秋水仙碱通过调控Bcl-2/Cleaved-caspase3细胞凋亡途径改善异丙肾上腺素所致小鼠心肌损伤  

Colchicine attenuates isoproterenol-induced myocardial injury in mice via regulating the Bcl-2/Cleaved-caspase3 apoptosis signaling pathway

作　　者：董兰 丁瑞雪 唐文静 李叶丽 李意奇 杨丹莉 Dong Lan;Ding Ruixue;Tang Wenjing;Li Yeli;Li Yiqi;Yang Danli(Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education,Zunyi Medical University,Zunyi Guizhou 563099,China;School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563099,China)

机构地区：[1]遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563099 [2]遵义医科大学药学院,贵州遵义563099

出　　处：《遵义医科大学学报》2022年第4期427-432,共6页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:81660679)。

摘　　要：目的研究秋水仙碱(Col)对异丙肾上腺素(ISO)所致小鼠心肌损伤和心肌细胞凋亡的干预作用,并初步探讨其机制。方法18只雄性C57BL/6小鼠随机分为对照组、ISO组、Col组。ISO组和Col组经颈背部每天皮下注射ISO(5 mg/kg)1次,连续14 d,建立心肌损伤模型,对照组经颈背部皮下注射等体积生理盐水。同时,Col组每天灌胃给予Col(1 mg/kg)1次,对照组和ISO组每天灌胃给予等体积双蒸水。14 d后,称取动物心脏质量及体重,计算心脏质量指数(HMI);采用苏木精-伊红(H&E)染色检测小鼠左心室组织病理变化;Tunnel染色检测小鼠左心室组织心肌细胞凋亡情况;Western blot法检测小鼠左心室组织中的cTn I、Bcl-2、Cleaved-caspase3蛋白的表达。结果与Control相比,ISO组HMI升高(P<0.05);与ISO组相比,Col组HMI下降(P<0.05)。H&E染色结果显示Col能够改善ISO所致小鼠心肌细胞肥大、排列紊乱,并减轻左心室的炎性浸润;Tunnel染色结果显示Col能够减轻ISO所致小鼠左心室心肌细胞凋亡;Western blot结果显示Col能够对抗ISO所致小鼠左心室组织中Bcl-2表达的减少(P<0.05),并抑制小鼠左心室组织中cTn I、Cleaved-caspase3表达的升高(P<0.05)。结论Col能够改善ISO所致心肌损伤,其机制至少与其上调Bcl-2蛋白的表达、抑制Cleaved-caspase3的激活,减少心肌细胞凋亡相关。Objective To explore the effects of colchicine(Col)on cardiomyocyte apoptosis and myocardial injury induced by isoproterenol(ISO)in mice and further investigate its mechanisms.Methods Eighteen male C57BL/6 mice were randomly divided into control,ISO and ISO+Col groups.Mice were subcutaneously injected with ISO(5 mg/kg)on the back of the neck once a day for 14 days to establish the myocardial injury model,while control group were injected with the equal volume of normal saline.Meanwhile,Col group were intragastrically administrated of Col(1 mg/kg)once a day,Control group and ISO group were given the match volume of double distilled water.After 14 days,the heart and body weight were measured and the heart mass index(HMI)was calculated.The morphologic changes of the left ventricle were observed by hematoxylin-eosin(H&E)staining.The myocardial apoptosis of the left ventricle was observed by Tunnel staining.Western blot was used to detect the protein expressions of cTn I,Bcl-2 and Cleaved-caspase3 in the left ventricle.Results HMI was increased in the ISO group compared to that in Col group.HMI was decreased in the Col group compared to that in ISO group.H&E staining showed that Col improved the myocardial disorder and hypertrophy,and reduced the inflammatory infiltration of left ventricle induced by ISO in mice.Tunnel staining showed that Col reduced the myocardial apoptosis of left ventricle.Western blot demonstrated that Col counteracted the decreased-protein level of Bcl-2 and inhibited the increased-protein levels of cTn I,and Cleaved-caspase3 in the left ventricle induced by ISO in mice.Conclusion Col attenuates myocardial injury induced by ISO in mice,the mechanismis at least related to the up-regulation of the protein level of Bcl-2,inhibition of Cleaved-caspase3 and reduction of myocardial apoptosis.

关 键 词：秋水仙碱 心肌细胞凋亡 异丙肾上腺素 BCL-2 Cleaved-caspase3 

分 类 号：R966[医药卫生—药理学]