摘要
目的:观察姜黄素经内质网应激对缺血再灌注损伤大鼠心肌细胞凋亡的保护作用,为姜黄素的临床应用奠定实验基础。方法:50只雄性SD大鼠适应性饲养1周,随机分为5组:假手术组(sham组)、I/R组、Cur-L组[10 mg·(kg·d)^(-1)]、Cur-M组[20 mg·(kg·d)^(-1)]、Cur-H组[30 mg·(kg·d)^(-1)]。假手术组和I/R组给予生理盐水10 mg·(kg·d)^(-1),Cur-L组、Cur-M组、Cur-H组给予10 mg·(kg·d)^(-1)、20 mg·(kg·d)^(-1)、30 mg·(kg·d)^(-1)姜黄素,每日1次,给药15 d,在21 d后构建I/R模型,TUNEL染色观察心肌细胞凋亡程度,ELISA试剂盒检测血清CK-MB水平,RT-PCR检测心肌GRP78、Caspase-12、CHOP mRNA表达水平,免疫组化法检测心肌GRP78、Caspase-12、CHOP蛋白表达水平。结果:与sham组比较,I/R组及Cur-L组、Cur-M组、Cur-H组可见明显的凋亡细胞,凋亡指数增加(P<0.01);与I/R组比较,Cur-L组、Cur-M组、Cur-H组凋亡细胞减少,凋亡指数降低(P<0.01),其中,Cur-H组的凋亡指数最小(P<0.01)。与sham组比较,I/R组及Cur-L组、Cur-M组、Cur-H组大鼠血清中CK-MB显著升高(P<0.001);与I/R组比较,Cur-L组、Cur-M组、Cur-H组大鼠血清中CK-MB显著降低(P<0.001);与Cur-L组比较,Cur-M组、Cur-H组血清CK-MB显著降低(P<0.001);与sham组比较,I/R组及Cur-L组、Cur-M组、Cur-H组GRP78、CHOP、Caspase-12 mRNA及蛋白表达增加(P<0.05);与I/R组比较,Cur-L组、Cur-M组、Cur-H组GRP78 mRNA及蛋白表达增加,CHOP、Caspase-12 mRNA及蛋白表达降低(P<0.05);与Cur-L组比较,Cur-M组CHOP mRNA及蛋白表达增加,CHOP、Caspase-12 mRNA及蛋白表达降低(P<0.05)。结论:姜黄素通过增加心肌细胞中GRP78蛋白表达,抑制CHOP、Caspase-12蛋白表达改善心肌细胞凋亡。
Objective:To observe the protective effect of curcumin on myocardial cell apoptosis in rats with ischemiareperfusion injury through endoplasmic reticulum stress to provide the experimental foundation basis for the clinical application and treatment of curcumin.Methods:A total of 50 male SD rats were adaptively reared for 1 week.They were randomly divided into 5 groups:sham operation group,I/R group,Cur-L group[10 mg·(kg·d)^(-1)],Cur-M group[20 mg·(kg·d)^(-1)],Cur-H group[30 mg·(kg·d)^(-1)],the corresponding drugs were given once a day for 15 days.The I/R model was constructed after 21 days,TUNEL staining was used to observe the apoptosis of cardiomyocytes,and serum CK-MB was detected,immunohistochemical method was used to detect myocardial GRP78,Caspase-12,CHOP protein expression,RT-PCR to detect myocardial GRP78,Caspase-12,CHOP mRNA expression.Results:Compared with the sham operation group,the myocardial apoptosis index of the rats in the model group was significantly increased(P<0.01),and the pretreatment groups with different concentrations of curcumin could significantly improve the degree of myocardial cell apoptosis compared with the I/R group(P<0.01).Among them,the Cur-H group improved myocardial cell apoptosis.Apoptosis was the most obvious(P<0.01);compared with the sham operation group,the serum CK-MB of the rats in the model group was significantly increased(P<0.001),and compared with the I/R group,the serum CK-MB of the rats in the different concentrations of curcumin pretreatment group was significantly decreased(P<0.001).Compared with Cur-L group,the CK-MB of Cur-M group and Cur-H group was significantly decreased(P<0.001).Compared with the I/R group,the expression of GRP78 mRNA and GRP78 protein in the curcumin group with different concentrations increased(P<0.05),while CHOP mRNA,Caspase-12 mRNA,CHOP,Caspase-12 protein expression decreased(P<0.05).Compared with Cur-L group,CHOP mRNA expession and protein expression of Cur-M group increased,and CHOP,Caspase-12 mRNA\and protein expression decrea
作者
曾石秀
陈艳
韩巧秀
刘贱丰
王丽
钟一鸣
ZENG Shi-xiu;CHEN Yan;HAN Qiao-xiu;LIU Jian-feng;WANG Li;ZHONG Yi-ming(Cardiology Department,The First Affiliated Hospital of Gannan Medical University;The Second Section of Internal Medicine,Huichang Hospital of Traditional Chinese Medicine;Department of Pathology,The First Affiliated Hospital of Gannan Medical University;Clinical Laboratory,The First Affiliated Hospital of Gannan Medical University;Information Centre,The First Affiliated Hospital of Gannan Medical University,Ganzhou,Jiangxi 341000)
出处
《赣南医学院学报》
2023年第9期943-949,共7页
JOURNAL OF GANNAN MEDICAL UNIVERSITY
基金
江西省卫生健康委员会科技计划项目(202130637)
江西省2020年度03专项及5G项目(20204ABC03A31)。
关键词
姜黄素
内质网应激
缺血再灌注损伤
凋亡
Curcumin
Endoplasmic reticulum stress
Myocardial ischemia/reperfusion injury
Apoptosis
