【摘要】 目的评价异丙酚或氯胺酮对内毒素(LPS)性急性肺损伤大鼠肺小动脉骨形态构建蛋白-2(BMP-2)表达的影响。方法雌性Wistar大鼠60只,体重220-260g,6-7周龄。随机分为6组,每组10只。对照组(C组):1.5h内经股静脉输注生理盐水5ml;LPS组(L组):1h内输注生理盐水3 ml,然后30min内输注内毒素1mg／kg(溶于2ml生理盐水中);异丙酚20mg／kg+LPS组(P1组)、异丙酚50mg／kg+LPS组(P2组)、氯胺酮20mg／kg+LPS组(K1组)、氯胺酮50mg／kg+LPS组(K2组)1h内经股静脉分别输注不同剂量的药物,然后30min内输注LPS 1mg／kg(溶于2ml生理盐水中)。输注完毕后72h断头处死大鼠。RT-PCR法测定肺小动脉BMP-2 mRNA、Bax mRNA表达。免疫组织化学法、Western blot测定肺小动脉BMP-2、Bax、Bcl-2表达。显微成像分析系统测量肺小动脉中膜厚度。结果各组肺小动脉BMP-2、Bax、Bcl-2均有表达。与C组比较,其余组BMP-2、Bax蛋白水平和mRNA表达降低,Bcl-2水平升高(P<0.05或0．01)。与L组比较,异丙酚或氯胺酮使BMP-2、Bax蛋白水平及mRNA表达升高,Bcl-2水平降低(P<0.05)。各组肺小动脉中膜厚度较C组增加(P<0.05);异丙酚或氯胺酮减轻了肺小动脉中膜的增厚(P<0．05)。结论异丙酚或氯胺酮可以抑制大鼠LPS致急性肺损伤肺血管的重建,其机制可能与BMP-2、Bax基因表达上调,Bcl-2基因表达下调有关。更多还原

【Abstract】 Objective To investigate the effects of propofol or ketamine on BMP-2 expression in pudmonary arterioles in a rat model of acute lung injury ( ALI) induced by lipopolysaccharide (LPS) .Methods Sixty Wistar rats aged 6-7 weeks weighing 220-260 g were randomly divided into 6 groups with 10 animals in each group: groupⅠcontrol (C); groupⅡLPSs groupⅢpropofol 20 mg·kg-1 + LPS (P1); groupⅣpropofol 50 mg·kg-1 +LPS (P2); groupⅤketamine 20 mg·kg-1 + LPS (K1 ) and groupⅥketamine 50 mg·kg-1 + LPS (K2). ALI was induced by intravenous injection of LPS 1 mg·kg-1 in 2 ml of normal saline over 30 min. In the 4 pharmacological groups (groupⅢ,Ⅵ,Ⅴ,Ⅵ) different doses of propofol or ketamine was injected i. v. over 60 min followed by i.v. LPS. The animals were killed at 72 h after LPS. The lungs were immediately removed. The left lung was fixed with formalin, embedded in paraffin, sectioned at 5μm thick and stained with HE or by immunohistochemical method. The right lung was frozen in liquid nitrogen for determination of BMP-2, Bax, Bcl-2 expression in pulmonary arterioles by Western blot and RT-PCR. The thickeness of tunica media of pulmonary arterioles was measured by microphotograph analysis system.Results BMP-2, Bax and Bcl-2 expression was detected in pulmonary artery in all groups. LPS induced significant decrease in BMP-2 and Bax mRNA and protein and significant increase in Bcl-2 protein expression in groupⅡ-Ⅵ. Propofol and ketamine attenuated the changes in BMP-2 mRNA, Bax mRNA and protein expression induced by LPS. The thickness of tunica media of pulmonary arterioles was significantly increased by LPS in groupⅡ-Ⅵand propofol and ketamine significantly reduced the LPS-induced thickness. Conclusion Intravenous propofol or ketamine can inhibit pulmonary vascular remodeling by LPS, down-regulation of Bcl-2 gene expression and up-regulation of BMP-2 and Bax gene expression may be involved in the mechanism.更多还原