高原低氧环境下心脏功能改变及其与自噬蛋白活化的关系  

High altitude hypoxia induces the changes of cardiac function and its relationship with autophagy protein activation

作　　者：孙海霞[1] 李方 苏玉鑫 曹宁[1] Sun Haixia;Li Fang;Su Yuxin(Dept of Cardiovascular Ultrasound,Qinghai Provincial People′s Hospital,Xining 810007)

机构地区：[1]青海省人民医院心血管超声室,西宁810007

出　　处：《安徽医科大学学报》2021年第6期898-903,共6页Acta Universitatis Medicinalis Anhui

基　　金：青海省卫生健康委员会指导性计划项目(编号:2019-wjzdx-46)。

摘　　要：目的评估长期暴露于高原低氧环境(HAH)对大鼠心脏功能的影响,并探讨其作用机制是否与单磷酸腺苷激活的蛋白激酶(AMPK)途径介导的心肌纤维化进程中自噬活性有关。方法50只雄性SD大鼠大鼠被安置在4500 m海拔高度,分别在饲养第0、1、2、4、8周随机选取10只大鼠进行体质量、血压、超声心动图、心脏组织学和自噬蛋白检查。另取30只大鼠随机分为对照组和雷帕霉素组。雷帕霉素组每天定时通过腹腔注射雷帕霉素1 mg/kg。对照组腹腔注射相同体积的0.9%氯化钠溶液。分别在试验前和第8周试验结束时进行上述检查。结果体质量、血压、超声心动图检查结果显示,HAH环境暴露导致大鼠的收缩压、体质量、右室舒张末内径(RVEDd)、左室射血分数(LVEF)增加,肺动脉加速时间(PAAT)则降低,雷帕霉素的运用逆转了这些变化。组织学分析显示,HAH环境暴露导致大鼠出现心肌变性、坏死和纤维化,伴有单核细胞浸润,并且心脏心肌纤维化增加,雷帕霉素的运用减轻了这些变化。Western blot分析显示,HAH环境暴露导致大鼠心脏组织自噬基因(Beclin-1)、微管相关蛋白轻链3(LC3)-Ⅱ/Ⅰ和AMPK蛋白在第4周增加,并达到峰值水平,但在第8周后受损。雷帕霉素的运用提高了自噬相关标记物Beclin-1、LC3-Ⅱ/Ⅰ和AMPK蛋白表达。结论长期暴露于HAH环境可破坏大鼠心脏功能,其作用机制与AMPK途径介导的心肌纤维化进程中自噬活性有关。Objective To evaluate the effects of long-term exposure to high altitude hypoxia(HAH)on cardiac function in rats,and to explore whether the mechanism is related to autophagy in the process of myocardial fibrosis mediated by AMPK pathway.Methods Fifty male SD rats were housed at an altitude of 4500 m.Ten rats were randomly selected for body weight,blood pressure,echocardiography,cardiac histology and autophagy protein examination at baseline,1 week,2 weeks,4 weeks and 8 weeks.Thirty rats were randomly divided into two groups with 15 animals in each group,including control group and rapamycin group.Rapamycin group was administered by intraperitoneal injection[1 mg/(kg·d)].The control group was intraperitoneally injected with the same volume of normal saline.The above examinations were carried out before the test and at the end of the 8th week.Results Body weight,blood pressure and echocardiography showed that the systolic blood pressure,body weight,right ventricular end diastolic diameter(RVEDd)and left ventricular ejection fraction(LVEF)of rats exposed to HAH environment increased,while the pulmonary artery acceleration time(PAAT)decreased.Rapamycin reversed these changes.Histological analysis showed that the rats exposed to HAH environment had myocardial degeneration,necrosis and fibrosis,accompanied by monocyte infiltration,and increased myocardial fibrosis.Rapamycin reduced these changes.Western blot analysis showed that the Beclin-1,LC3-Ⅱ/Ⅰand AMPK protein increased significantly up to 4 weeks,but were impaired after 8 weeks of HAH treatment in heart tissue.Rapamycin increased autophagy related markers Beclin-1,LC3-Ⅱ/Ⅰand AMPK protein expression.Conclusion Long term exposure to HAH may damage cardiac function in rats,and its mechanism is related to autophagy in the process of myocardial fibrosis mediated by AMPK pathway.

关 键 词：高原低氧 心脏功能 自噬 大鼠 雷帕霉素 

分 类 号：R339.5[医药卫生—人体生理学]