[1]潘瑞洋,孙家珍,赵奕霖,等.辛伐他汀对慢性心力衰竭兔人第10号染色体缺失的磷酸酶及张力蛋白同源基因和β-catenin表达的影响[J].新乡医学院学报,2017,34(12):1048-1052.[doi:10.7683/xxyxyxb.2017.12.002]
　PAN Rui-yang,SUN Jia-zhen,ZHAO Yi-lin,et al.Effect of simvastatin on phosphatase and tensin homologue deleted on chromosome ten and β-catenin of rabbits with chronic heart failure[J].Journal of Xinxiang Medical University,2017,34(12):1048-1052.[doi:10.7683/xxyxyxb.2017.12.002]
点击复制

辛伐他汀对慢性心力衰竭兔人第10号染色体缺失的磷酸酶及张力蛋白同源基因和β-catenin表达的影响
分享到：

《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
34
期数:
2017年12
页码:
1048-1052
栏目:
基础研究
出版日期:
2017-12-05

文章信息/Info

Title:
Effect of simvastatin on phosphatase and tensin homologue deleted on chromosome ten and β-catenin of rabbits with chronic heart failure
作者:
潘瑞洋1; 孙家珍2; 赵奕霖1; 赵国安3
（1.新乡医学院第三附属医院心血管内科，河南　新乡　453003；2.新乡医学院第三附属医院生殖医学科，河南　新乡　453003；3.新乡医学院第一附属医院，河南　卫辉　453100）
Author(s):
PAN Rui-yang1; SUN Jia-zhen2; ZHAO Yi-lin1; ZHAO Guo-an3
（1.Department of Cardiology，the Third Affiliated Hospital of Xinxiang Medical University，Xinxiang 453003，Henan Province，China；2.Reproductive Medicine Center，the Third Affiliated Hospital of Xinxiang Medical University，Xinxiang 453003，Henan Province，China；3.The First Affiliated Hospital of Xinxiang Medical University，Weihui 453100，Henan Province，China）
关键词:
辛伐他汀; 慢性心力衰竭; 阿霉素; 人第10号染色体缺失的磷酸酶及张力蛋白同源基因; β-catenin
Keywords:
simvastatin; chronic heart failure; adriamycin; phosphatase and tensin homologue deleted on chromosome 10; β-catenin
分类号:
R541.6
DOI:
10.7683/xxyxyxb.2017.12.002
文献标志码:
A
摘要:
目的　探讨辛伐他汀对慢性心力衰竭兔心肌细胞中人第10号染色体缺失的磷酸酶及张力蛋白同源基因（PTEN）和β-catenin表达的影响。方法　将24只雄性新西兰大耳白兔随机分为对照组、心力衰竭模型组和辛伐他汀组，每组8只。心力衰竭模型组和辛伐他汀组兔经耳缘静脉注射盐酸阿霉素2.0 mg·kg-1，每周1次，连续6周，第7周起经耳缘静脉注射盐酸阿霉素1.5 mg·kg-1，连续6周，建立慢性心力衰竭兔模型；对照组兔给予等量的生理盐水。辛伐他汀组兔在首次注射盐酸阿霉素时给予辛伐他汀灌胃（1.5 mg·kg-1·d-1），连续12周；对照组和心力衰竭模型组兔给予等量生理盐水灌胃12周。造模结束后通过心脏超声测量兔左心室结构和功能。处死动物留取左心室室壁，苏木精-伊红染色观察心肌细胞结构，免疫组织化学染色检测心肌细胞中PTEN、β-catenin蛋白的表达，实时荧光定量聚合酶链反应检测PTEN、β-catenin mRNA的表达。结果　与对照组比较，心力衰竭模型组、辛伐他汀组兔的左心室收缩末期内径（LVESD）和左心室舒张末期内径（LVEDD）增大，左心室射血分数（LVEF）降低（P<0.05）；与心力衰竭模型组比较，辛伐他汀组兔的LVESD、LVEDD减小，LVEF升高（P<0.05）。对照组、心力衰竭模型组、辛伐他汀组兔心肌细胞PTEN蛋白阳性表达率分别为（16.36±0.54）%、（41.63±0.72）%、（24.17±0.51）%，对照组、心力衰竭模型组、辛伐他汀组兔心肌细胞β-catenin蛋白阳性表达率分别为（21.73±0.46）%、（52.26±0.72）%、（38.42±0.56）%；心力衰竭模型组和辛伐他汀组兔心肌细胞PTEN、β-catenin蛋白阳性表达率高于对照组（P<0.05），辛伐他汀组兔心肌细胞PTEN、β-catenin蛋白阳性表达率低于心力衰竭模型组（P<0.01）。对照组、心力衰竭模型组、辛伐他汀组兔心肌细胞中PTEN mRNA相对表达量分别为1.91±0.30、4.61±0.71、3.49±0.64，对照组、心力衰竭模型组、辛伐他汀组兔心肌细胞中β-catenin mRNA相对表达量分别为1.51±0.21、2.48±0.34、1.51±0.25；心力衰竭模型组和辛伐他汀组兔心肌细胞中PTEN、β-catenin mRNA相对表达量高于对照组（P<0.05），辛伐他汀组兔心肌细胞中PTEN、β-catenin mRNA相对表达量低于心力衰竭模型组（P<0.05）。结论　辛伐他汀可抑制慢性心力衰竭兔心肌凋亡，提高心功能，其机制可能与抑制PTEN、β-catenin表达有关。
