异丙酚对内毒素性急性肺损伤大鼠中性粒细胞NF—kB活化的影响

Effects of propofol on activation of NF-kB in polymorphonuclear neutrophils in rats with lipopolysaccharide-induced acute lung injury

目的探讨异丙酚对内毒素性急性肺损伤（ALI）大鼠中性粒细胞NF-kB活化的影响。方法健康清洁级SD大鼠60只，3月龄，体重250～350g，雌雄不拘，随机分为5组（n=12）：对照组（C组）、ALI组和不同剂量异丙酚组（P1组、P2组、P3组）。ALI组经股静脉注射LPS5mg／kg；P1组、P2组和P3组经股静脉注射LPS5mg／kg后立即分别静脉输注异丙酚5、10和15mg·kg-1·h-1，输注时间2h；C组经股静脉注射10ml生理盐水。异丙酚输注结束时，行肺组织病理学评分，采集颈动脉血样，测定中性粒细胞总NF-kB和活化的NF-kB的表达水平。结果与C组比较，ALI组、P1组和P2组肺组织病理学评分和中性粒细胞活化的NF-kB表达水平升高，P3组肺组织病理学评分升高（P〈0．05）；与ALI组比较，P2组和P3组肺组织病理学评分降低，P1组～P3组中性粒细胞活化的NF-kB表达水平降低（P〈0．05）；P1组～P3组肺组织病理学评分和中性粒细胞活化的NF-kB表达水平依次降低（P〈0．05）；各组中性粒细胞总NF-kB表达水平差异无统计学意义（P〉0．05）。结论异丙酚减轻大鼠内毒索性急性肺损伤的机制可能与抑制外周血中性粒细胞NF-kB的活化有关。

Objective To investigate the effects of propofol on activation of NF-kB in polymorphonuclear neutrophils （PMNs） in rats with LPS-induced acute lung injury （ALI） .Methods Sixty healthy SD rats of both sexes, aged 3 months, weighing 250-350 g, were randomly divided into 5 groups （ n = 12 each） ： control group （ group C）, ALI group and 3 different dose of propofol groups （group P1 , P2 , P3 ） - The animals were anesthetized with intraperitaneal 3% pentobarbital sodium 40 mg/kg. LPS 5 mg/kg was injected via femoral vein in group ALI. Propofol 5, 10 and 15 mg· kg- 1· h- 1 was infused intravenously over 2 h immediately after injection of LPS 5 mg/kg through femoral vein in group P1 , P2 and P3 respectivey. In group C normal saline 10 ml was injected via femoral vein instead. All rats were killed by exsanguination at the end of infusion of propofol. The right lung was removed for microscopic examination. The morphologic changes were scored 0-3 （0 = normal, 3 = severe morphologic changes） . Blood samples were collected from carotid artery for determination of the expression of total NF-kB and activated NF-kB in PMNs by Western blot. Results Compared with group C, morphologic change scores and activated NF-kB expression in PMNs were significantly increased in group ALI, P1 and P2, and morphologic change scores increased in group P3 - Morphologic change scores in group P1 and P2 and activated NF-kB expression in PMNs in group P1 , P2 and P3 were significantly decreased compared with those in group ALI. Morphologic change scores and activated NF-kB expression in PMNs were decreased gradually in group P1, P2 and P3 . There was no significant difference in total NF-kB expression in PMNs among all groups. Conclusion Propofol can attenuate ALI induced by LPS through inhibition of the activation of NF-kB in PMNs in rats.