Effect of N-acetylcysteine on Acid Aspiration Followed by Ventilator-Induced Acute Lung Injury in a Rat Model

乙醯半胱胺酸在大白鼠模式下對酸吸入後伴隨呼吸器引發之急性肺損傷的作用

鄭鴻志(Hung-Tze Tay) ； 陳奇祥(Khee-Siang Chan) ； 陳欽明(Chin-Ming Chen)

《胸腔醫學》 32卷6期 (2017/12) Pp. 245-258

摘要

Introduction: To examine the pharmacological effects of N-acetylcysteine (NAC) in a 2-hit rat model of acid aspiration-induced inflammation followed by ventilator-induced lung injury (VILI). Methods: Rats received intra-tracheal instillation of hydrochloric acid as a first hit to induce systemic inflammation. For the second hit, they were randomized to receive mechanical ventilation (MV) using 1 of 2 strategies: a high tidal volume (TV) of 15 mL/kg and zero positive end-expiratory pressure (PEEP), or a protective strategy of a low TV of 6 mL/kg and a PEEP of 5 cm H2O. Rats in both groups were exposed to a fraction of inspired oxygen (FiO2) level of 40% during the 4-hour experimental period. Intravenous bolus of NAC (150 mg/ kg) or placebo was administered 30 minutes before the different MV strategies. The following variables were measured: blood gases, lung mechanics (static compliance and respiratory elastance), lung edema, extended lung destruction (lung injury scores and lung histology), neutrophil recruitment in the lung and cytokine/chemokine production. Results: Hemodynamics including blood pressure and heart rates did not differ between groups at baseline and during the study period. Compared to the placebo-treated rats, those administered NAC presented attenuated lung injury, as evidenced by improved oxygenation, preserved lung mechanics and diminished lung destruction and inflammation. Conclusion: Using the 2-hit rat model, NAC administration was found to improve the physiologic and biologic profiles of rats in this experimental VILI model.

關鍵字

acid aspiration ； inflammation ； N-acetylcysteine ； ventilator-induced lung injury

並列摘要

前言：檢視乙醯半胱胺酸在酸吸入造成之肺發炎後伴隨呼吸器引發之肺損傷的動物模式下之藥理作用。方法：大白鼠先接受氣管內注射鹽酸造成全身性發炎的一度傷害，之後再隨機接受兩種不同的呼吸器模式以造成二度傷害，包括15毫升/公斤之高潮氣容積合併零吐氣末正壓造成呼吸器引發肺損傷，或是6毫升/公斤之低潮氣容積合併5公分水柱吐氣末正壓之保護性呼吸器模式。實驗期間皆供應40%氧氣濃度及4個小時呼吸器使用。在實驗開始前30分鐘，先從靜脈投予乙醯半胱胺酸（150毫克/公斤）或是林格式液（對照組）。過程中監測以下參數：動脈血、肺靜態順應性、呼吸系統彈性、肺水腫、瀰漫性肺傷害嚴重度（肺傷害分數及肺組織病變）、肺泡內嗜中性白血球數及細胞激素/化學激素濃度。結果：實驗開始及過程中各組老鼠之血壓及心跳無顯著差異。跟對照組相比，注射乙醯半胱胺酸能夠減輕大白鼠之肺損傷，包括改善氧合、改善肺靜態順應性及呼吸系統彈性、減輕肺破壞、以及減少全身性發炎。結論：根據本實驗，乙醯半胱胺酸注射可以改善大白鼠肺損傷模式下之生理及生物參數。

並列關鍵字

胃酸吸入 ； 發炎 ； 乙醯半胱胺酸 ； 呼吸器引發肺損傷