OPG/RANKL/RANK在慢性心力衰竭大鼠心肌中的表达特征及其与心肌纤维化的关系  

Expression characteristics of OPG/RANKL/RANK and the relationshipwith fibrosis in myocardial tissues of rats with chronic heart failure

作　　者：杨薪 蔡学坤[1] 吴泽龙[1] 陈安涛 陈子豪 谢轩 区嘉康 黄兆琦[2] YANG Xin;CAI Xue-kun;WU Ze-long;CHEN An-tao;CHEN Zi-hao;XIE Xuan;OU Jia-kang;HUANG Zhao-qi(DepartmenttofGeriatrics,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,Guangdong Province,China;Department of Cardiology,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,Guangdong Province,China;Department of Clinical Medicine,Guangdong Medical University,Guangzhou 511495,Guangdong Province,China)

机构地区：[1]广州医科大学附属第三医院老年医学科,广东广州510150 [2]广州医科大学附属第三医院心血管内科,广东广州510150 [3]广州医科大学临床医学系,广东广州511495

出　　处：《中国临床药理学杂志》2025年第1期71-75,共5页The Chinese Journal of Clinical Pharmacology

基　　金：广东省医学科学技术研究基金资助项目(A2020174)。

摘　　要：目的研究骨保护素(OPG)/核因子κB受体活化因子配体(RANKL)/核因子κB受体活化因子(RANK)在慢性心力衰竭大鼠心肌中的表达特点,及其与心肌纤维化的关系。方法将SD大鼠随机分成假手术组(12只)和模型组。假手术组开腹后仅将手术丝线穿过腹主动脉,不缩窄腹主动脉;模型组用腹主动脉缩窄法复制慢性心力衰竭模型,并将造模成功的大鼠根据不同的观察时间随机分为模型1、2、4、8、12周组,分别有12、11、11、11、11只。实验终点为12周。比较各组大鼠心肌细胞中羟脯氨酸(HYP)、心肌胶原总含量及胶原容积分数(CVF),用蛋白质印迹法检测心肌细胞中OPG、RANKL和RANK蛋白的表达水平。结果假手术组和模型1、2、4、8、12周组心肌细胞中HYP含量分别为(0.25±0.04)、(0.37±0.05)、(0.45±0.04)、(0.60±0.05)、(0.82±0.10)和(1.03±0.07)μg·mg-1,心肌胶原总含量分别为(1.87±0.31)、(2.73±0.38)、(3.36±0.31)、(4.47±0.37)、(6.08±0.74)和(7.67±0.49)μg·mg-1,CVF分别为(1.95±0.23)%、(2.40±0.25)%、(3.65±0.25)%、(5.43±0.29)%、(6.97±0.36)%和(9.38±0.49)%,OPG蛋白相对表达水平分别为0.64±0.07、0.80±0.07、1.02±0.07、1.32±0.11、2.13±0.12和2.84±0.16,RANKL蛋白相对表达水平分别为0.71±0.08、1.06±0.07、1.53±0.07、2.62±0.12、4.46±0.14和6.11±0.16,RANK蛋白相对表达水平分别为0.30±0.05、0.45±0.05、0.63±0.06、0.98±0.07、1.43±0.10和1.63±0.10。随着时间的延长,模型组与假手术组相比,上述指标均显著升高,在统计学上差异均有统计学意义(均P<0.05)。慢性心力衰竭大鼠心肌细胞中OPG、RANK、RANKL蛋白相对表达水平与CVF、心肌胶原总含量均呈显著正相关(均P<0.01)。结论在慢性心力衰竭过程中,OPG/RANKL/RANK轴表达明显增强,其中以RANKL增强最为明显,且OPG/RANKL/RANK表达水平与CVF、心肌胶原总含量均呈显著正相关。Objective To study the expression characteristics of osteoprotegerin(OPG)/receptor activator of nuclear factor-κB ligand(RANKL)/receptor activator of nuclear factor-κB(RANK)system and the relationship with fibrosis in myocardial tissues of rats with chronic heart failure.Methods SD rats were randomly divided into sham-operation group(12 rats)and model group.In sham-operation group,surgical threadwas passed through the abdominal laorta without constricting it after laparotomy;in model group,establish the heart failure model by abdominal aorta coarctation.The successful model rats were randomly divided into model 1 week(12 rats),model 2 weeks(11 rats),model 4 weeks(11 rats),model 8 weeks(11 rats)and model 12 weeks groups(11 rats).The end point of the study is at week 12.The contents of hydroxyproline(HYP),total myocardial collagen and collagen volume fraction(CVF)were compaired in all proups.The expression levels of OPG,RANKL and RANK proteins in cardiomyocytes were determined by Western blot.Results The contents of HYP in sham-operation,model 1 week,model 2 weeks,model 4 weeks,model 8 weeks and model 12 weeks group were(0.25±0.04),(0.37±0.05),(0.45±0.04),(0.60±0.05),(0.82±0.10)and(1.03±0.07)μg·mg^(-1);the total myocardial collagen contents were(1.87±0.31),(2.73±0.38),(3.36±0.31),(4.47±0.37),(6.08±0.74)and(7.67±0.49)μg·mg^(-1);the CVF were(1.95±0.23)%,(2.40±0.25)%,(3.65±0.25)%,(5.43±0.29)%,(6.97±0.36)% and(9.38±0.49)%;the relative expression levels of 0PG protein were 0.64±0.07,0.80±0.07,1.02±0.07,1.32±0.11,2.13±0.12 and 2.84±0.16;the relative expression levels of RANKL protein were 0.71±0.08,1.06±0.07,1.53±0.07,2.62±0.12,4.46±0.14 and 6.11±0.16;the relative expression levels of RANK protein were 0.30±0.05,0.45±0.05,0.63±0.06,0.98±0.07,1.43±0.10 and 1.63±0.10.With the extention of time,the above indexs of all model groups were significantly higher than those in the sham-operation group(all P<0.05).There were positive linear correlation between the relative expression levels

关 键 词：心力衰竭 骨保护素 核因子ΚB受体活化因子配体 核因子ΚB受体活化因子 心肌纤维化 

分 类 号：R977.15[医药卫生—药品]