异丙酚后处理对急性肺损伤大鼠肺组织Toll样受体4表达的影响  

The effects of postconditioning with propofol on Toll-like receptor 4 expression in the lung tissue of rat with acute lung injury

作　　者：李国福[1] 佟欣[1] 栾婷[1] 臧彬[1] 

机构地区：[1]110004辽宁沈阳,中国医科大学附属盛京医院重症医学科

出　　处：《中国危重病急救医学》2012年第10期620-623,共4页Chinese Critical Care Medicine

基　　金：辽宁省教育厅高等学校科研项目（2008825）

摘　　要：目的探讨异丙酚后处理对脂多糖（LPS）诱导急性肺损伤（ALI）大鼠肺组织中Toll样受体4（TLR4）表达的影响。方法将30只sD大鼠按随机数字表法分为对照组、Au组及异丙酚后处理组3组，每组10只。经股静脉泵入8mg／kgLPS30min诱导Au模型，对照组给予等量生理盐水。异丙酚后处理组于制模后股静脉推注20mg／kg异丙酚，再以40mg·kg-1·h-1微量泵匀速泵入维持1h。于给药结束后6h处死大鼠，取肺脏测定湿／干重（W／D）比值，计算肺通透性指数（LPI），用酶联免疫吸附试验（ELISA）测定支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF—α）水平，用逆转录-聚合酶链反应（RT—PCR）测定肺组织TLR4mRNA表达。结果与对照组比较，ALI组肺W／D比值、LPI、TLR4mRNA表达及BALF中TNF-α水平（ng／L）均明显升高[肺w／D比值：5．30±0．28比4．21±0．14，LPI（×100）：8．7±2．2比3．3±2．0，TLR4mRNA：2．451±0．028比0．998±0．021，TNF—α：643．46-4-62．31比120．43±12．65，均P〈0．05]；而异丙酚后处理组肺W／D比值、LPI、TLR4mRNA表达及BALF中TNF-α水平均较ALI组明显降低[肺W/D比值：4．68±0．19比5．30±0．28，LPI（×10^-3）：5．8±2．0比8．7±2．2，TLR4 mRNA：1．126±0．025比2．451±0．028，TNF—α：290．53±32．01比643．46±62．31，均P〈0．05]，但仍显著高于对照组（均P〈0．05）。结论异丙酚后处理能明显改善LPS诱导的ALI，其作用机制可能是通过下调TLR4mRNA表达，从而抑制“瀑布样”炎症反应。Objective To investigate the effect of postconditioning with propofol on Toll-like receptor 4 （TLR4） expression in the lung tissue in lipopolysaechafide （LPS）-induced acute lung injury （AH） rats. Methods Thirty Sprague-Dawley （SD） rats were randomly assigned to control group, ALl group, and propofol postconditioned group （ each n= 10 ）. The model of ALl was reproduced hy intravenous injection of LPS （ 8 mg/kg for 30 minutes ） into the rats, equivalent normal saline was injected into the rats of control group. The rats were postconditioned with propofol injected intravenously by 20 mg/kg bolus dose and then continuously by 40 mg·kg-1·h-1 with a constant speed for 1 hour. The rats were sacrificed 6 houm after drug injection. Lung wet/dry weight （W/D） ratio and lung permeability index （LPI） was taken. Tumor necrosis factor-α （ TNF-α ） level in bronchoalveolar lavage fluid （ BALF ） was detected using enzyme linked immunosorbent assay （ELISA） method and TLR4 mRNA expression in lung tissue was assessed by reverse transeription-polymerase chain reaction （RT-PCR）. Results The lung W/D ratio, LPI, TLR4 mRNA and TNF-α （ng/L） in BALF were all increased in ALl group compared with control group [lung W/D ratio： 5.30 ± 0.28 vs. 4.21± 0.14, LH （ × 10^-3） ： 8.7 ± 2.2 vs. 3.3 ± 2.0, TLR4 mRNA： 2.451 ± 0.028 vs. 0.998 ± 0.021, TNF-α： 643.46 ± 62.31 vs. 120.43 ± 12.65, all P〈0.05 ]. The above indexes were significantly reduced in the propofol group than those in the ALI group [lung W/D ratio： 4.68 ± 0.19 vs. 5.30 ± 0.28, LPI （ × 10-3） ： 5.8 ± 2.0 vs. 8.7 ± 2.2, TLR4 mRNA： 1.126 ± 0.025 vs. 2.451 ± 0.028, TNF-α： 290.53 ± 32.01 vs. 643.46 ± 62.31, all P〈0.05 ], but still higher than those in control group （ all P〈0.05 ）. Conclusion Postconditioning with propofol may alleviate ALl via reducing TLR4 mRNA expression, and inhibit the waterfall-like inflammatory reaction.

关 键 词：异丙酚 后处理 急性肺损伤 TOLL样受体 

分 类 号：R563.8[医药卫生—呼吸系统]