异丙酚对肢体缺血/再灌注大鼠肺损伤的影响

Effects of propofol on lung injury following ischemia-reperfusion of hind limbs in rats

目的观察异丙酚对肢体缺血/再灌注大鼠肺损伤的影响。方法健康Wistar大鼠36只,体重300-350g,随机分为3组:假手术组(Sham组,n=12),只进行手术操作不做其他处理;肢体缺血/再灌注组(I/R组,n=12),双后肢缺血4h、再灌注6h;异丙酚组(P组,n=12)于开放前10min静脉注射异丙酚5mg·kg-1随后以10mg·kg-1·h-1的速率输注,I/R、Sham组输注等量生理盐水。实验结束,颈动脉放血处死大鼠,测定肺组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性及肺组织含水率,光镜和电镜下观察肺组织形态学改变及肺组织诱导型一氧化氮合酶(iNOS)、细胞间黏附分子-1(ICAM-1)的表达。结果肺含水率:I/R、P组均较Sham组增加,但P组低于I/R组(P<0.05或0.01);肺组织MDA含量:I/R组较Sham组升高,P组低于I/R组(P<0.01),且与Sham组相比差异无统计学意义(P>0.05);肺组织SOD活性:I/R、P组均较Sham组降低,但P组高于I/R组(P<0.01或0.05)。光镜观察,I/R组肺间隔增厚,间质中有大量中性粒细胞浸润,局部肺出现不张、肺泡水肿;电镜观察,I/R组部分肺泡上皮细胞缺损,Ⅰ型上皮细胞肿胀,Ⅱ型上皮细胞微绒毛稀疏、板层小体排空,P组肺组织病变明显改善。P组肺组织iNOS、ICAM-1表达较I/R组明显减少。结论异丙酚对肢体缺血,再灌注大鼠肺损伤具有一定程度的保护作用,其机制可能与减轻肢体缺血/再灌注后肺组织的氧化损伤及下调损伤肺组织iNOS、ICAM-1表达有关。

Objective To investigate the protective effects of propofol against lung injury following ischemia-reperfusion of hind limbs. Methods Thirty-six Wistar rats weighing 300-350 g were anesthetized with mtraperitoneal 3% pentobarbital 40 mg·kg-1. Bilateral femoral artery and vein were exposed for occlusion of the circulation of the hind limbs. Right internal jugular vein was cannulated for drug administration. The animals were randomly assigned into 3 groups ( n = 12 in each group) : (1) sham-operated group in which bilateral femoral artery and vein were exposed but not occluded; (2) I/R group in which the bilateral femoral artery and vein were occluded for 4h with the atraumatic microclips and the released for 6h reperfusion , and (3) I/R + propofol group received a bolus of 5 mg·kg-1 propofol 10 min before reperfusion followed by propofol infusion at 10 mg·kg-1·h-1. In group 1 and 2 the animals received same amount of normal saline instead of propofol. At the end of 6h reperfusion the animals were sacrificed by bloodletting. The lungs were immediately removed for determination of MDA content, SOD activity, the lung water, iNOS and ICAM-1 expression and microscopic examination. Results I/R significantly increased lung water and MDA content, and expression of iNOS and ICAM-1 and decreased SOD activity, while propofol significantly attenuated these changes induced by I/R of hind limbs. Light microscopic findings in I/R group included alveolar edema, localized pulmonary atelectasis and hemorrhage and large amount of polymorphonuclear infiltration. Electron microscopic examination showed a series of ultrastructural changes such as diffuse irregular thickening of basement membrene, alveolar type Ⅰ cell swelling, alveolar type Ⅱ cell injury associated with emptying of lamella bodies. These changes were significantly less prominent in the rats which received propofol. Conclusion Propofol has protective effects on the lungs against injury induced by I/R of the hind limbs.