二氧化硫对大鼠急性心肌缺血损伤后心肌纤维化的改善作用及其机制  

Improvement effect of SO2 on myocardial fibrosis after acute myocardial ischemic injury in rats and its mechanism

作　　者：刘星 刘佳丽 聂连桂 刘茂军 赵俊雄 汪刘洋 杨军 LIU Xing;LIU Jiali;NIE Liangui;LIU Maojun;ZHAO Junxiong;WANG Liuyang;YANG Jun(Department of Cardiology,First Affiliated Hospital,Hengyang Medical College,University of South China,Hengyang 421001,China)

机构地区：[1]南华大学衡阳医学院附属第一医院心内科,湖南衡阳421001

出　　处：《吉林大学学报（医学版）》2023年第5期1125-1133,共9页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助项目(81870230);湖南省科技厅自然科学基金青年基金项目(2021JJ40499,2020JJ5505)。

摘　　要：目的:观察二氧化硫(SO_(2))对大鼠急性心肌缺血损伤后心肌纤维化(MF)的影响,并探讨其作用机制。方法:24只雄性SD大鼠随机分为对照组(不处理)、异丙肾上腺素(ISO)组(给予ISO)、ISO+SO_(2)组(给予ISO+SO_(2))和SO_(2)组(给予SO_(2)),每组6只。ISO组和ISO+SO_(2)组大鼠连续2 d腹腔注射大剂量ISO(50 mg·kg^(-1)·d^(-1))构建急性心肌缺血损伤模型。造模成功后,ISO+SO_(2)组和SO_(2)组大鼠给予Na2SO3溶液(0.54 mmol·kg^(-1)·d^(-1))和NaHSO3溶液(0.18 mmol·kg^(-1)·d^(-1)),连续4周,对照组和ISO组大鼠给予等量生理盐水。检测4组大鼠血浆肌钙蛋白水平和心电图,超声心动图检测4组大鼠左室短轴缩短率(LVFS)和左室射血分数(LVEF),Masson染色检测4组大鼠心肌组织中胶原沉积情况并计算胶原体积分数(CVF),Tunel染色检测4组大鼠心肌细胞凋亡率,Western blotting法检测4组大鼠心肌组织中自噬相关蛋白3 (Atg3)、自噬相关蛋白5 (Atg5)、自噬相关蛋白16L1 (Atg16L1)、含半胱氨酸的天冬氨酸蛋白水解酶3 (Caspase-3)、含半胱氨酸的天冬氨酸蛋白水解酶9 (Caspase-9)、基质金属蛋白酶8 (MMP-8)和金属蛋白酶组织抑制物2 (TIMP-2)蛋白表达水平。结果:与对照组比较,ISO组和ISO+SO_(2)组大鼠心电图ST段明显抬高,肌钙蛋白水平升高(P<0.05),提示急性心肌缺血损伤大鼠造模成功;与对照组比较,ISO组大鼠LVFS和LVEF降低(P<0.05),心肌组织中CVF升高(P<0.05),心肌细胞凋亡率升高(P<0.05),心肌组织中Atg3、Atg5、Atg16L1、Caspase-3、Caspase-9和MMP-8蛋白表达水平升高(P<0.05),TIMP-2蛋白表达水平降低(P<0.05);与ISO组比较,ISO+SO_(2)组大鼠LVFS和LVEF升高(P<0.05),心肌组织中CVF降低(P<0.05),心肌细胞凋亡率降低(P<0.05),心肌组织中Atg3、 Atg5、Atg16L1、Caspase-3、Caspase-9和MMP-8蛋白表达水平降低(P<0.05),TIMP-2蛋白表达水平升高(P<0.05)。结论:SO_(2)可以改善大鼠急性心肌缺血损伤后MF,其机制可能与抑制Objective:To observe the effect of sulfur dioxide(SO_(2))on the myocardial fibrosis(MF)after acute myocardial ischemic injury in the rats,and to explore its mechanism.Methods:Twenty-four male SD rats were randomly divided into control group(untreated),isoproterenol(ISO)group(treated with ISO),ISO+SO_(2) group(treated with ISO and SO_(2)),and SO_(2) group(treated with SO_(2)),and there were six rats in each group.The acute myocardial ischemic injury model rats in ISO group and ISO+SO_(2) group were induced by intraperitoneal injection with a high dose of ISO(50 mg·kg^(-1)·d^(-1))for 2 d.After successful modeling,the rats in ISO+SO_(2) group and SO_(2) group were treated with Na2SO3 solution(0.54 mmol·kg^(-1)·d^(-1))and NaHSO3 solution(0.18 mmol·kg^(-1)·d^(-1))for four weeks,while the rats in control group and ISO group were treated with equal volume of physiological saline intraperitoneally.The levels of myocardial troponin in plasma and electrocardiogram of the rats in various groups were detected;the left ventricular fractional shortening(LVFS)and left ventricular ejection fraction(LVEF)of the rats in various groups were detected by echocardiography;the collage deposition in myocadium tissue of the rats in various groups was detected by Masson staining and the collagen volume fraction(CVF)was calculated;the apoptotic rates of cardiomyocytes of the rats in various groups were detected by Tunel staining;the expression levels of autophagy-related proteins 3(Atg3),autophagy-related protein 5(Atg5),autophagyrelated protein 16L1(Atg16L1),aspartate proteolytic enzyme containing cysteine 3(Caspase-3),aspartate proteolytic enzyme containing cysteine 9(Caspase-9),matrix metalloproteinase 8(MMP-8),and tissue inhibitor of metalloproteinase 2(TIMP-2)proteins in myocardium tissue of the rats in various groups were detected by Western blotting method.Results:Compared with control group,the ST segment in electrocardiogram of the rats in ISO group and ISO+SO_(2) group showed elevation and the levels of myocardial troponin

关 键 词：二氧化硫 心肌缺血 心肌纤维化 细胞自噬 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]