摘要
目的:比较羟考酮与吗啡对心肌缺血再灌注损伤(myocardial ischemia reperfusion injury,MIRI)时氧化应激的影响。方法:雄性SD大鼠80只,随机分组(每组16只):假手术组(S组)、MIRI组(I组)、羟考酮组(O组)、吗啡组(M组)、羟考酮+κ受体拮抗剂组(K组)。MIRI模型制作方法为结扎左冠状动脉前降支30 min,再灌注180 min。S组只穿线不结扎;O组和M组、K组分别于再灌注前5 min经尾静脉注射羟考酮0.5 mg·kg^(-1)、吗啡1.5 mg·kg^(-1)、羟考酮0.5 mg·kg^(-1)+κ受体拮抗剂0.5 mg·kg^(-1)。分别测定心肌梗死面积(ARI)、血清肌钙蛋白(cTnI)浓度、心肌组织学改变及Mn-SOD阳性细胞比例。结果:与S组比较,I组cTnI升高(P<0.05),ARI增大(P<0.05),心肌组织病理损伤重,Mn-SOD阳性细胞减少(P<0.05);与I组比较,O组和M组血清中cTnI降低(P<0.05),ARI减少(P<0.05),心肌组织病理损伤较轻,Mn-SOD阳性细胞升高(P<0.05);与O组比较,M组、K组血清中cTnI升高(P<0.05),ARI增大(P<0.05),心肌组织病理损伤较重,Mn-SOD阳性细胞减少(P<0.05)。结论:羟考酮可更显著抑制大鼠心肌缺血再灌注损伤时心肌氧化应激反应,减轻心肌缺血再灌注损伤,其机制可能与羟考酮与心肌细胞膜上κ受体结合来抑制心肌组织氧化应激反应有关。
OBJECTIVE To compare the effects of oxycodone and morphine on reducing oxidative stress during myocardial ischemia reperfusion injury(MIRI)in rat model.METHODS Eighty male SD rats were randomly divided into 5 groups with 16 ones in each group:sham operation group(group S),MIRI group(group I),oxycodone group(group O),morphine group(group M),and oxycodone+κreceptor antagonist(aticaprant)group(group K).The model of rat myocardial ischemia reperfusion injury was established by ligating left anterior descending coronary artery for 30 min and reperfusing for 180 min.In group S,thoracotomy was performed without left anterior descending coronary artery ligation.In groups O,M,K,after ligation of left anterior descending artery,oxycodone 0.5 mg·kg^(-1),morphine 1.5 mg·kg^(-1)and oxycodone 0.5 mg·kg^(-1)+κreceptor antagonist 0.5 mg·kg^(-1)were injected respectively through tail vein at 5 min before reperfusion,and reperfusion was lasted for 180 min.After successful modeling,rat’s heart was isolated,and then left ventricle was isolated.The area ratio of myocardial infarction(ARI)was determined by 2,3,5-triphenyltetrazolium chloride(TTC)staining;serum troponin(cTnI)concentration was measured by enzyme immunosorbent assay(ELISA)under UniCel DxI 800 laboratory automation system;HE staining was used to detect myocardial histological changes,and immunohistochemistry was used to detect the proportion of Mn-SOD positive cells.RESULTS Compared with that in group S,the level of cTnI and ARI in group I significantly increased(P<0.05),the pathological damage of myocardial tissue was severe,and the proportion of Mn-SOD positive cells was significantly reduced(P<0.05);compared with that in group I,the level of cTnI and ARI in group O and M was significantly reduced(P<0.05),the pathological damage of myocardial tissue was lighter,and the proportion of Mn-SOD positive cells significantly increased(P<0.05);compared with that in group O,the level of cTnI and ARI in groups M and K increased significantly(P<0.05),the pathological damag
作者
杨静
贾圣琪
汪煜
田丁元
申文增
贾辛未
YANG Jing;JIA Sheng-qi;WANG Yu;TIAN Ding-yuan;SHEN Wen-zeng;JIA Xin-wei(Department of Cardiology,Affiliated Hospital of Hebei University,Hebei Baoding 071000,China;Department of Cardiology(Ward 4),Second Hospital of Hebei Medical University,Hebei Shijiazhuang 050000,China;Institute of Endocrinology,Chu Hsien-I Memorial Hospital of Tianjin Medical University,Tianjin 300070,China;Functional Laboratory,College of Basic Medcine,Hebei University,Hebei Baoding 071000,China)
出处
《中国医院药学杂志》
CAS
北大核心
2022年第15期1528-1532,共5页
Chinese Journal of Hospital Pharmacy
基金
2021年度政府资助临床医学优秀人才培养项目(编号:冀卫办科教[2021]9号)。