摘要
背景:阻塞性睡眠呼吸暂停低通气综合征和慢性阻塞性肺疾病是呼吸系统常见疾病,二者并存发生率高,临床上称之为"重叠综合征",慢性间断性缺氧是重叠综合征的基本病变过程。目的:探讨红景天甙对慢性间断性缺氧小鼠细胞凋亡和氧化应激肺损伤的作用机制。方法:实验项目经西南医科大学动物实验伦理委员会批准。取野生型C57BL/6雄性小鼠随机分为正常对照组、红景天甙组、慢性间断性缺氧组、慢性间断性缺氧+红景天甙组,后两组模拟慢性间断性缺氧模型:即将小鼠放入缺氧舱,调节初始氧浓度8%-10%维持1min后迅速转为常氧(19%-21%)持续2min为一个完整循环,每天循环8 h,连续30 d。缺氧当天起红景天甙组、慢性间断性缺氧+红景天甙组小鼠给予红景天甙50 mg/(kg·d)灌胃处理连续30 d。光镜下观察肺组织病理变化;化学荧光法定量、定性检测小鼠肺组织氧自由基活性;Western-blot法检测肺组织凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶3(caspase-3)、Bax、Bcl-2水平及Bax/Bcl-2比值。结果与结论:(1)小鼠发生慢性间断性缺氧时激活肺氧化应激途径并启动细胞凋亡,表现为与正常对照组相比,慢性间断性缺氧组病理损伤显著,肺动脉管壁增厚,肺泡大小不均,活性氧活性升高,Bax/Bcl-2比值、caspase-3蛋白水平升高(P<0.05);而给予红景天甙处理可有效改善慢性间断性缺氧造成的小鼠肺损伤,与慢性间断性缺氧组相比,慢性间断性缺氧+红景天甙组肺病理损伤减轻,活性氧活性降低、凋亡蛋白Bax/Bcl-2比值、caspase-3水平下降(P <0.05);正常对照组与红景天甙组各项指标无明显差异(P> 0.05);(2)结果说明,红景天甙可以通过抑制氧化应激反应和细胞凋亡途径改善小鼠慢性间断性缺氧肺损伤。
BACKGROUND: Obstructive sleep apnea hypopnea syndrome and chronic obstructive pulmonary disease are common diseases in respiratory system. The incidence of coexistence is high, which is called "overlap syndrome" in clinical practice. Chronic intermittent hypoxia is the basic pathological process of overlap syndrome.OBJECTIVE: To investigate the mechanism of salidroside affecting the apoptosis and oxidative stress in lung injury caused by chronic intermittent hypoxia in mice.METHODS: The study was approved by the Ethics Committee of Laboratory Animal Center of Southwest Medical University. Wild-type C57 BL/6 male mice were randomly divided into normal control group, salidroside group, chronic intermittent hypoxia group and chronic intermittent hypoxia+salidroside group. The mice in the latter two groups were placed in an anoxic chamber. The complete cycle of hypoxia was adjusted to the initial oxygen concentration of 8% to 10% for 1 minute, and then rapidly converted to normoxia(19%-21%) for 2 minutes.The daily cycle of hypoxia was 8 hours for 30 days. On the day of hypoxia, mice in the salidrosidel and salidrosidel groups were given salidroside(50 mg/(kg·d) for 30 consecutive days. The pathological changes of lung tissue were observed under a light microscope.Quantitative and qualitative detection of oxygen free radical activity in mouse lung tissue was performed by chemical fluorescence method.The apoptosis related protein caspase-3, Bax, Bcl-2 levels, and Bax/Bcl-2 ratio were detected by western blot assay.RESULTS AND CONCLUSION:(1) The occurrence of chronic intermittent hypoxia activated the lung oxidative stress pathway and initiated cell apoptosis. The lung pathological damage in the chronic intermittent hypoxia group was more serious than that in the normal control group.Its pulmonary artery wall thickened in the normal control group, the alveolar size was uneven, the oxygen free radical activity was increased,the ratio of Bax/Bcl-2 and the protein level of caspase-3 were significantly increased(P < 0.05). However, the degree of lung pathological damage in the chronic intermittent hypoxia+salidroside group was significantly reduced and the above indicators in the chronic intermittent hypoxia+salidroside group were significantly lower than those in the chronic intermittent hypoxia group(P < 0.05). There was no significant difference in each indicator between normal control and salidroside groups(P > 0.05).(2) Therefore, salidroside may improve chronic intermittent hypoxic lung injury in mice by inhibiting oxidative stress response and apoptotic pathways.
作者
皇甫志敏
徐倩
王晓
王恩平
冯玥
曾娟
朱锐
赵春玲
Huangfu Zhimin;Xu Qian;Wang Xiao;Wang Enping;Feng Yue;Zeng Juan;Zhu Rui;Zhao Chunling(Basic Medical College,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Clinical Medical College,Southwest Medical University,Luzhou 646000,Sichuan Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2019年第31期5036-5040,共5页
Chinese Journal of Tissue Engineering Research
基金
四川省教育厅项目(2014JY0018),项目负责人:赵春玲
国家级大学生创新创业项目(201510632031),项目负责人:朱锐~~
关键词
红景天甙
慢性间断性缺氧
肺
氧化应激
凋亡
活性氧
salidroside
chronic intermittent hypoxia
lung
oxidative stress
apoptosis
oxygen free radical
