积雪草苷对异丙肾上腺素诱导小鼠心肌损伤的保护作用  

Protective effect of asiaticoside on isoproterenol induced myocardial injury in mice

作　　者：马子雨 左芯萌 王振宇 王明明 李翠 Ma Ziyu;Zuo Xinmeng;Wang Zhenyu;Wang Mingming;Li Cui(Dept of Physiology,School of Basic Medicine,Xuzhou Medical University,Xuzhou 221000;National Experimental Teaching Demonstration Center for Basic Medicine Xuzhou Medical University,Xuzhou 221000)

机构地区：[1]徐州医科大学基础医学院生理学教研室,徐州221000 [2]基础医学国家级实验教学示范中心(徐州医科大学),徐州221000

出　　处：《安徽医科大学学报》2025年第1期59-65,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81500177);江苏省自然科学基金(编号:BK20150211);江苏省研究生科研创新计划(编号:KYCX23_2942)。

摘　　要：目的探究积雪草苷(AS)对异丙肾上腺素(ISO)诱导小鼠心肌损伤的保护作用。方法将60只雄性C57BL/6小鼠随机分为空白对照(CON)组、模型[ISO,ISO 10 mg/(kg·d)]组、AS低剂量[ISO+AS-L,ISO 10 mg/(kg·d)+AS 5 mg/(kg·d)]组、中剂量[ISO+AS-M,ISO 10 mg/(kg·d)+AS 10 mg/(kg·d)]组、高剂量[ISO+AS-H,ISO 10 mg/(kg·d)+AS 20 mg/(kg·d)]组。统计心重比;观察心电图变化;酶联免疫吸附测定试验(ELISA)检测血清中白细胞介素(IL)-1β和心肌肌钙蛋白T(cTn-T)含量;Masson染色观察小鼠心肌组织纤维化情况;Western blot检测心肌组织中B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)蛋白表达量比值(Bax/Bcl-2)和半胱天冬酶-3(Caspase-3)、NOD样受体热蛋白结构域相关蛋白3(NLRP3)蛋白表达量;实时荧光定量聚合酶链式反应(qPCR)检测心房钠尿肽(ANP)、B型利钠肽(BNP)、β-肌球蛋白重链(β-MHC)、血清肿瘤坏死因子α(TNF-α)、IL-6、Ⅰ型胶原(COLⅠ)、Ⅲ型胶原(COLⅢ)mRNA表达水平。结果相较于CON组,ISO组心重比升高(P<0.01),心率降低(P<0.05),QT间期有所延长(P<0.05),心肌损伤标志物cTn-T、ANP、BNP和β-MHC表达升高(P<0.01);血清中IL-1β表达增加(P<0.01),心肌组织中TNF-α和IL-6表达增加(P<0.001),NLRP3蛋白表达量升高(P<0.05);心肌出现大量胶原纤维蓝染(P<0.001),且COLⅠ、COLⅢmRNA表达水平增加(P<0.001),Bax/Bcl-2比值(P<0.001)和Caspase-3表达量升高(P<0.05)。与ISO组比较,ISO+AS-L和ISO+AS-M组小鼠心重比降低(P<0.05),心率升高,QT间期有缩短趋势,cTn-T、ANP、BNP和β-MHC均降低(P<0.001),心肌胶原纤维蓝染减少(P<0.01),COLⅠ、COLⅢmRNA表达水平降低(P<0.05);IL-1β、TNF-α表达水平降低(P<0.01);NLRP3、Caspase-3蛋白表达量以及Bax/Bcl-2比值均降低(P<0.05);ISO+AS-M组IL-6表达水平降低(P<0.01);ISO+AS-H组ANP、BNP、TNF-αmRNA表达量表达水平降低(P<0.001);心肌纤维化程度有所改善(P<0.05);COLⅠ、COLⅢmRNA表达水平降低(P<0.05)。结论AS通过改�Objective To study the protective effect of asiaticoside(AS)on Isoproterenol Hydrochloride(ISO)-induced myocardial injury in mice.Methods Sixty male C57BL/6 mice were randomly divided into blank control(CON)group,model group[ISO,ISO 10/(kg·d)],Low dose group[ISO+AS-L,ISO 10 mg/(kg·d)+AS 5 mg/(kg·d)],Medium dose group[ISO+AS-M,ISO 10 mg/(kg·d)+AS 10 mg/(kg·d)],High dose group[ISO+AS-H,ISO 10 mg/(kg·d)+AS 20 mg/(kg·d)].Heart mass ratio was counted;changes were observed in electrocardiogram;Enzyme linked immunosorbent assay(ELISA)was used to detect the levels of interleukin(IL)-1βand cardiac troponin T(cTn-T)in serum;Masson staining was used to observe the fibrosis of mouse myocardial tissue;Western blot was used to detect the ratio of Bax and Bcl-2 protein expression levels(Bax/Bcl-2)and the expression levels of Caspase-3 and NLRP3 proteins in myocardial tissue;real-time quantitative polymerase chain reaction(qPCR)was used to detect the mRNA expression levels of ANP,BNP,β-MHC,TNF-α,IL-6,TypeⅠcollagen(COLⅠ),and TypeⅢcollagen(COLⅢ).Results Compared with the CON group,the ISO group had an elevated heart-to-mass ratio(P<0.01),a lower heart rate(P<0.05),a prolonged QT interval(P<0.05),elevated expression of myocardial injury markers cTn-T,ANP,BNP,andβ-MHC(P<0.01);increased expression of IL-1βin the serum(P<0.01),increased expression of TNF-αin the cardiac tissue and increased IL-6 expression(P<0.001),and NLRP3 protein expression was elevated(P<0.05);myocardium showed a large number of collagen fibers bluish staining(P<0.001),COLⅠ,COLⅢmRNA expression levels increased(P<0.001),and Bax/Bcl-2 ratio(P<0.001)and Caspase-3 expression were significantly elevated(P<0.05).Compared with ISO group,heart-to-mass ratio of mice in ISO+AS-L and ISO+AS-M groups decreased(P<0.05),heart rate increased,QT interval was shortened,cTn-T,ANP,BNP andβ-MHC decreased(P<0.001),myocardial collagen fiber blue-staining decreased(P<0.01).The mRNA expression levels of COLⅠand COLⅢdecreased(P<0.05).The expression levels of

关 键 词：积雪草苷 异丙肾上腺素 心肌损伤 凋亡 炎症 纤维化 保护作用 

分 类 号：R587.2[医药卫生—内分泌]