Intervention effect of PI3Kγ inhibitor AS605240 on ventilator associated lung injury in rats

Wang Hongluan; Wang Jun; Guo Shaomei; Cai Jinglian; Fu Qiang; Yu Jie; Li Qiugen

doi:10.13406/j.cnki.cyxb.000891

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Intervention effect of PI3Kγ inhibitor AS605240 on ventilator associated lung injury in rats

更新时间：2024-01-17

- Intervention effect of PI3Kγ inhibitor AS605240 on ventilator associated lung injury in rats
- Journal of Chongqing Medical University Vol. 41, Issue 4, Pages: 332-335(2016)
- 作者机构：
  
  1. 南昌大学研究生院
  2. 江西省人民医院二部呼吸内科
- 作者简介：
- 基金信息：
- DOI：10.13406/j.cnki.cyxb.000891
  CLC： R563.9
- Published：2016，
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[1]王红鸾,汪俊,郭韶梅,蔡金莲,付强,喻杰,李秋根.磷酸酰肌醇-3激酶γ抑制剂AS605240对治疗呼吸机相关性肺损伤大鼠的影响[J].重庆医科大学学报,2016,41(04):332-335.

Wang Hongluan, Wang Jun, Guo Shaomei, et al. Intervention effect of PI3Kγ inhibitor AS605240 on ventilator associated lung injury in rats. [J]. Journal of Chongqing Medical University 41(4):332-335(2016)
[1]王红鸾,汪俊,郭韶梅,蔡金莲,付强,喻杰,李秋根.磷酸酰肌醇-3激酶γ抑制剂AS605240对治疗呼吸机相关性肺损伤大鼠的影响[J].重庆医科大学学报,2016,41(04):332-335. DOI： 10.13406/j.cnki.cyxb.000891.

Wang Hongluan, Wang Jun, Guo Shaomei, et al. Intervention effect of PI3Kγ inhibitor AS605240 on ventilator associated lung injury in rats. [J]. Journal of Chongqing Medical University 41(4):332-335(2016) DOI： 10.13406/j.cnki.cyxb.000891.

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。

Abstract

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 P<0.05). W/D

WBC counts

TP content were lower in AS605240 treatment group than in VALI model group(all P<0.05). 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 P<0.05). 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.

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

Keywords

phosphatidylinositol 3-hydroxy kinase gammaventilator associated lung injuryinflammatory cytokinesoxygen free radicals

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