南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (09): 1277-.

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乌司他丁对重症中暑小鼠急性肺损伤的保护作用

周耿标,徐秋林,刘亚楠,王郑莲,郭晓华,苏磊   

  • 出版日期:2015-09-20 发布日期:2015-09-20

Protective effects of ulinastatin against acute lung injury induced by heatstroke in mice

  • Online:2015-09-20 Published:2015-09-20

摘要: 目的探讨乌司他丁(ulinastatin, UTI)对重症中暑小鼠急性肺损伤的保护作用。方法SPF级雄性C57/BL6小鼠60只,随
机分为6组(n=10):正常组、重症中暑模型组、造模前给药组、造模前生理盐水组、造模后给药组及造模后生理盐水组。正常组
小鼠置于(22±1)℃的环境中,其余各组小鼠置于加温舱(温度37 ℃、湿度60%)持续加温,两给药组分别于造模前、后10 min腹
腔注射UTI 5×104 U/kg,而两生理盐水组则腹腔注射等量的生理盐水,加热期间前1.5 h每隔30 min用水银温度计人工测定肛温
(Tc)1次,之后每隔15 min测1次肛温,待Tc达42.7 ℃(以此作为重症中暑开始的标志)后撤离高温舱,转移至常温中复温6 h。
观察各组肺组织病理学变化,检测各组支气管肺泡灌洗液(Bronchial Alveolar Lavage Fluid, BALF)中蛋白含量、肺湿/干比(W/
D)、肺含水量、肺血管通透性(伊文思蓝含量)。结果与正常组相比,重症中暑模型组及造模前、后生理盐水组肺部损伤严重,病
理形态学改变明显,肺W/D比值、肺含水量、BALF中蛋白含量及肺血管通透性均显著增加(P<0.05),且组间无显著性差异(P>
0.05);而造模后给药组与重症中暑模型组及造模前、后生理盐水组相比,其肺部病理变化明显改善,肺W/D值、肺含水量、BALF
中蛋白含量及肺血管通透性显著降低,但高于正常对照组(均P<0.05),而造模前给药组小鼠Tc≥42.7 ℃的时间较其它热打击组
明显延长,但上述肺损伤指标却未见明显改善。结论乌司他丁对重症中暑所致肺水肿与炎性渗出具有抑制作用,能有效对抗
重症中暑所致的急性肺损伤,发挥保护作用。

Abstract: Objective To investigate the protective effect of ulinastatin (UTI) against acute lung injury induced by heatstroke in
mice. Methods Sixty C57/BL6 mice were randomly divided into 6 groups, with 10 mice in each: control group, heatstroke
group, UTI pretreatment group, saline pretreatment group, UTI post-treatment group, saline post-treatment group. The
control mice were housed at a controlled room temperature of (22 ± 1) ℃ , and the other groups were placed inside a
temperature and humidity controlled chamber pre-set at 37 ℃ and 60%. The two UTI groups were intraperitoneally injected
with UTI at 5×104 U/kg 10 min before or after heat stress, and the two saline groups were given then equal amounts of saline in
the same manner. The core body temperature of mice was monitored by a mercury thermometer every 30 min in the first 1.5 h
during heating. The core temperature was measured, then every 15 min until it reached 42.7 ℃, which was taken as the onset
of heatstroke. The animals were allowed to recover passively at ambient temperature for 6 h. The lung histopathological
changes, protein concentration in BALF, lung wet/dry weight ratios, lung water content, and pulmonary microvascular
permeability were assayed after 6 h of recovery at 37 ℃. Results Compared with the control group, the heatstroke model
group and two saline groups displayed more severe lung damage and pathological morphology changes, and the lung wet/dry
weight ratio, protein concentration in BALF, lung water content and pulmonary microvascular permeability were also
significantly increased. These effects were significantly alleviated in UTI treated group. Pretreat ment with UTI significantly
prolonged the time to Tc≥42.7 ℃ but had no effect on lung injury induced by heatstroke. Conclusion UTI can reduce the
pulmonary edema and inflammatory exudation in acute lung injury caused by heatstroke.