低剂量全氟异丁烯致大鼠急性肺损伤及清开灵早期治疗长期效果观察

摘要

OBJECTIVE To clarify the long-term toxicity to the respiratory system in a rat model of acute lung injury (ALI) induced by a single low-dose of perfluoroisobutylene(PFIB) inhalation expo⁃sure,and observe the possible beneficial effect of early intervention via Qingkailing(QKL) injection. METHODS Totally 224 male Wistar rats were randomly divided into 4 groups:normal control group in which air exposure was followed by a saline 10 mL · kg-1(ip),QKL control group in which QKL 10 mL · kg-1 was ip given after air exposure,PFIB exposure group in which rats were exposed to PFIB 280 mg·m-3 for 5 min only,and QKL treatment group in which QKL 10 mL·kg-1 was given ip at 1 h after PFIB exposure. Lung functions of rats were measured at 24 h,3,6,12,24,36 and 48 weeks after exposure. The arterial blood gas,lung coefficient,protein content in bronchoalveolar lavage fluid(BALF),hydroxy⁃proline(HYP) content in lung tissue and plasma,and other indicators were detected or analyzed. RESULTS Within 24 h after PFIB exposure,the lung coefficient and protein content in BALF were increased significantly(P<0.01),whereas the PaO2(P<0.01) and SaO2(P<0.05) indices in arterial blood decreased significantly in PFIB group compared with normal control. The inhalation time , exhalation time,tidal volume(TV),expired volume(EV)and relaxed time were reduced significantly (P<0.01). However,all the above indicators returned to normal in 3 weeks,but TV,EV and peak expiratory flow were significantly lower than in normal group at 48 weeks(P<0.05). HYP contents in lung tissues,compared with normal control(P<0.05),were reduced significantly within 24 h after PFIB exposure,increased significantly in 6 weeks(P<0.05),then returned to normal in 12 weeks. HYP contents in plasma increased significantly compared with normal control(P<0.05) within 24 h after PFIB exposure but returned to normal in 3 weeks. The protein contents in BALF of QKL treatment group were significantly lower than those in PFIB group(P<0.01) within 24 h after PFIB exposure. From 24 h to 24 weeks after PFIB exposure,changes of pulmonary functions were similar to those in PFIB group. At 48 weeks,TV and EV in QKL treatment group were more significantly increased than those in PFIB group(P<0.05). CONCLUSION Rats with ALI induced by a single low dose of PFIB exposure undergo compensatory repair except for pulmonary capacity and pulmonary ventilation functions. Early treatment with QKL reduces protein content of BALF and alleviates pulmonary edema,and has some beneficial effect on lung function recovery later.%目的：观察低剂量全氟异丁烯（PFIB）单次暴露诱发大鼠急性肺损伤（ALI）及清开灵注射液早期救治的长期效应。方法雄性Wistar大鼠224只，随机分为正常对照组（空气暴露后ip给予生理盐水10 mL·kg-1）、清开灵对照组（空气暴露后ip给予清开灵注射液10 mL·kg-1）、PFIB染毒组（PFIB 280 mg·m-3，染毒5 min，1 h后ip给予生理盐水10 mL · kg-1）和清开灵救治组（PFIB染毒后1 h ip给予清开灵注射液10 mL·kg-1），分别于染毒后24 h和3，6，12，24，36和48周随机处死8只，检测动脉血气、肺功能、肺系数、支气管肺泡灌洗液（BALF）中蛋白含量、肺组织和血浆中羟脯氨酸（HYP）含量等。结果与正常对照组相比，PFIB中毒组大鼠染毒后24 h肺系数和BALF中蛋白含量显著升高（P<0.01），动脉血氧分压PaO2（P<0.01）和氧饱和度SaO2显著降低（P<0.05），吸气时间、呼气时间、潮气量（TV）、呼气量（EV）、呼气末停顿和弛豫时间显著降低（P<0.01）；上述指标从3周开始逐渐恢复至正常水平；至48周时，TV、EV和呼气峰流量（PEF）与正常对照组相比显著降低（P<0.05）。肺组织中HYP含量在染毒后24 h与正常对照组相比降低（P<0.05），之后至6周时显著高于正常对照组（P<0.05），12周后恢复至正常水平。血浆中HYP含量在染毒后24 h与正常对照组相比升高（P<0.05），之后逐渐恢复至正常水平。清开灵治疗组大鼠染毒后24 h BALF中蛋白含量显著低于PFIB中毒组（P<0.01）；染毒后24 h至24周，TV、EV、吸气峰流量和PEF值与PFIB中毒组均无显著性差异，至48周时TV和EV均显著高于PFIB中毒组（P<0.05），恢复至正常对照组水平。结论低剂量PFIB致大鼠ALI的长期修复过程中，肺组织损伤得到代偿性修复，但肺容量和肺通气功能有所降低。清开灵早期救治可抑制PFIB-ALI急性期BALF中蛋白渗漏，并对后期肺功能恢复起到一定的作用。