慢性低氧性肺动脉高压大鼠动脉血气分析指标的变化及其意义

doi:10.12300/j.issn.1674-5817.2020.080

摘要/Abstract

摘要： 目的探讨慢性低氧诱导的低氧性肺动脉高压大鼠模型中动脉血气分析指标的变化及意义。方法随机将36只SD雄性大鼠分为常氧对照组和低氧（1、3、7、14和21 d）组,低氧组置于低氧舱（O₂体积分数为10％）相应的天数。采用右心导管法测定右心室收缩压（RVSP）,计算右心室（RV）与左心室（LV）+室间隔（S）质量比值,得出右心室肥厚指数（RVHI）。采用Masson染色法观察肺动脉病理结构改变。经腹主动脉取血进行动脉血气分析,测定指标包括酸碱度（pH）、动脉血二氧化碳分压（PaCO₂）、动脉血氧分压（PaO₂）、动脉血氧饱和度（SaO₂）、碳酸氢盐（HCO₃^–）、钠离子（Na⁺）、钾离子（K⁺）、钙离子（Ca²⁺）、血细胞比容（Hct）和血红蛋白（Hb）。结果低氧各组大鼠RVSP和RVHI均明显高于常氧对照组（P<0.05）。与常氧对照组相比,低氧（7、14、21 d）组大鼠肺动脉异常重塑。与常氧对照组相比,低氧各组pH和HCO₃^–含量均明显降低（P<0.05）,低氧21 d组PaCO₂显著增高（P<0.05）,低氧14 d组PaO₂和SaO₂均明显降低（P<0.05）,除低氧1 d外各组Na⁺浓度和低氧3 d组Ca²⁺浓度明显降低（P<0.05）,除低氧14 d外各组K⁺浓度显著升高（P<0.05）,低氧各组Hct和Hb水平均明显升高（P<0.05）。低氧性肺动脉高压大鼠动脉血气分析中Na⁺水平与RVSP呈负相关（P<0.05）。结论低氧性肺动脉高压大鼠动脉血气分析指标pH、PaCO₂、PaO₂、SaO₂、HCO₃^–、Na⁺、K⁺、Ca²⁺、Hct和Hb发生明显变化,参与并调控低氧性肺动脉高压的发生发展,其中Na⁺水平可能成为间接评估低氧性肺动脉高压严重程度的指标。

关键词: 慢性低氧, 肺动脉高压, 血管重塑, 血气分析, 大鼠

Abstract: Objective To investigate the changes and significance of arterial blood gas analysis indexes in a rat model of pulmonary hypertension induced by chronic hypoxia. Methods Thirty-six SD male rats were randomly divided into the normoxic control group and the hypoxic groups. The rats in the hypoxic groups were placed in a hypoxic chamber (10% oxygen concentration) for 1, 3, 7, 14, 21 days, respectively. Right ventricular systolic pressure (RVSP) was measured by right ventricular catheter, and right ventricular hypertrophy index (RVHI) was calculated by calculating the weight ratio of right ventricle (RV) to [left ventricle (LV) + ventricular septum (S)]. Masson staining was used to observe the pathological changes of pulmonary artery. Blood was taken from the abdominal aorta for the arterial blood gas analysis to determine the following indexes: pondus hydrogenii (pH), arterial partial pressure of carbon dioxide (PaCO₂), arterial partial pressure of oxygen (PaO₂), arterial oxygen saturation (SaO₂), bicarbonate (HCO₃^–), sodium (Na⁺), potassium (K⁺), calcium (Ca²⁺), hematocrit (Hct) and hemoglobin (Hb). Results RVSP and RVHI of the rats were significantly increased in the hypoxic groups compared with the normoxic control group (P<0.05). Compared with the normoxic control group, the hypoxic groups (7, 14, 21 days) had abnormal pulmonary artery remodeling. Compared with the normoxic control group, the pH and HCO₃^– levels of the hypoxic groups were significantly reduced (P<0.05); PaCO₂ level was significantly increased in the hypoxic 21-day group (P<0.05), PaO₂ and SaO₂ levels were significantly decreased in the hypoxic 14-day group (P<0.05), the Na⁺ concentration (except hypoxia 1-day group) and the Ca²⁺ concentration (hypoxic 3-day group) were significantly reduced (P<0.05); the K⁺concentrations were increased significantly in the hypoxic groups (except hypoxia 14-day group) (P<0.05); Hct and Hb were significantly increased in the hypoxic groups (P<0.05). There was a significant negative correlation between Na⁺ and RVSP in rats with hypoxic pulmonary hypertension (P<0.05). Conclusion The arterial blood gas analysis indexes, including pH, PaCO₂, PaO₂, SaO₂, HCO₃^–, Na⁺, K⁺, Ca²⁺, Hct and Hb are significantly changed, and participate in and regulate the development and progression of hypoxic pulmonary hypertension in rats, in which Na⁺ level may be used as an indicator to evaluate the severity of hypoxic pulmonary hypertension indirectly.

