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高碳酸血症对急性肺损伤保护作用及机制探讨的实验研究
The protective effects and mechanism of hypercapnia on acute lung injury
【摘要】 目的探讨高碳酸血症对急性肺损伤模型的保护作用及可能的机制。方法 24只新西兰兔按随机数字表法分为对照组、治疗组、预防组,每组8只。采用脂多糖静脉注射复制肺损伤模型,观察3组兔血流动力学、血气指标的变化;检测肺组织湿/干重(W/D)比、光镜、肺损伤组织学定量评价指标(IQA)来评估肺脏的损伤程度。通过对肺组织中髓过氧化物酶(MPO)、丙二醛(MDA)及血清和支气管肺泡灌洗液(BALF)中白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)浓度及中性粒细胞凋亡率的测定,阐明高碳酸血症对肺损伤保护的可能机制。结果 (1)治疗组、预防组在模型形成后平均动脉压、心率、动脉血二氧化碳分压(PaCO2)、动脉血氧分压/吸入气氧浓度(PaO2/FiO2)分别为(79±6)mm Hg(1 mm Hg=0.133 kPa)、(180±10)次/min、(99±13)mm Hg、250±26,(80±9)mm Hg、(181±12)次/min、(95±11)mm Hg、241±56,与对照组[(66±10)mm Hg、(139±13)次/min、(31±4)mm Hg、182±35]比较差异有统计学意义(t 值分别为4.05、26.32、5.36、28.15、12.54、11.07、16.13、12.36,P 均分别<0.05、0.01);(2)治疗组、预防组 W/D、MPO、MDA 分别为1.98±0.28、1.87±0.30、(6.1±1.6)U/g、(5.8±1.5)U/g、(20±5)mg/L、(19±4)mg/L,与对照组[2.43±0.26、(9.0±1.3)U/g、(36±8)mg/L]比较差异有统计学意义(t 值分别为11.07、24.46、2.35、9.63,12.34、25.32,P 分别<0.05、0.01);(3)治疗组、预防组血清和 BALF 中 IL-8、TNF-α、中性粒细胞凋亡率分别为(50±8)ng/ml、(103±49)ng/ml、(94±16)ng/ml、(44±9)ng/ml、(38±9)%、(56±5)%、(49±7)ng/ml、(96±50)ng/ml、(91±14)ng/ml、(39±6)ng/ml、(39±10)%、(55±10)%,与对照组[(91±43)ng/ml、(177±60)ng/ml、(162±15)ng/ml、(67±7)ng/ml、(19±7)%、(43±7)%]比较差异有统计学意义(t 值分别为7.12、5.55、7.30、3.93、13.08、8.00,P 分别<0.05、0.01);(4)各组血清及 BALF 中 IL-8、TNF-α与中性粒细胞凋亡率呈负相关(r 值分别为-0.73、-0.72、-0.52、-0.64、-0.73、-0.56、-0.57、-0.78、-0.69、-0.75、-0.82、-0.84,P 均<0.05)。结论高碳酸血症对急性肺损伤具有保护作用,对血流动力学无明显影响。
【Abstract】 Objective To explore the protective effects of hypercapnia on acute lung injury(ALI) and the possible mechanisms.Methods Twenty-four healthy New Zealand white rabbits were involved in this study,and randomly divided to three groups,a control group,a therapeutic group,and a prophylactic group(n=8,each).Lipopolysaccharide(1 mg/kg)was injected intravenously to establish the ALI model. Blood gas analysis and artery pressure were monitored.IL-8 and TNF-α in the serum and bronchoalveolar lavage fluid(BALF),wet weight/dry weigh(W/D),index of quantitative assessment of histological lung injury(IQA),myeloperoxidase(MPO)and malondialdehyde(MDA)activity in the lung tissue were measured.Apoptosis index of neutrophils were determined.Results(1)The mean artery pressure,heart rate,PaCO2,and PaO2/FiO2 changed in the ALI model of the therapeutic group and the prophylactic group [(79±6)mmHg(1 mm Hg=0.133 kPa),(180±10)/min,(99±13)mm Hg,250±26,(80±9) mm Hg,(181±12)/min,(95±11)mm Hg,241±256,respectively].In the control group,they were (66±10)mm Hg,(139±13)/min,(31±4)mm Hg,182±35,respectively.The differences were significant compared with the control group(t=4.05,26.32,5.36,28.15,12.54,11.07,16.13,12.36,P< 0.05,0.01).(2)The levels of W/D,MPO,and MDA in the therapeutic group and the prophylactic group were 1.98±0.28,1.87±0.30,(6.1±1.6)U/g,(5.8±1.5)U/g,(20±5)mg/L,(19±4)mg/L; while in the control group,they were[2.43 + 0.26,(9.0±1.3)U/g,(36±8)mg/L]respectively.The difference was significant(t=11.07,24.46,2.35,9.63,12.34,25.32,P<0.05,0.01).(3)The levels of IL-8 and TNF-α in the serum and BALF and the apoptosis index in the three groups were(50±8)ng/ml, (103±49)ng/ml,(94±16)ng/ml,(44±9)ng/ml,(38±9)%,(56±5)%,(49±7)ng/ml, (96±50)ng/ml,(91±14)ng/ml,(39±6)ng/ml,(39±10)%,(55±10)%,(91±43)ng/ml, (177±60)ng/ml,(162±15)ng/ml,(67±7)ng/ml,(19±7)%,(43±7)%,respectively.The difference was significant among the three groups(t=7.12,5.55,7.30,3.93,13.08,8.00,P<0.05,0.01 respectively).(4)The apoptosis index of neutrophils was negatively correlated with the levels of IL-8 in the serum and BALF(r=-0.73,-0.72,-0.52,-0.64,-0.73,-0.56,all P<0.05),and the levels of TNF-α in the serum and BALF(r=-0.57,-0.78,-0.69,-0.75,-0.82,-0.84,all P<0.05). Conclusion Hypercapnia does not affect hemodynamies and has protective effects on ALl.
【Key words】 Lung injury,acute; Hypercapnia; Myeloperoxidase; Malondialdehyde; Neutrophil; Cytokine;
- 【文献出处】 中华结核和呼吸杂志 ,Chinese Journal of Tuberculosis and Respiratory Diseases , 编辑部邮箱 ,2007年10期
- 【分类号】R563.8
- 【被引频次】2
- 【下载频次】21