摘要
目的探讨三碘甲状腺原氨酸(T3)预处理对心肌梗死后心脏的保护作用及其机制。方法随机将24只小鼠分为4组,分别为:假手术组、手术组、手术+T3组、手术+T3+磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)抑制剂LY294002组(手术+T3+LY294002组),每组6只。采用结扎左冠状动脉前降支方法诱导小鼠发生急性心肌梗死。术前3 d腹腔注射预处理,前两组给予生理盐水,第三组给予T3[2μg/(100 g·d)],第四组给予T3+LY294002[2 mg/(100 g·d)]。术后4周,采用心脏超声检测小鼠心功能;采用苏木精-伊红染色观察心肌组织病理变化;采用酶联免疫吸附法检测梗死边缘区组织中炎症因子白介素-6和肿瘤坏死因子(TNF)-α水平;并用蛋白免疫印迹法检测心肌组织中凋亡相关蛋白Cleaved caspase-3、Bax、Bcl-2及通路相关蛋白T/p-PI3K和T/p-AKT的表达变化。结果与假手术组相比,手术组左室射血分数(LVEF)、左室短轴缩短率(FS)和Bcl-2蛋白水平明显下降,左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、心重/体重和心肌组织中白介素-6、TNF-α、Bax、Cleaved caspase-3、p-PI3K和p-AKT水平明显升高(P<0.05),心肌结构受损严重伴炎性细胞浸润;与手术组相比,手术+T3组LVEF、FS、Bcl-2、p-PI3K和p-AKT蛋白水平升高,LVESD、LVEDD和心肌组织中白介素-6、TNF-α、Bax和Cleaved caspase-3蛋白水平下降(P<0.05),心肌结构受损程度减轻伴炎性细胞浸润减少;与手术+T3组相比,手术+T3+LY294002组LVEF、FS、Bcl-2、p-PI3K和p-AKT蛋白水平明显下降,LVESD、LVEDD和心肌组织中白介素-6、TNF-α、Bax和Cleaved caspase-3蛋白水平升高(P<0.05),心肌结构受损程度加重伴炎性细胞浸润增加。结论T3可通过PI3K/AKT信号通路发挥抗心肌纤维化、抗炎症损伤和抗凋亡作用以保护梗死后心肌。
Objective To explore the protective effect and mechanism of triiodothyronine(T3)pretreatment on the heart after myocardial infarction(MI).Methods To divide 24 mice into 4 groups randomly:Sham,MI,MI+T3 and MI+T3+PI3K/AKT inhibitor LY294002(MI+T3+LY294002)group,and 6 animals in each group.Acute MI was induced by ligating the left anterior descending coronary artery in mice.Pretreatment was injected intraperitoneally three days before operation.The first two groups were given normal saline,the third group was given T3[2μg/(100 g·d)],and the fourth group was given T3+LY294002[2 mg/(100 g·d)].Cardiac ultrasound was used to detect cardiac function in mice four weeks after operation,H&E staining method was used to observe the pathological changes of myocardial tissue,ELISA was used to detect the level of inflammatory factors IL-6 and TNF-αin the tissue around the infarct border,and Western blotting was used to detect the expression changes of apoptosis-related proteins Cleaved caspase-3,Bax,Bcl-2 and pathway-related proteins T/p-PI3K and T/p-AKT in myocardial tissue.Results Compared with the Sham group,the left ventricular ejection fraction(LVEF),fractional shortening(FS),Bcl-2 protein level in the MI group decreased significantly,the left ventricular end-systolic dimension(LVESD),left ventricular end-diastolic dimension(LVEDD),heart/body weight ratio,and IL-6,TNF-α,Bax,Cleaved caspase-3,p-PI3K,p-AKT levels in myocardial tissue increased significantly(P<0.05),and myocardial structure was severely damaged with inflammatory cell infiltration.Compared with MI group,LVEF,FS,the protein levels of Bcl-2,p-PI3K and p-AKT increased in the MI+T3 group.LVESD,LVEDD,IL-6 and TNF-αin myocardial tissue and the protein levels of Bax and Cleaved caspase-3 were decreased(P<0.05).The degree of myocardial structural damage was reduced with reduced inflammatory cell infiltration.Compared with the MI+T3 group,LVEF,FS,protein levels of Bcl-2,p-PI3K and p-AKT in the MI+T3+LY294002 group decreased significantly,and LVESD,LVEDD,IL-6 and T
作者
张彩霞
曾彬
廖小婷
ZHANG Caixia;ZENG Bin;LIAO Xiaoting(Department of Cardiology,Renmin Hospital of Wuhan University,Cardiovascular Research Institute of Wuhan University,Hubei Key Laboratory of Cardiology,Wuhan 430060,Hubei,China)
出处
《心血管病学进展》
CAS
2020年第11期1209-1214,共6页
Advances in Cardiovascular Diseases
基金
国家自然科学基金青年基金(30900609)
国家自然科学基金(81270271,81570333)
中央高校基本科研业务费专项资金(2042020kf1014)。
