摘要
目的观察异丙酚对大鼠油酸性急性肺损伤(ALI)的保护作用及其机制。方法 40只成年雄性 SD 大鼠,体重：250～290g,随机分成5组：正常对照组(Ⅰ组)、ALI 组(Ⅱ组)、4mg·kg^(-1)·h^(-1) 异丙酚治疗组(Ⅲ组)、8mg·kg^(-1)·h^(-1)异丙酚治疗组(Ⅳ组)、16mg·kg^(-1)·h^(-1)异丙酚治疗组(Ⅴ组)；Ⅱ～Ⅴ组静脉注射油酸250μl·kg^(-1)制备大鼠 ALI 模型,然后Ⅲ～Ⅴ组持续静脉输注异丙酚4h 时处死大鼠。测定肺组织 MDA 含量及 MPO、SOD 活性；透射电镜观察肺组织超微结构变化；免疫组化及流式细胞术测定肺组织白介素(IL)-18、IL-10水平；电泳迁移率变动分析技术测定肺组织 NF-(?)B 的表达。结果电镜显示Ⅱ组肺泡Ⅱ型上皮细胞线粒体、粗面内质网及嗜锇性板层小体损伤；Ⅲ～Ⅴ组肺泡Ⅱ型上皮细胞细胞器损伤均有不同程度改善,尤以Ⅳ组效果明显。与Ⅰ组比较,Ⅱ组肺组织 MDA、IL-10、 IL-18、NF-(?)B 水平升高,MPO、SOD 活性降低(P＜0.05)；静脉输注异丙酚使 ALI 大鼠肺组织 MPO、SOD 活性升高,MDA、IL-18、NF-(?)B 水平降低,IL-10水平升高(P＜0.05)。结论 4～16mg·kg^(-1)·h^(-1)异丙酚均可抑制油酸性 ALI 时的氧化应激反应,阻断 NF-(?)B 的活化,减轻肺部炎性反应,对油酸性 ALI 起到一定的保护作用,8mg·kg^(-1)·h^(-1)剂量效果较好。
Objective To investigate the protective effects of pmpofol against acute lung injury （ALI） induced by oleic acid. Methods Forty adult male SD rats weighing 250-290 g were anesthetized with intrapefitoneal （i.p.） 20% urethrane 6 ml· kg^-1 and tracheostomized. Left common carotid artery and fight internal jugular vein were cannulated for BP monitoring and fluid and drug administration. The animals were randomly divided into 5 groups （ n = 8 each） ： Ⅰ control group; Ⅱ ALl group in which ALI was induced by oleic acid 250 mg· kg^-1 i.v. ;Ⅲ , Ⅳ and V ALI ＋ propofol group in which propofol was continuously infused i.v. at 4, 8 and 16 mg· kg^-1· h^- 1 for 4 h immediately after i.v. oleic acid. The animals were killed at 4 h after oleic acid adnfinistration. The lungs were immediately removed for （1） examination of ultrastrueture of the lung with transmission electron microscope and （2） determination of SOD and MPO activity, content of MDA, level of IL-10 and IL-18 and expression of NF-kB in lung tissue. Results In group Ⅱ intravenous oleic acid produced damage to mitochondria, rough endoplasmic reticulum and osmiophilic multi-lamellar body in type Ⅱ alveolar epithelial cells. Propofol infusion in group Ⅲ, Ⅳ and Ⅴ attenuated the damage to different degrees. In group Ⅱ i.v. oleic acid produced significant decrease in MPO and SOD activity and significant increase in MDA content, IL-10, IL-18 and NF-kB expression in lung tissue. Intravenous propofol infusion attenuated the decrease in MPO and SOD activity, increase in IL-18 expression and MDA content and NF-kB expression in lung tissue produced by i.v. oleic acid, but increased IL-10 expression in lung tissue further. The best protective effect was seen in group Ⅳ. Conclusion Propofol i.v. infusion at 4-16 mg· kg^-1· h^-1 can inhibit the oxidative response, and inflammatory response and down-regulate NF-kB expression in lung tissue. Propofol infusion at 8 mg· kg^-1· h^-1 provides best protective effects.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2006年第1期57-60,共4页
Chinese Journal of Anesthesiology
