Application of gene therapy to acute lung injury

基因治疗在急性肺损伤中的应用

• 批准号: 08457399
• 负责人: KOTANI Naoki
• 金额: $ 4.93万
• 依托单位: HIROSAKI UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457399/
• 关键词: Alveolar macrophages; cytokine; gene expression; phagocytosis; microbicidal activity; 全身麻酔; 揮発性麻酔薬; インターロイキン-1; ハロセン; IFN; TNF; 肺障害; 麻酔

(1) human research : We harvested alveolar macrophages by bronchoalveolar lavage over time. The fraction of aggregated macrophages was determined. We then measured phagocytosis and microbicidal activity. We also exploited the power of the polymerase chain reaction (PCR) to amplify mRNAs of pro-inflammatory cytokines from AMs Phagocytic and microbicidal activity progressively decreased over time, with the decrease being greater during isoflurane than propofol anesthesia. Gene expression in IL-1, IL-8, IFNィイD2γィエD2, TNFィイD2αィエD2 increased over time. The increases in IL-8 and IFNィイD2γィエD2 were greater in isoflurane than in propofol anesthesia. We report progressive impairment of pulmonary immunologic function during anesthesia and surgery. Our data suggest that pulmonary defenses are modulated by the type of anesthesia, as well as the duration of anesthesia and surgery.(2) Animal study : Rats were mechanically ventilated with halothane, enflurane, isoflurane, or sevoflurane. After whole pulmonary lavage, we examined gene expression of the pro-inflammatory cytokines. Gene expression for IL-1, MIP-2, IFNィイD2γィエD2, and TNFィイD2αィエD2 all increased significantly compared with mechanical ventilation alone. These data indicate that inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response.

(1)人类研究：我们通过支气管肺泡灌洗随时间收获肺泡巨噬细胞。测定聚集的巨噬细胞的分数。然后，我们测量了吞噬作用和杀微生物活性。我们还利用聚合酶链反应（PCR）扩增AM中促炎细胞因子mRNA的能力。随着时间的推移，吞噬细胞和杀微生物活性逐渐下降，异氟烷麻醉期间的下降幅度大于丙泊酚麻醉期间。IL-1、IL-8、IFN γ D2、TNF α D2、IFN γ D2、TNF α D2的基因表达随时间增加。异氟醚麻醉时IL-8和IFN γ-γ-D2的升高幅度大于丙泊酚麻醉。我们报告了在麻醉和手术过程中肺免疫功能的进行性损害。我们的数据表明，肺防御是由麻醉的类型，以及麻醉和手术的持续时间调制。(2)动物研究：用氟烷、恩氟烷、异氟烷或七氟烷对大鼠进行机械通气。全肺灌洗后，我们检测了促炎细胞因子的基因表达。与单独机械通气相比，IL-1、MIP-2、IFN-γ D2和TNF-α D2的基因表达均显著增加。这些数据表明在机械通气下吸入挥发性麻醉剂诱导炎症反应。

项目成果

Kotani,N et al.: "Expression of genes for pro-inflamentry cytokine ・・・・"Anesthetics and Analysis. (掲載未定). (1999)

Kotani, N 等人：“促炎症细胞因子的基因表达……”麻醉与分析（出版待确定）。

Kotani, N., et al: "Expression of Genes for Pro-inflammatory Cytokines in Alveolar Macrophages during Propofol and Isoflurane Anesthesia"Anesthesia and Analgesia. (in press).

Kotani, N. 等人：“异丙酚和异氟烷麻醉期间肺泡巨噬细胞中促炎细胞因子的基因表达”麻醉和镇痛。

Kotani N,: "Intraoperative maduletim of alveolor macrophye fumetin" Anesthesiology. 98. 1125-1132 (1998)

Kotani N，：“术中使用肺泡巨藻福美丁”麻醉学。

Kotani,N.et al.: "Intraopiative modulation of locular macrophage funct ・・・・"Anesthesiology. 89. 1185-92 (1998)

Kotani, N. 等人：“局部巨噬细胞功能的术中调节……”麻醉学。 89. 1185-92 (1998)

Kotani N: "Gene expressin of cytrhines in at alaeslar maweophgus" Anerthesiology. 83. 1093-1093 (1997)

Kotani N：“翼状巨噬细胞中胞嘧啶的基因表达”麻醉学。