不引起肺动脉高压的间歇性低氧心肌保护条件优化研究
Study on optimization of myocardial protection conditions for intermittent hypoxia without pulmonary hypertension
焦媛媛 1卢林鹤 2周海涛 3李慢 1刘超阳 1张文 1裴建明 1付锋1
作者信息
- 1. 空军军医大学 基础医学院生理与病理生理学教研室 陕西西安 710032
- 2. 空军军医大学 基础医学院生理与病理生理学教研室 陕西西安 710032;空军军医大学 西京医院心脏外科 陕西西安 710032
- 3. 空军军医大学 西京医院心脏外科 陕西西安 710032
- 折叠
摘要
目的 本研究拟寻求不引起肺动脉高压的间歇性低氧心肌保护条件.方法 成年雄性C57BL/6小鼠随机分为常氧对照组(大气压 101.3 kPa,氧浓度约为 21 ml/L)、3 000 m低氧组(大气压 70.7 kPa,氧浓度约为 14.2 ml/L)、4 000 m低氧组(大气压 61.3 kPa,氧浓度约为 12.6 ml/L)、5 000 m低氧组(大气压 53.9 kPa,氧浓度约为11.3 ml/L)四组,每天 4h.经肋间肌穿刺检测右心室收缩压以反映肺动脉压力变化,心肌缺血再灌注后,使用伊文思蓝-TTC双染检测心梗面积,ELISA试剂盒检测血清心肌肌钙蛋白I含量.结果 与常氧对照组相比,3 000 m低氧组小鼠右心室收缩压在低氧 1周和 2周无明显变化,在第 3周开始升高(P<0.05),而 4 000 m、5 000 m低氧组小鼠低氧 1周右心室收缩压即升高(P<0.01).小鼠常氧或 3 000m低氧 2周处理后,分别建立在体与离体心肌缺血再灌注模型,与常氧组相比,低氧处理组在体与离体心肌缺血再灌注后均表现为梗死面积减小,血清心肌肌钙蛋白I含量降低(P<0.01).恢复常氧 4周后,3 000 m低氧 2周的心肌保护作用丧失.结论 不引起肺动脉高压的间歇性低氧心肌保护条件是3 000m低氧处理2周,每天4h,该保护效果可在脱离低氧环境后维持3周.
Abstract
AIM To identify intermittent hypoxic conditions that provide myocardial protection without causing pulmonary hypertension.METHODS Adult male C57 mice were randomly assigned to the normal oxygen control group and groups exposed respectively to hypoxia at altitudes of 3000 m,4000 m and 5000 m for a duration of 4 hours per day.Intercostal puncture was performed to measure the right ventricular systolic pressure as an indicator of pulmonary artery pressure changes.Following myocardial ischemia-reperfusion,the extent of myocardial infarction was assessed using Evans blue-TTC double staining and serum troponin I levels were measured using ELISA.RESULTS Compared with that in the normal oxygen control group,there was no significant change in right ventricular systolic blood pressure in the mice exposed to hypoxia at 3000 m during the first two weeks.However,an increase was observed starting from the third week(P<0.05).In contrast,mice exposed to hypoxia at 4000 m and 5000 m showed increased right ventricular systolic blood pressure after one week of exposure(P<0.01).Mice treated with either normal oxygen or hypoxia at 3000 m for two weeks underwent in vivo myocardial ischemia-reperfusion or isolated myocardial ischemia-reperfusion models,respectively.Both groups exhibited reduced infarct size and decreased serum troponin I content compared with those in the normal oxygen group(P<0.01).Four weeks after returning to a normal oxygen environment,the protective effect provided by hypoxic treatment was lost.CONCLUSION The intermittent hypoxic myocardial protection condition,achieved through a 2-week treatment of hypoxia at an altitude of 3000 m for 4 hours daily,does not induce pulmonary hypertension.Furthermore,the protective effect persists for up to 3 weeks after discontinuation of the hypoxic environment.
关键词
心肌缺血再灌注损伤/间歇性低氧/肺动脉高压/心肌保护/常氧Key words
myocardial ischemia-reperfusion injury/intermittent hypoxia/pulmonary hypertension/myocardial protection/normoxia引用本文复制引用
基金项目
陕西省国际合作重点项目(2022KWZ-18)
国家自然科学基金项目(82070051)
国家自然科学基金项目(82070387)
出版年
2024