缺氧诱导因子-1对大鼠缺血再灌注损伤后急性炎症应答的影响

目的观察缺氧诱导因子-1对大鼠心肌缺血再灌注损伤后急性炎症应答的影响。方法健康清洁级大鼠24只,随机分为3组:二甲基乙二酰基甘氨酸(TMOG)组、对照组、假手术组,每组8只。TMOG组,在缺血与再灌注损伤模型建立前24h进行腹腔内注射20ug/gTMOG;对照组,在缺血与再灌注损伤模型建立前24h进行腹腔内注射生理盐水0.5mL;除假手术组,其余2组通过结扎冠状动脉左前降支60min,然后松开180min建立心肌缺血再灌注损伤动物模型;假手术组不结扎冠状动脉左前降支。3组大鼠均在实验终点采右心房血,分离血清,测定血清中的细胞间粘附分子-1(ICAM-1)、白细胞介素-8(IL-8)的表达水平;处死动物取出心脏,测定大鼠心肌组织的缺氧诱导因子-1的mRNA表达。结果TMOG组缺氧诱导因子-1的mRNA表达比对照组明显增多(P<0.05);TMOG组血清中的ICAM-1及IL-8的表达水平明显降低(P<0.05)。结论缺氧诱导因子-1能通过抑制ICAM、IL-8的合成,减少中性粒细胞的浸润,从而改善心肌缺血再灌注损伤,对心肌缺血再灌注损伤具有重要保护作用,为防治心肌缺血再灌注损伤提供了新的治疗思路。

Objective To observe the hypoxia-inducible factor -1 on myocardial ischemia-reperfusion injury in acute inflammatory response after impact. Methods 24 rats of clean grade were randomly divided into 3 groups： acyl ethylene dimethyl glycine （TMOG） group and the control group, sham-operated group,8 in each group.TMOG group, at ischemia and reperfusion injury model to set up before the 24h intraperitoneal injection 20ug/g TMOG; control group, at ischemia and reperfusion injury model set up to 24h before intraperitoneal injection of normal saline 0.5ml In addition to the sham-operated group,the other 2 groups through the left anterior descending coronary artery ligation and 60 wain, then release the 180 min set up myocardial ischemia reperfusion injury in animal models; sham-operated group did not left anterior descending coronary artery ligation.Three experimental rats at the end of all mining right atrial blood, separation of serum, the serum intercellular adhesion molecule -1 （ICAM-1）, Interleukin-8 （IL- 8） expression levels; killed animals removed heart, measured in rat myocardial tissue hypoxia inducible factor -1 of the mRNA. Results TMOG group of hypoxia-inducible factor-I of mRNA expression than the control group increased significantly（P〈0.05）; TMOG serum levels of ICAM-I and IL-8 expression level of significantly lower（P〈0.05）.Conclusion The hypoxia-inducible factor -1 through inhibiting ICAM, IL-8 synthesis, reduced neutrophil infiltration, thus improving myocardial ischemia-reperfusion injury of myocardial ischemia-reperfusion injury has important protective effects for the prevention and treatment myocardial ischemia-rePerfusion injury has provided a new treatment ideas.