异丙酚预先给药对心肌缺血再灌注损伤大鼠炎性反应的影响

Effects of propofol on the inflammatory response to myocardial ischemia-reperfusion injury in rats

目的探讨异丙酚预先给药对心肌缺血再灌注损伤大鼠炎性反应的影响。方法健康雄性SD大鼠48只,随机分为4组(n=12):假手术组(S组)、缺血再灌注组(I／R组)、低剂量异丙酚组(L组)、高剂量异丙酚组(H组)。结扎左冠状动脉前降支(LAD)30 min、再灌注120 min,建立大鼠心肌缺血再灌注损伤模型。分别于再灌注30 min(T1)、120 min(T2)时采集股动脉血1ml,ELISA法测定血浆肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)的浓度,再灌注120 min时TIC法测心肌梗死面积,电镜下观察心肌细胞超微结构。结果与S组比较,I／R组、L组、H组在T1、T2时TNF-α、IL-10浓度升高(P<0．05);与I／R组比较,L组、H组在T1、T2时TNF-α浓度降低(P<0．05),IL-10浓度升高(P< 0．05),心肌梗死面积减小(P<0．05);L组比较,H组T1、T2时,TNF-α浓度降低,IL-10浓度升高,心肌梗死面积减小(P<0．05)。电镜下观察I／R组心肌细胞超微结构改变严重,L组、H组心肌细胞超微结构改变程度较I／R组轻。结论异丙酚预先给药通过抑制再灌注诱发的炎性反应减轻了大鼠心肌缺血再灌注损伤。

Objective To investigate the effects of propofol pretreatment on the inflammatory response induced by myocardial ischemia-reperfusion （I/R） .Methods Forty-eight healthy male SD rats weighing 200-250 g were randomly divided into 4 groups （ n = 12 each） ; group S sham operation; group I/R; group L low-dose propofol ＋ I/R and group H high-dose propofol ＋ I/R. In group I/R, L and H myocardial I/R was produced by occlusion of left anterior descending artery （LAD） for 30 min followed by 120 min repeffusion. In group L and H propofol 5 and 10 mg·kg^-1 was given IV 10 min before occlusion of LAD, followed by propofol infusion at 5 or 10 mg·kg^-1·h^-1 until the animals were killed at 120 min of reperfusion. Blood samples were taken at 30 min （T1） and 120 min （T2） of reperfusion for determination of plasma TNF-α and IL-10 by ELISA. The size of myocardial infarct was determined by TIC and the myocardial histopathologieal changes were determined by electron microscopy. Results The plasma TNF-α and IL-10 levels at T1 and T2 were slgnifieant higher in group I/R, L and H than in group S （P 〈 0.05）. The plasma TNF-α level was significantly lower while the plasma IL-10 level was significantly higher in group L and H than in group I/R. The size of myocardial infarct was significantly smaller in group L and H than in group I/R. The myocardial histopathologieal changes were mild in group L as compared with group I/R, while in group H the microscopic structure of myooardium was basically normal. The protective effects of propofol was dose-dependent. Conclusion Propofol pretreatment can protect the myocardium against isehemiarepcrfusion injury through inhibition of I/R induced inflammatory response.