Roles of nitric oxide and neuropeptides in the development of lung injuries induced by chemical irritants.

一氧化氮和神经肽在化学刺激物引起的肺损伤发展中的作用。

• 批准号: 08670401
• 负责人: OMAE Kazuyuki
• 金额: $ 1.41万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670401/
• 关键词: ozone; nittric oxide; neuropeptide; substance P; neurokinin A; airway responsiveness; サブスタンスP; ニューロキニンA

Inhalation studies were performed to examine roles of neuropeptides and nitric oxide in airway responses to ozone in rats or mice.1.Role of neuropeptidesThe purpose of this study was to determine whether tachykinins mediate the protective effects of C-fibers against ozone (O_3) exposure. Male Sprague-Dawley rats were exposed to 1ppm O_3 or air for three hours. Two hours later airway responsiveness to inhaled methacholine was measured and a bronchoalveolar lavage (BAL) was performed. Rats were treated with the selective NK_1 and NK_2 receptor antagonist, either throughout the O_3 exposure and methacholine challenge or just before the methacholine challenge. The effect of neonatal capsaicin pretreatment, which ablates C-fibers, on O_3-induced changes in BAL cells and protein was also examined. Pretreatment of rats with the antagonists during O_3 exposure significantly augmented influx of neutrophils into the lung and airways and shedding of epithelial cells. Pretreatment of rats with the … More antagonists after the O_3 exposure had no effect on BAL cell recovery. Neither treatment had any effect on baseline pulmonary mechanics or airway responsiveness. Neonatal capsaicin pretreatment. which ablates C-fibers, also resulted in increased BAL neutrophils and protein after O_3 compared to vehicle treated rats. These results suggest that tachykinins mediate protective effects of C fibers against O_3-induced lung injury, but are not involved in attenuating the development of airway hyperresponsiveness.2.Role of nitric oxideThe purpose of this study was to examine whether nitric oxide mediate airway responses to O_3. Male ICR mice with/without N-Nitro-Arginine (NOARG,100mg/kg) were exposed to 1ppm O_3 or air for four hours. Twenty-four hours later a bronchoalveolar lavage (BAL) was performed. Number of neutrophils in BAL fluid was decreased in the O_3/NOARG group, which indicated nitric oxide might relate to development of O_3 induced-airway inflammation. We further evaluated the role of nitric oxide in O_3-induced airway hyperresponsiveness, but no clear relationship was observed. Less

本研究采用大鼠和小鼠吸入臭氧实验，观察了神经肽和一氧化氮在臭氧暴露气道反应中的作用。1.神经肽的作用本研究的目的是探讨速激肽是否介导C纤维对臭氧（O_3）暴露的保护作用。雄性Sprague-Dawley大鼠暴露于1 ppm O_3或空气中3小时。两小时后测定气道对吸入乙酰甲胆碱的反应性，并进行支气管肺泡灌洗（BAL）。在O_3暴露和乙酰甲胆碱激发的整个过程中或在乙酰甲胆碱激发之前，用选择性NK_1和NK_2受体拮抗剂处理大鼠。新生儿辣椒素预处理，消融C-纤维，对O_3诱导的BAL细胞和蛋白质的变化的影响也进行了研究。在O_3暴露期间用拮抗剂预处理大鼠，可显著增加中性粒细胞向肺和气道的内流以及上皮细胞的脱落。大鼠预处理 ...更多信息 O_3暴露后，拮抗剂对BAL细胞恢复无影响。两种治疗对基线肺力学或气道反应性均无任何影响。新生儿辣椒素预处理。与溶剂处理的大鼠相比，其消融C-纤维也导致O_3后BAL中性粒细胞和蛋白质的增加。提示速激肽介导了C纤维对O_3所致肺损伤的保护作用，但不参与减轻气道高反应性的形成。2.一氧化氮的作用本研究旨在探讨一氧化氮是否介导了O_3所致的气道反应。将含/不含N-硝基-精氨酸（NOARG，100 mg/kg）的雄性ICR小鼠暴露于1 ppm O_3或空气中4小时。24小时后进行支气管肺泡灌洗（BAL）。O_3/NOARG组BALF中中性粒细胞数减少，提示NO可能与O_3诱导的气道炎症有关。我们进一步评估了一氧化氮在O_3诱导的气道高反应性中的作用，但没有观察到明确的关系。少

项目成果

武林 亨 他: "呼吸器刺激ガズ吸入による肺傷害の発生におけるneuropeptides、一酸化窒素の役割." 産業衛生学雑誌. 38. S513 (1996)

Toru Takebayashi 等人：“神经肽和一氧化氮在呼吸气体吸入引起的肺损伤中的作用。工业卫生杂志”38。S513（1996）。

Takebayashi T., Satoh, T., Kagawa, J., Omae, K., Sakurai, H.: "Roles of neuropeptides and nitric oxide in airway injuries induced by chemical irritants." Sangyo-Eiseigaku-Zassi. 38. S513 (1996)

Takebayashi T.、Satoh, T.、Kakawa, J.、Omae, K.、Sakurai, H.：“神经肽和一氧化氮在化学刺激物引起的气道损伤中的作用。”

Takabayashi T., Skornik WA,Shore SA.: "Role of tachykinins in airway responses to ozone in rats." Am J Respir Crit Care Med. 153. A161 (1996)

Takabayashi T.，Skornik WA，Shore SA.：“速激肽在大鼠气道对臭氧反应中的作用。”

Takebayashi T. et al.: "Role of techykinins in airway responses to ozone in rats" Am J Respir Crit Care Med.153. A161 (1996)

Takebayashi T. 等人：“Techykinins 在大鼠气道对臭氧反应中的作用”Am J Respir Crit Care Med.153。

Takebayashi T.,Skornik W.A.,Shore S.A.: "Role of tachykinins in airway responses to ozone in rats." Am J Respir Crit Care Med. 153. A161. (1996)

Takebayashi T.、Skornik W.A.、Shore S.A.：“速激肽在大鼠气道对臭氧反应中的作用。”