不同时间给予猪肺表面活性物质对大鼠油酸型急性肺损伤疗效的影响

Influence of porcine pulmonary surfactant administered at different time on therapeutic effects in rats with oleic acid induced acute lung injury

目的探讨不同时间给予猪肺表面活性物质（PPS）混悬液对油酸致大鼠急性肺损伤（ALI）的治疗作用。方法将48只SD大鼠随机分为假手术组、模型组、0．5hPPS治疗组和2hPPS治疗组。假手术组仅行气管和颈动脉插管手术操作，其余各组大鼠静脉注入油酸诱发ALI；0．5hPPS治疗组和2hPPS治疗组分别于油酸注入后0．5h和2h经气道均滴入100mg／kg和150mg／kg两个剂量的PPS，实验过程中计数大鼠呼吸频率，测定动脉血气指标；于实验4h计算大鼠存活率后处死动物，观察肺组织病理学改变，并检测肺系数及支气管肺泡灌洗液（BALF）中总蛋白（TP）含量和血浆中肿瘤坏死因子-α（TNF-α）浓度。结果与模型组比较，0．5h给予PPS 100mg／kg和150mg／kg以及2h给予PPS 150mg／kg治疗都能显著降低大鼠的呼吸频率，提高动脉血氧分压（PaO2）及大鼠存活率，降低肺毛细血管通透性及肺出血、肺水肿发生率，降低血浆中TNF-α和BALF中TP含量（P均〈0．05）。而2h给予100mg／kgPPS的治疗作用不明显。结论早期气道内滴入≥100mg／kg的PPS，能明显改善油酸型ALI大鼠的呼吸功能、减轻肺损伤；晚期较大剂量的PPS（150mg／kg）才有治疗作用。

Objective To investigate the therapeutic effects of endotracheal instillating porcine pulmonary surfactant （PPS）given at different time on acute lung injury （ALI） induced by oleic acid （OA）. Methods Arterial blood gases and respiratory rate during the experiments, survival rate, lung index, total protein （TP） contents in bronchoalveolar lavage fluid （BALF）, tumor necrosis factor-α （TNF-α） level in plasma, light microscopy of the lung at 4 hours after the experiments Were examined in different groups of Sprague-Dawley （SD） rats： Group 1, sham group; Group 2, injected intravenously with OA 0.2 ml/kg; Group 3, injected intravenously with OA 0.2 ml/kg＋PPS 100 mg/kg 0.5 hour after OA; Group 4, injected intravenously with OA 0. 2 ml/kg＋PPS 150 mg/kg 0. 5 hour after OA; Group 5, injected intravenously with OA 0.2 ml/kg＋PPS 100 mg/kg 2 hours after OA; Group 6, injected intravenously with OA 0.2 ml/kg＋ PPS 150 mg/kg 2 hours after OA. Results Giving PPS not only improved the rats＇ （Group 3, Group 4 and Group 6） arterial blood gases and reduced respiratory rate, but also significantly raised their 4 hours-survival rate and decreased lung index, protein contents in BALF and TNF-α level in plasma, ameliorated pathohistological changes compared with Group 2 and Group 5 （all P 〈 0.05）. Conclusion PPS （100 mg/kg） administered at the early stage （0.5 hour after OA） provides obvious effects on respiratory efficiency and alleviates lung injury in rats with OA induced ALI, PPS （i50 mg/kg） at the late stage （2 hours after OA） has the same effects mentioned above, however PPS （100 mg/kg） given 2 hours after ALI has no therapeutic effects.