Isoproterenol Ameliorates hyperoxia-induced Lung Dysfunctions and Injuries

Isoproterenol對高濃度氧引起的肺功能障礙與損傷之影響

程素玲(Su-Ling Chen) ； 毛蕙心(Hui-Hsing Mao) ； 王志偉(Chi-Wei Wang) ； 黃秋峰(Chiu-Feng Huang) ； 周士軒(Shih-Hsuan Chou) ； 郭敏玲(Ming-Ling Kuo) ； 蔡熒煌(Ying-Huang Tasi) ； 陳培然(Pei-Jan Chen) ； 樓迎統(Ying-Tung Lau)

《呼吸治療》 8卷1期 (2009/01) Pp. 15-29

https://doi.org/10.6269/JRT.2009.8.1.02

摘要

研究目的：過去實驗認爲高濃度氧（高氧）引起急性肺損傷，是來自於氧化壓力與發炎反應，所導致的內皮及上皮細胞死亡，但是其中沒有直接證據指出，氧化壓力是高氧引起呼吸功能障礙與損傷之原因，它們之間的關係並不是很清楚，因此本研究想瞭解高氧引起的呼吸功能障礙與肺損傷和氧化壓力之相關性，以及維生素C和isoproterenol 在其中所具有的影響。 研究方法：將8-10週雄性Sprague-Dawley大白鼠隨機分成兩組，在一大氣壓下分別給予空氣(Air)和大於95%的氧(O2)，在8、24、48小時測量呼吸功能（通氣及動脈血氣體分析）與肺氧化狀態（超氧陰離子的產生、抗氧化酵素活性及脂質過氧化情形）。另外分別皮下注射抗氧化劑（維生素C）和短效乙二型腎上腺接受器致效劑(isoproterenol)，在高氧48小時時，觀察其對呼吸功能與氧化狀態變化之影響。 研究結果：高氧24小時肺組織超氧陰離子(superoxide anion, O2(上标 •-)的產生、抗氧化酵素穀胱甘過氧化酶(glutathione peroxidase, GPx)的活性及脂質過氧化產物(malondialdehyde, MDA)皆顯著增加，導致明顯的氧化傷害。呼吸功能（通氣及動脈血氧）除了呼吸道阻力（高的Pench值）增加外，其它沒有明顯的改變。高氧48小時氧化傷害沒有持續出現，但是所有呼吸功能皆明顯受損，同時發生肺組織水腫之形態病理變化。另外給予維生素C、isoproterenol或生理食鹽水，在高氧48小時發現，isoproterenol可以有效改善高氧引起的呼吸功能障礙、氣體交換損傷及肺組織水腫情形，然而維生素C沒有顯著作用。 結論：從高氧引起的氧化壓力和呼吸功能障礙與肺損傷之時間上的關係，以及isoproterenol可以有效改善的情況，這些結果指出除了氧化壓力外，腎上腺接受器傳遞的機轉和氧化壓力，在高氧引起的呼吸功能障礙與肺損傷中扮演重要的角色。

關鍵字

高濃度氧 ； 氧化壓力 ； 呼吸到阻力 ； 肺損傷 ； 乙型腎上腺接受器致效劑

並列摘要

Background and objective: Hyperoxic acute lung injury is characterized by oxidative stress and inflammatory response, leading to endothelial and epithelial cell death. The temporal relationship between oxidative stress and respiratory dysfunction/injuries needs to be clarified.
Methods: The progression of lung dysfunction (ventilation and blood gas) as well as injuries (oxidative and inflammatory) following hyperoxia were determined and the effects of antioxidant (vitamin C) and adrenoceptor agonist (isoproterenol) on the hyperoxia (48h)-challenged male Sprague-Dawley rats (8-10 wk) were tested.
Results: Normobaric hyperoxia caused significant oxidative damages as determined by NADPH-dependent superoxide anion (O2(superscript •-)) production, antioxidant enzyme glutathione peroxidase (GPx), and malondialdehyde (MDA) at 24h post-hyperoxia. Respiratory functions (ventilation and blood oxygen) did not alter significantly except that airway resistance (higher Penh value) increased at this time point. At 48h post-hyperoxia, oxidative damages were no longer apparent, however, all respiratory functions were impaired significantly. Morphological changes including tissue swelling was also observed. In a separate experiment, pretreatment of vitamin C, isoproterenol, or saline followed by hyperoxia was performed. We found that isoproterenol, but not vitamin C was effective in ameliorating the hyperoxia-induced respiratory dysfunction, impairment of gas exchange, as well as tissue swelling.
Conclusions: We have tested a model for defining time course of hyperoxia-induced respiratory dysfunction, oxidative stress, and lung injuries. Isoproterenol was found effective in improving these conditions and thus indicate that adrenoceptor-mediated events, in addition to oxidative stress, may play a significant role in hyperoxia-induced respiratory dysfunction and injuries.

並列關鍵字

hyperoxia ； oxidative stress ； airway resistance ； lung injuries ； β agonist