Key words: Chronic hypoxia, Pulmonary hypertension, Vascular remodeling, Blood gas analysis, Rats

中图分类号:

Q95-33

张舒婷, 姚青青, 李宜珊, 施熠炜. 慢性低氧性肺动脉高压大鼠动脉血气分析指标的变化及其意义[J]. 实验动物与比较医学, 2021, 41(1): 27-32.

ZHANG Shuting, YAO Qingqing, LI Yishan, SHI Yiwei. Changes and Significance of Arterial Blood Gas Analysis Indexes in Rats with Chronic Hypoxic Pulmonary Hypertension[J]. Laboratory Animal and Comparative Medicine, 2021, 41(1): 27-32.

图/表 6

参考文献

[1] SALIM Y, ANASTASIA N, THEO T.Clinical update on pulmonary hypertension[J]. J Invest Med, 2020, 68(4):821-827. DOI:10.1136/jim-2020-001291.
[2] BURGER C D.Pulmonary hypertension in COPD: A review and consideration of the role of arterial vasodilators[J]. COPD, 2009, 6(2):137-144. DOI:10.1080/15412550902754252.
[3] STEINFELDERVISSCHER J, WEERWIND P W, TEERENSTRA S, et al.Reliability of point-of-care hematocrit, blood gas, electrolyte, lactate and glucose measurement during cardio pulmonary bypass[J]. Perfusion, 2006, 21(1):33-37. DOI:10.1191/0267659106pf846oa.
[4] 邹丽珍, 陈马云, 黄晓颖, 等. 改良右心导管法测量大鼠肺动脉压力的实验方法研究[J]. 中国病理生理杂志, 2014, 30(4):757-762. DOI:10.3969/j.issn.1000-4718.2014.04.033.
[5] MONTANI D, CHAUMAIS M C, GUIGNABERT C, et al.Targeted therapies in pulmonary arterial hypertension[J]. Pharmacol Ther, 2014, 141(2):172-191. DOI:10.1016/j.pharmthera.2013.10.002.
[6] TELLO K, GALL H, RICHTER M, et al.Right ventricular function in pulmonary (arterial) hypertension[J]. Herz, 2019, 44(6):509-516. DOI:10.1007/s00059-019-4815-6.
[7] 刘玉文, 范晓云, 陈冰, 等. 慢性阻塞性肺疾病伴急性加重继发肺动脉高压患者的相关危险因素分析[J]. 临床肺科杂志, 2016, 21(1):46-50. DOI:10.3969/j.issn.1009-6663.2016.01.014.
[8] 郭晓慧, 赵言廷, 徐赫男, 等. 超敏C- 反应蛋白、D- 二聚体、纤维蛋白原及血气分析与慢性阻塞性肺疾病合并肺动脉高压的相关性[J]. 中国老年学杂志, 2017, 37(3):650-652. DOI:10.3969/j.issn.1005-9202. 2015.10.074.
[9] 林国栋, 李春华, 黄海忠. 重症喘息性疾病合并肺动脉高压患儿动脉血气指标变化及其临床意义[J]. 黑龙江医学杂志, 2015, 39(5):497-499. DOI:10.3969/j. issn.1004-5775.2015.05.013.
[10] M LANIE L, V RONIQUE C, Andrea O, et al. Ion channels in pulmonary hypertension: A therapeutic interest[J]. J Mol Sci, 2018, 9(10):1-49. DOI:10.3390/ijms19103162.
[11] RIOS E J, FALLON M, WANG J, et al.Chronic hypoxia elevates intracellular pH and activates Na+/H+ exchange in pulmonary arterial smooth muscle cells[J]. Am J Physiol Lung Cell Mol Physiol, 2005, 289(5):L867-L874. DOI:10.1152/ajplung.00455.2004.
[12] SHIMODA L A, SHAM J S, SHIMODA T H, et al.L-type Ca²+ channels, resting [Ca²+]_i, and ET-1-induced responses in chronically hypoxic pulmonary myocytes[J]. Am J Physiol Lung Cell Mol Physiol, 2000, 279(5):L884-894. DOI:10.1152/ajplung. 2000.279.5.L884.
[13] 朱增民. 红细胞压积对全血黏度关系的影响研究[J]. 当代医学, 2011, 17(29):20-21. DOI:10.3969/j.issn.1009-4393.2011.29.011.
[14] 陈泳华, 曾军, 刘春丽, 等. COPD合并肺动脉高压疾病危险因素分析[J]. 广州医药, 2018, 49(5):74-77. DOI:10. 3969 /j. issn.1000-8535.2018.05.018.
[15] 杜发茂, 刘娟丽, 高芬. 肺动脉高压大鼠重返平原血红蛋白、平均肺动脉压的变化[J]. 中国医药导报, 2012, 9(30):21-26. DOI:1673-7210(2012)10(c)-0021-03.
[16] KASPERSKA A, ZEMBRON-LACNY A.The effect of intermittent hypoxic exposure on erythropoietic response and hematological variables in elite athletes[J]. Physiol Res, 2020, 69(2):283-290. DOI:10.33549/physiolres.934316.
[17] ARIAS S J, SALDANA M.The terminal portion of the pulmonary arterial tree in people native to high altitudes[J]. Circ, 1963, 28(5):915-925. DOI: 10.1161/01.cir.28.5.915.