|本期目录/Table of Contents|

[1]王书飞,刘蕾,杜林翔,等.阿卡地新对冠心病大鼠AMPK/FOXO1信号通路及心功能损害的影响[J].天津医科大学学报,2021,27(05):496-501.
　WANG Shu-fei,LIU Lei,DU Lin-xiang,et al.Effects of acadesine on AMPK/FOXO1 signaling pathway and cardiac function damage in rats with coronary heart disease[J].Journal of Tianjin Medical University,2021,27(05):496-501.
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阿卡地新对冠心病大鼠AMPK/FOXO1信号通路及心功能损害的影响(PDF)
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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
27卷
期数:
2021年05期
页码:
496-501
栏目:
基础医学
出版日期:
2021-09-10

文章信息/Info

Title:
Effects of acadesine on AMPK/FOXO1 signaling pathway and cardiac function damage in rats with coronary heart disease
文章编号:
1006-8147(2021)05-0496-06
作者:
王书飞1; 刘蕾1; 杜林翔1; 张培培1; 左艳芳1; 逯党辉2
（1.河南省周口市中心医院心脏及内科重症监护室，周口 466000；2.河南省人民医院血管外科，郑州 450000）
Author(s):
WANG Shu-fei1; LIU Lei1; DU Lin-xiang1; ZHANG Pei-pei1; ZUO Yan-fang1; LU Dang-hui2
（1.CCU，Zhoukou Central Hospital of Henan Province，Zhoukou 466000，China；2. Department of Vascular Surgery，Henan Provincial People′s Hospital，Zhengzhou 450000，China ）
关键词:
阿卡地新; 冠心病; 心肌损伤; 腺苷单磷酸激活蛋白激酶/转录因子叉头框转录因子O亚族1
Keywords:
acadesine; coronary heart disease; cardiac function damage; adenosine monophosphate protein kinase/forkhead box transcription factor O1
分类号:
R541.4
DOI:
-
文献标志码:
A
摘要:
目的：探究阿卡地新对冠心病大鼠AMP活化蛋白激酶（AMPK）/转录因子叉头框转录因子O亚族1（FOXO1）信号通路及心功能损害的影响。方法：将72只Sprauge-Dawley（SD）大鼠采用随机数字表法分为正常组、模型组、地尔硫卓组（1.0 mg/kg）、阿卡地新高、中、低剂量组（2.0、1.0、0.5 mg/kg），每组12只。采用高脂饲料喂养+腹腔注射垂体后叶素法建立冠心病模型。造模后腹腔注射相应剂量的药物，正常组和模型组大鼠腹腔注射等量生理盐水，1次/d，连续注射14 d。采用超高分辨率小动物超声影像系统测量大鼠左心室收缩末期内径（LVESD）、左心室舒张末期内径（LVEDD）、射血分数（EF），短轴缩短率（FS）；检测血清炎症因子肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、肌酸激酶（CK）、肌酸激酶同工酶-MB（CK-MB），脂代谢指标甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白-胆固醇（LDL-C）水平以及心肌组织匀浆中超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）水平；HE染色观察心脏组织形态变化；Western印迹法检测心肌组织AMPK和FOXO1及其磷酸化蛋白的表达。结果：与正常组相比，模型组大鼠心肌组织染色不均，细胞水肿变性，伴有大量炎性细胞浸润，LVESD、LVEDD、血清CK、CK-MB、TNF-α、IL-6、TC、TG、LDL-C、心肌组织MDA水平、p-FOXO1表达升高（F=17.157～424.519，均P＜0.05），EF、FS、SOD、CAT、p-AMPK/AMPK、FOXO1表达下降（F=14.774～129.547，均P＜0.05）；与模型组相比，地尔硫卓组和阿卡地新高、中剂量组大鼠心肌细胞损伤减轻，LVESD、LVEDD、血清CK、CK-MB、TNF-α、IL-6、TC、TG、LDL-C、MDA、p-FOXO1表达降低（F=17.157～424.519，均P＜0.05），EF、FS、SOD、CAT、p-AMPK/AMPK、FOXO1表达升高（F=17.157～129.547，均P＜0.05）。结论：阿卡地新可能通过激活AMPK/FOXO1信号通路，减轻冠心病大鼠心功能损害。
Abstract:
Objective：To investigate the effect of acadesine on adenosine monophosphate protein kinase（AMPK）/forkhead box transcription factor O1（FOXO1）signaling pathway and cardiac function damage in rat with coronary heart disease. Methods: A total of 72 Sprauge-Dawley（SD）rats were randomly divided into normal group，model group，diltiazem group（1.0 mg/kg），acadesine high，middle，low dose groups （2.0，1.0，0.5 mg/kg） by random number table method，with 12 rats in each group. The model of coronary heart disease was established by feeding with high-fat diet and intraperitoneal injection of pituitrin. After modeling，the corresponding dose of drugs was injected intraperitoneally，the rats in the normal group and model group were intraperitoneally injected with the same amount of normal saline，once a day for 14 days. Left ventricular end systolic diameter（LVESD），left ventricular end diastolic diameter （LVEDD），ejection fraction （EF） and fractional shortening （FS） were measured by ultra-high resolution small animal ultrasound imaging system. The levels of serum inflammatory factors tumor necrosis factor-α （TNF-α），interleukin 6（IL-6），creatine kinase（CK），creatine kinase isoenzyme MB（CK-MB），lipid metabolism index triglyceride（TG），cholesterol（TC），low-density lipoprotein cholesterol（LDL-C） and superoxide dismutase（SOD），malondialdehyde（MDA），catalase（CAT） in myocardial tissue homogenate were measured. HE staining was used to observe the morphological changes of heart tissue，the expression of AMPK，FOXO1 and their phosphorylated proteins were detected by Western blotting B. Results：Compared with those in the normal group，the myocardial tissue in the model group was stained unevenly，with edema and degeneration，accompanied by a large number of inflammatory cells infiltration. In the model group，LVESD，LVEDD，levels of CK，CK-MB，TNF-α，IL-6，TC，TG and LDL-C in serum，level of MDA in myocardial tissue and expression of p-FOXO1 were increased（F=17.157-424.519，P＜0.05），EF，FS，the levels of SOD and CAT，the expression of p-AMPK/AMPK and FOXO1 were decreased（F=14.774-129.547，P＜0.05）.Compared with those in the model group，the myocardial cell injury was reduced in the diltiazem group，acadesine high and middle dose group，LVESD，LVEDD，levels of CK，CK-MB，TNF-α，IL-6，TC，TG and LDL-C in serum，level of MDA in myocardial tissue and expression of p-FOXO1 were decreased （F=17.157-424.519，P＜0.05），the EF，FS，the levels of SOD and CAT，the expression of p-AMPK/AMPK and FOXO1 were higher （F=17.157-129.547，P＜0.05）. Conclusion: Acadesine may reduce the damage of cardiac function in rats with coronary heart disease by activating AMPK/FOXO1 signaling pathway.

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备注/Memo

备注/Memo:
作者简介 王书飞(1987-)，男，主治医师，硕士，研究方向：心血管内科；通信作者：王娜，E-mail：leyan_2002@163.com。
更新日期/Last Update: 2021-09-01