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

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（1mmHg=0．133kPa）、（180±10）次／min、（99±13）mmHg、250±26，（80±9）mmHg、（181±12）次／min、（95±11）mmHg、241±56，与对照组[（66±10）mmHg、（139±13）次／min、（31±4）mmHg、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、NPO、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。

The protective effects and mechanism of hypercapnia on acute lung injury

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-alpha 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) mm Hg (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+/-56, 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-alpha 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-alpha 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 hemodynamics and has protective effects on ALI.