis group （n=7, the degree of stenosis 20%-49%）, moderate stenosis group （n=6, the degree of stenosis 50%-69%） and severe stenosis group （n=7, the degree of stenosis 70%-90%）. The pigs of each group were then exposed to ＋Gz environment, the initial exposure level was ＋3Gz/60s, the G was increased in 1G/s with a 10min time interval of each rotation, and the maximal ＋Gz did not exceed ＋9Gz. Then tolerance value to maximal ＋Gz acceleration of each group was then observed. Venous blood was collected from each group 10 minutes after the exposure to the maximum of ＋Gz acceleration. Contents of TNF-α and ICAM-1 in blood were determined by ABC-ELISA, and the mRNA expression levels of TNF-α and ICAM-1 in the left anterior wall of LAD were determined by RT-PCR after ＋Gz exposure. Results Compared with the sham operation group, no significant difference in tolerance value was found after subjected to maximal ＋Gz acceleration in mild stenosis group （P〉0.05）, while the values decreased significantly in moderate and severe stenosis groups （P〈0.05）. The concentrations of TNF-α and ICAM-1 in plasma and the mRNA expressions of TNF-α and ICAM-1 in myocardial tissue changed significantly in each group after ＋Gz exposure （P〈0.05）. Under the maximal acceleration condition, compared with the sham operation group, the concentrations of TNF-α and ICAM-1 in plasma and the mRNA expressions of TNF-α and ICAM-1 in myocardial tissue were increased significantly （P〈0.05） in mild, moderate and severe stenosis groups. The concentrations of TNF-α and ICAM-1 in plasma and the mRNA expressions of TNF-α and ICAM-1 in myocardial tissue presented an increasing tendency along with the aggravation ofstenosis. Conclusion The positive acceleration （＋Gz） may exert influence on the TNF-α and ICAM-1 expression in myocardial tissue and plasma of miniature swine with increasing degrees of coronary artery stenosis.