HIF-1α/EphrinA1信号通路在糖尿病因素削弱七氟醚心肌保护中的作用机制  

Role of HIF-1α/EphrinA1 signaling pathway in diabetic factors impairing myocardial protection of sevoflurane and its mechanism

作　　者：张佩 贺建东[2] 韩冲芳[2] 杨文曲[2] 邓捷[1] ZHANG Pei;HE Jiandong;HAN Chongfang;YANG Wenqu;DENG Jie(College of Anaesthesiology,Shanxi Medical University,Taiyuan 030001,China;Department of Anesthesiology,Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences)

机构地区：[1]山西医科大学麻醉学院麻醉教研室,太原030001 [2]山西医学科学院,山西白求恩医院麻醉科

出　　处：《山西医科大学学报》2021年第8期995-1000,共6页Journal of Shanxi Medical University

基　　金：山西大医院优秀青年启动项目(2019YJ11)。

摘　　要：目的探讨七氟醚对糖尿病大鼠心肌缺血再灌注损伤的影响及其与HIF-1α/EphrinA1信号通路的关系。方法健康成年雄性SD大鼠,体质量210-260 g,采用腹腔注射50 mg/kg链脲佐菌素联合高脂高糖饲料持续喂养8周的方法制备2型糖尿病大鼠模型。取造模成功的60只糖尿病大鼠,按照随机数字表法分为5组(n=12):假手术组(sham组)、心肌缺血再灌注组(I/R组)、七氟醚后处理组(SP组)、HIF-1α激活剂DMOG组(DMOG组)、HIF-1α激活剂DMOG加七氟醚后处理组(DMOG+SP组)。sham组在心脏左冠脉前降支只穿线不结扎,其余各组采用结扎左冠脉前降支30 min,再灌注120 min的方法制备心肌缺血再灌注损伤模型。DMOG组在手术前24 h腹腔注射DMOG 40 mg/kg。DMOG+SP组在松开结扎线的前5 min吸入2.5%的七氟醚维持15 min。再灌注120 min时取下心肌组织,TTC染色测量心肌梗死面积,光镜下观察心肌细胞病理学损伤,采用免疫荧光共定位观察HIF-1α、EphrinA1的位置,采用Western blot检测HIF-1α、EphrinA1蛋白含量。结果与sham组相比,其余4组心肌梗死面积增大(P<0.05),病理学损伤加重,HIF-1α、EphrinA1蛋白表达下调(P<0.05)。与I/R组相比,DMOG组和DMOG+SP组心肌梗死面积缩小(P<0.05),病理学损伤减轻,HIF-1α、EphrinA1蛋白表达上调(P<0.05)。SP组与I/R组相比上述指标差异无统计学意义(P>0.05)。与DMOG组相比,DMOG+SP组心肌梗死面积缩小(P<0.05),病理学损伤减轻,HIF-1α和EphrinA1蛋白表达上调(P<0.05)。免疫荧光共定位显示:HIF-1α和EphrinA1均分布于心肌细胞的细胞质上,且二者存在共定位的关系。结论七氟醚的心肌保护作用在糖尿病合并心肌缺血再灌注损伤大鼠模型中消失可能与糖尿病因素抑制HIF-1α/EphrinA1信号传导通路有关。Objective To investigate the effect of sevoflurane on myocardial ischemia-reperfusion injury in diabetic rats and its relationship with HIF-1α/EphrinA1 signaling pathway.Methods Healthy adult male SD rats with body weight of 210-260 g were treat-ed with intraperitoneal injection of 50 mg/kg streptozotocin combined with high fat and high sugar diet for 8 weeks to establish type 2 diabetic models.Sixty diabetic rats were selected and divided into five groups according to random number table method(n=12):sham operation group(sham group),myocardial ischemia reperfusion group(I/R group),sevoflurane posttreatment group(SP group),HIF-1αactivator DMOG group(DMOG group),HIF-1αactivator DMOG plus sevoflurane posttreatment group(DMOG+SP group).In sham group,the left anterior descending coronary branch of the heart was only threaded but not ligated.In the other groups,the left anterior descending coronary branch of the heart was ligated for 30 min and reperfused for 120 min to prepare the myocardial ischemia reperfusion injury model.In DMOG group,the rats were intraperitoneally injected with 40 mg/kg DMOG at 24 h before operation.In DMOG+SP group,the rats were treated with inhalation of 2.5%sevoflurane for 15 min at 5 min before loosening the ligation line.Myocardial tissue was taken at 120 min after reperfusion,and the myocardial infarction area was measured by TTC staining.Pathological damage of myocardial cells was observed under light microscopy.The positions of HIF-1αand ephrinA1 were observed by immunofluorescence co-localization,and the protein levels of HIF-1αand EphrinA1 were detected by Western blot.Results Compared with sham group,the myocardial infarction area was increased in the other four groups(P<0.05),the pathological injury was aggravated,and the expression of HIF-1αand EphrinA1 proteins were down-regulated(P<0.05).Compared with I/R group,the myocardial infarction area and pathological damage were reduced in DMOG group and DMOG+SP group(P<0.05),and the expression levels of HIF-1αand EphrinA1 proteins

关 键 词：七氟醚 糖尿病 心肌缺血再灌注损伤 低氧诱导因子 

分 类 号：R363[医药卫生—病理学]