鸢尾素在阿霉素心肌病中的保护作用和机制  

Protective role and mechanistic exploration of Irisin in doxorubicin induced-cardiomyopathy

作　　者：金宇鸽 李松森[2] 王皓 郭彩茹 张兵兵 陈浩杰 班亚鑫 梁如冰 JIN Yu-ge;LI Song-sen;WANG Hao;GUO Cai-ru;ZHANG Bing-bing;CHEN Hao-jie;BAN Ya-xin;LIANG Ru-bing(Graduate School,Xinxiang Medical University,Xinxiang 453003,Henan Province,China;Department of Cardiology,Luoyang Central Hospital,Luoyang 471000,Henan Province,China;Central Laboratory,Luoyang Central Hospital,Luoyang 471000,Henan Province,China;Graduate School,Zhengzhou University,Zhengzhou 450001,Henan Province,China)

机构地区：[1]新乡医学院研究生院,河南新乡453003 [2]洛阳市中心医院心内科,河南洛阳471000 [3]洛阳市中心医院中心实验室,河南洛阳471000 [4]郑州大学研究生院,河南郑州450001

出　　处：《中国临床药理学杂志》2024年第2期220-224,共5页The Chinese Journal of Clinical Pharmacology

基　　金：河南省重点研发与推广专项(科技攻关)基金资助项目(212102310810、222102310113);洛阳市公益性行业医疗卫生专项基金资助项目(2302038Y)。

摘　　要：目的研究鸢尾素(Irisin)对阿霉素(Dox)心肌病的保护作用,并研究其可能作用机制。方法用AC16细胞构建Dox损伤模型,并将其随机分为对照组(AC16细胞用完全培养基培养)、鸢尾素组(AC16细胞用10 ng·L^(-1)的鸢尾素处理24 h)、Dox组(用4μmol·L^(-1)Dox处理24 h)、Dox+鸢尾素组(AC16细胞用10 ng·L^(-1)的鸢尾素预处理2 h后,再加入4μmol·L^(-1)Dox处理24 h),用细胞计数试剂盒-8(CCK-8)、脱氧核苷酸末端转移介导的缺口末端标记法(TUNEL)和乳酸脱氢酶(LDH)检测其增殖、凋亡和死亡率,蛋白质印迹(West⁃ern blot)法检测细胞核因子-κB(NF-κB)信号通路和凋亡因子B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、半胱氨酸天冬氨酸特异性蛋白酶9(caspase-9)蛋白的表达水平,用Mito-Tracker Red CMXRos探针检测线粒体膜电位。结果对照组、鸢尾素组、Dox组、Dox+鸢尾素组的细胞凋亡率分别为(0.97±0.09)%、0、(42.80±6.70)%和(11.74±1.79)%,Bax的蛋白表达水平分别为0.85±0.01、0.36±0.02、1.15±0.07和0.37±0.11,caspase-9的蛋白表达水平分别为0.52±0.02、0.59±0.03、1.11±0.02和0.67±0.08,Bcl-2的蛋白表达水平分别为1.01±0.04、1.05±0.25、0.43±0.02、0.99±0.30,线粒体损伤概率分别为(0.02±0.01)%、(0.5±0.15)%、(38.6±2.39)%和(1.58±0.54)%。上述指标,Dox组与对照组比较,Dox+鸢尾素组与Dox组比较,在统计学上差异均有统计学意义(均P<0.05)。结论鸢尾素可降低Dox引起的Bax、caspase 9、p-NF-κB、p-mTOR的表达水平,升高Bcl-2的表达水平,改善阿霉素所致的心肌损伤,减轻心脏毒性。Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC16 cells were used to construct Dox injury model and divided into control group(AC16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L^(-1)Irisin for 24 h),Dox group(AC16 cells were treated with 4μmol·L^(-1)Dox for 24 h),Dox+Irisin group(AC16 cells were pretreated with 10 ng·L^(-1)Irisin for 2 h,and then treated with 4μmol·L^(-1)Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lym ph oma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)%,0,(42.80±6.70)%,(11.74±1.79)%;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)%,(0.5±0.15)%,(38.6±2.39)%,(1.58±0.54)%.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P<0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P<0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

关 键 词：鸢尾素 阿霉素 心肌损伤 细胞核因子-κB信号通路 

分 类 号：R28[医药卫生—中药学]