基于β2AR2βarrestin2NFκB通路的地佐辛对心肌缺血再灌注损伤大鼠的作用及机制  

Effect of dezocine on myocardial ischemia-reperfusion injury in rats based on β 2AR/β arrestin2/NFκB pathway and its mechanism

作　　者：闫照虹 喻倩 李娟 张芳芳 刘伟娜 YAN Zhaohong;YU Qian;LI Juan;ZHANG Fangfang;LIU Weina(Department of Anesthesiology, Tangdu Hospital of Air Force Military Medical University, Xi'an 710038, China)

机构地区：[1]空军军医大学唐都医院麻醉科,陕西西安710038

出　　处：《西部医学》2022年第1期9-15,20,共8页Medical Journal of West China

基　　金：国家自然科学基金(81801391)。

摘　　要：目的探讨地佐辛对心肌缺血再灌注损伤大鼠β2肾上腺素受体(β2AR)/β-抑制蛋白2(β-arrestin2)/核转录因子-κB(NF-κB)通路及心肌凋亡的影响。方法60只大鼠随机分为假手术组(Sham组),心肌缺血再灌注模型组(MIRI组),地佐辛高、中、低剂量组(20、10、5 mg/kg),每组12只。地佐辛各剂量组在造模前30 min经股静脉注射相应剂量的地佐辛,Sham组和MIRI组给予等量生理盐水,采用手术结扎大鼠冠状动脉左前降支的方法复制大鼠MIRI模型。再灌注2 h后,检测各组大鼠心率(HR)、左心室收缩压(LVSP)、左心室舒张末(LVEDP),评价心脏功能;并检测血清中肌酸激酶(CK)、肌酸激酶同工酶MB(CKMB)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)水平;HE染色观察左心室组织学变化;TUNEL染色观察心肌细胞凋亡情况,计算凋亡指数;免疫组织化学法检测心肌组织Bcl-2、Bax、Caspase-3的蛋白表达;Western blot检测心肌组织β2AR、β-arrestin2、IκBα、NF-κB p65蛋白表达。结果心肌组织病理学可见,Sham组心肌纤维完整、排列整齐,MIRI组心肌严重受损,局部肌纤维横纹消失,大量炎性细胞浸润;与Sham组相比,各治疗组明显好转。与Sham组相比,MIRI组大鼠HR、LVSP、Bcl-2/Bax比值、心肌组织β2AR、β-arrestin2、IκBα蛋白表达显著降低,各治疗组较MIRI组明显升高(均P<0.05);与Sham组相比,MIRI组LVEDP、血清CK、CK-MB、TNF-α、IL-6水平、心肌组织Bcl-2、Bax、Caspase-3、NF-κB p65蛋白表达、心肌细胞凋亡率显著升高,各治疗组较MIRI组明显降低(均P<0.05)。结论地佐辛可抑制炎症反应,减少心肌细胞凋亡,对MIRI大鼠具有保护作用;其作用机制可能与上调β2AR、β-arrestin2、IκBα的表达,降低NF-κB p65表达有关。Objective To investigate the effects of dezocine onβ2-adrenergic receptor(β2AR)/β-arrestin2/nuclear factor-κB(NF-κB)pathway and myocardial apoptosis in rats with myocardial ischemia-reperfusion injury.Methods Sixty rats were randomly divided into sham operation group(Sham group),myocardial ischemia-reperfusion injury model group(MIRI group),high-,medium-and low-dose dezocine groups(20,10,5mg/kg),with twelve rats in each group.30 minutes before modeling,each treatment group was injected with the corresponding dose of dezocine via femoral vein,and the Sham group and MIRI group were given the same amount of normal saline.Except for the sham operation group,the other groups were given the method of surgical ligation of the left anterior descending coronary artery to establish a rat MIRI model.After 2 hours of reperfusion,the heart rate(HR),left ventricular systolic pressure(LVSP)and left ventricular end diastolic(LVEDP)of rats were measured to evaluate cardiac function.The serum levels of creatine kinase(CK),creatine kinase isoenzyme MB(CKMB),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were detected.The histological changes of left ventricle were observed by hematoxylin eosin(HE)staining.The apoptosis of myocardial cells were observed and the apoptosis index was calculated by TUNEL staining.The protein expression of Bcl-2,Bax,and caspase-3 was detected by immunohistochemistry.The protein expression ofβ2AR,β-arrestin2,IκBα,and NF-κB p65 was detected by Western blot.Results Myocardial histopathology showed that the myocardial fibers in Sham group were complete and arranged neatly,while the myocardium in MIRI group was seriously damaged.The local muscle fibers disappeared and a large number of inflammatory cells infiltrated.Compared with Sham group,each treatment group improved obviously.Compared with Sham group,the HR,LVSP,Bcl-2/Bax ratio,protein expression ofβ2AR,β-arrestin2,IκBαin myocardial tissues in MIRI group were significantly lower(P<0.05),and those in each treatment group were signific

关 键 词：心肌缺血再灌注损伤 地佐辛 β2肾上腺素受体/β-抑制蛋白2/核转录因子-κB 心肌细胞凋亡 

分 类 号：R614[医药卫生—麻醉学]