异丙酚或氯胺酮对内毒素性急性肺损伤大鼠肺小动脉BMP-2表达的影响  

Effects of propofol and ketamine on BMP-2 expression in pulmonary arterioles in a rat model of LPS-induced acute lung injury

作　　者：裴凌[1] 单世民[1] 王俊科[1] 

机构地区：[1]中国医科大学第一附属医院麻醉科,沈阳市110001

出　　处：《中华麻醉学杂志》2006年第12期1093-1097,共5页Chinese Journal of Anesthesiology

基　　金：辽宁省教育厅基金资助项目(202013168)

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。Objective To investigate the effects of propofol or ketamine on BMP-2 expression in pulmonary 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 ： group Ⅰ control （C） ; group Ⅱ LPS ; group Ⅲ propofol 20 mg·kg^-1 ＋ LPS （ P1 ） ; group Ⅳ propofol 50 mg·kg^-1 ＋ LPS （ P2 ） ; group Ⅴ ketamine 20 mg·kg^-1 ＋ LPS （ K1 ） and group Ⅵ ketamine 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 （group Ⅲ , 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 5 μm thick and stained with HE or by 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 group Ⅱ -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 group Ⅱ -Ⅵ and propofol and ketamine significantly reduced the LPS-induced thickness. Conclusion Intravenous propofol or ketamine can inhibit pulmonary vascular remodelingby LPS, down-regulation of Bcl-2 gene expression and up-regulation of BMP-2 and Bax gene expression may be involved in the mechanism.

关 键 词：二异丙酚 氯胺酮 内毒素血症 呼吸窘迫综合征 成人 骨形态发生蛋白质类 

分 类 号：R96[医药卫生—药理学]