摘要
目的:建立呼吸机相关性肺损伤(ventilator associated lung injury,VALI)大鼠模型,了解磷酸酰肌醇-3激酶γ(phosphatidylinositol 3-hydroxy kinase gamma,PI3Kγ)小分子抑制剂AS605240对其的影响,探讨可能的作用机制。方法:将30只SD大鼠随机均分为3组:对照组、VALI模型组和AS605240处理组。对照组不作机械通气处理;VALI模型组行大潮气量(40 ml/kg)机械通气;AS605240处理组,机械通气前10 min静脉预注AS605240 20 mg/kg。大鼠机械通气4 h后放血处死,计算肺湿干重(W/D)比值。收集肺泡灌洗液(broncho alveolar lavage fluid,BALF),测定其总蛋白含量并行白细胞(WBC)计数。采用酶联免疫吸附法测定血清肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-6、IL-8及IL-10的细胞因子浓度,比色法测定血清和BALF中超氧化物歧化酶(superoxide dismu-tase,SOD)活性及丙二醛(methane dicarboxylic aldehyde,MDA)浓度。结果:(1)与对照组相比,AS605240处理组与VALI模型组其W/D、WBC计数、总蛋白含量均升高(均P<0.05);AS605240处理组与VALI模型组相比,AS605240组W/D、WBC计数、TP含量均降低(均P<0.05)。(2)与对照组相比,AS605240处理组与VALI模型组大鼠BALF和血清中TNF-α、IL-6、IL-8水平和MDA活性均明显升高、而IL-10和SOD浓度则明显降低(均P<0.05)。与VALI模型组相比,AS605240组BALF及血清中TNF-α、IL-6、IL-8和MDA活性降低,IL-10和SOD浓度增高(均P<0.05)。结论:AS605240能够有效防治VALI,其机制可能与抑制各种炎性因子、抑制肺部微循环通透性的增加及减少内脂质过氧化等有关。
Objective：To investigate the effect of PI3Kγ inhibitor AS605240 pretreat-ment in a rat model of ventilator associated lung injury（VALI）and its possible mechanisms. Methods：Thirty male SD rats were randomly divided into 3 groups： control group,VALI model group,and AS605240 treatment group. No mechanical ventilation was conducted in control group;mechanical ventilation with40 ml/kg tidal volume was applied in VALI model group;intravenous injection of 20 mg/kg AS605240 was employed in AS605240 treatment group at 10 min before the mechanical ventilation. The animals were sacrificed by exsanguinations at the end of 4 h mechanical ventilation. The lungs were removed,and the wet to dry weight ratio（W/D）was measured. Broncho alveolar lavage fluid（BLAF）was obtained for determination of total protein（TP）contents and WBC counts. The levels of tumor necrosis factor-α（TNF-α）,interleukin（IL）-6,IL-8 and IL-10 in the serum and BALF were detected by enzyme linked immunosorbent assay. The levels of SOD and MDA were detected by colorimetric method. Results：W/D,WBC counts,TP content were increased in AS605240 treatment group and VALI model group compared with those of control group（all P0.05）. W/D,WBC counts,TP content were lower in AS605240 treatment group than in VALI model group（all P0.05）. Levels of TNF-α,IL-6,IL-8 and MDA in serum and BALF were significantly increased in VALI model group and AS605240 treatment group than in control group;but the levels of IL-10 and SOD were significantly decreased（all P 0.05）. Compared with those of VALI model group,the levels of TNF-α,IL-6,IL-8 and MDA in serum and BALF were decreased,but IL-10 and SOD were increased in AS605240 treatment group（all P0.05）. Conclusion：Pretreatment with AS605240 can effectively treat VALI in rats through suppressing the generation of oxygen free radicals and the release of inflammatory cytokines. Its mechanism may be inhibition of variety of inflammatory factors,inhibition of pulmonary microcirculation permeability and decrease in lipid peroxideation,etc.
出处
《重庆医科大学学报》
CAS
CSCD
北大核心
2016年第4期332-335,共4页
Journal of Chongqing Medical University
基金
江西省科技厅资助项目(编号:20111BBG700202)
江西省自然基金资助项目(编号:2011ZBAB204023)
关键词
磷酸酰肌醇-3激酶γ
呼吸机相关性肺损伤
炎性细胞因子
氧自由基
phosphatidylinositol 3-hydroxy kinase gamma
ventilator associated lung injury
inflammatory cytokines
oxygen free radicals
作者简介
王红鸾，Email：13517003319@1163．com，研究方向：肺部感染，机械通气。
通信作者：李秋根。Email：hlwangxie@126．com。
