中度低温对内毒素诱导急性肺损伤大鼠肺泡毛细血管膜通透性的影响

Effects of moderate hypothermia on alveolar capillary membrane permeability in endotoxin-induced acute lung injury in rats

目的探讨中度低温对脂多糖(LPS)诱导急性肺损伤(ALI)大鼠肺泡毛细血管膜通透性的影响。方法34只雄性SD大鼠,随机分为4组。腹腔注射LPS 1.0 mg·kg-1,16 h后在机械通气下气管内滴注1.5 mg·kg-1LPS(0.5 ml)方法建立ALI模型。正常对照组(C组,n=8):只给予等量的生理盐水;内毒素组(L组,n=10):给予LPS;低温组(H组,n=8):将体温降低并维持在32.5-33.0℃, 但不给予LPS;内毒素复合低温组(L+H组,n=8):给予LPS,并且当氧合指数(PaO2/FiO2)≤300mm Hg 时将体温降低并维持在32.5-33.0℃。分别于ALI时、ALI后1、2、3、4 h记录平均动脉压(MAP)和中心静脉压(CVP),同时测定动脉血气的变化。于ALI后4 h处死大鼠,检测支气管肺泡灌洗液(BALF) 中白蛋白浓度、左肺湿/干重(W/D)及肺组织髓过氧化物酶(MPO)活性,电镜下观察肺泡毛细血管膜形态结构的变化。结果L组PaO2/FiO2降低(P<0.01),PaCO2在ALI后3、4 h升高(P<0.01);与L组比较,L+H组PaO2,FiO2差异无统计学意义,但PaCO2在ALI后3、4 h降低(P<0.05)。与C组比较,L 组BALF中白蛋白浓度、W/D及肺组织MPO活性升高(P<0.01或0.05);而L+H组上述指标则较L 组下降(P<0.01或0.05)。电镜结果:C、H组肺泡毛细血管膜结构基本正常;L组毛细血管内皮明显剥脱;而L+H组毛细血管内皮剥脱程度较L组减轻。结论中度低温对ALI大鼠可通过减轻肺内PMN聚集,降低肺泡毛细血管膜通透性,在一定程度上减轻了肺损伤。

Objective To investigate the effects of moderate hypothermia on the permeability of alveolar capillary membrane in acute lung injury （ALI） induced by lipopolysaccharide （LPS）.Methods Thirty-four adult male SD rats weighing 300-350g were randomly divided into 4 groups： control group （ n = 8） ; LPS group （ n =10） ; hypothermia group （ n = 8） and LPS ＋ hypothermia group （ n = 8）. The animals were anesthetized with intraperitoneal （ i. p. ） 1% pentobarbital 30 mg· kg^-1 , intubated and mechanically ventilated （ RR 80 bpm, Vτ 20ml· kg^ - 1 , I：E 1：2 ）. Right external jugular vein and left carotid artery were cannulated for BP and CVP monitoring and blood sampling. ALI was induced by LPS 1.0 mg·kg^-1 i.p. and 16h later, intratracheal instillation of LPS 1.5 mg·kg^-1. ALI was considered established when PaO2/FiO2 ≤ 300. Hypothermia was induced by surface cooling. Body T0 was reduced to 32.5-33.0℃ . In control and hypothermia groups normal saline was given instead of LPS. Arterial blood samples were taken for blood gas analysis and MAP and CVP were recorded before （ To,baseline） and 1, 2, 3, 4 h after ALI （T1-4） . At the end of experiment （4 h after ALI was established） the animals were killed by exsanguination. The lungs were removed. Lung lavage was performed and the concentration of albumin in bronchoalveolar lavage fluid （BALF）, the left lung wet/dry weight ratio, myeloperoxidase （MPO）activity of lung tissue were measured. Lung tissue was also taken for histologic examination by transmission electron microscopy. Results There was no significant difference in hemodynamics among the 4 groups. PaO2/FiO2 and PaCO2 remained unchanged in the control group and hypothermia group. PaO,/FiO2 was significantly decreased and PaCO2 was significantly increased as compared to the baseline values （ T0） in LPS group （ P 〈 0. 01 ） .Hypothermia inhibited the increase in PaCO2 but had no effect on the decrease in PaO2/FiO2 induced by LPS. LPS significantly increased the lung W/D weight ratio, the concentration of albumin in BALF and MPO activity of the lung tissue as compared with the control group （P 〈 0.01 or 0.05）. Moderate hypothermia significantly reduced the increase in lung W/D ratio, albumin concentration in BALF and lung tissue MPO activity induced by LPS but the lung W/D weight ratio in LPS ＋ hypothermia group was still significantly higher than that in control group （ P 〈0.05）. Electron microscopic examination showed that the alveolar capillary membrane was severely damaged in LPS group and moderate hypothermia significantly attenuated the injury to the alveolar capillary membrane.Conclusion Moderate hypothermia significantly decreases the increased permeability of alveolar capillary membrane in a rat model of ALI induced by LPS.