Abstract:
Objective　To study the effect of simvastatin on the expression of phosphatase and tensin homologue deleted on chromosome 10（PTEN） and β-catenin in myocardial cells of rabbits with chronic heart failure(CHF).Methods　Twenty-four male New Zealand rabbits were randomly divided into control group，CHF model group and simvastatin treatment group，with 8 rabbits in each group.The rabbits in CHF model group and simvastatin treatment group were injected with adriamycin （2.0 mg·kg-1） ria ear rein once a week for six weeks，and from the seventh week were injected with adriamycin （1.5 mg·kg-1）once a week for another six weeks to establish the CHF model；the rabbits in control group were injected with the same volume saline.The rabbits in simvastatin treatment group were given simvastatin （1.5 mg·kg-1·d-1） by intragastric administration at the time point of first injection of adriamycin for 12 weeks；the rabbits in CHF model group and control group were given the same volume saline for 12 weeks.The left ventricular structure and function were determined by color doppler ultrasonography after the modeling.Then the rabbits were sacrificed and the left ventricular walls were taken to observe the changes of myocardial cell structures by hematoxylin-eosin staining.The positive expression rate of PTEN and β-catenin protein was calculated by immunohistochemistry staining.The expression of PTEN and β-catenin mRNA was detected real-time quantitative polymerase chain reaction.Results　Compared with the control group，the left ventricular end-systolic dimension（LVESD），left ventricular end-diastolic dimension（LVEDD） were increased and the left ventricular ejection fraction（LVEF） was decreased in the CHF model group and simvastatin treatment group（P<0.05）.Compared with the CHF model group，the LVESD，LVEDD were decreased and the LVEF was increased in the simvastatin treatment group（P<0.05）.The positive expression rate of PTEN protein in myocardial cells of rabbits in control group，CHF model group and simvastatin treatment group was （16.36±0.54）%，（41.63±0.72）% and （24.17±0.51）% respectively；the positive expression rate of β-catenin protein in myocardial cells of rabbits in control group，CHF model group and simvastatin treatment group was （21.73±0.46）%，（52.26±0.72）% and （38.42±0.56）% respectively.The positive expression rates of PTEN and β-catenin protein in myocardial cells of rabbits in CHF model group and simvastatin treatment group were significanlty higher than those in the control group（P<0.05）；the positive expression rates of PTEN and β-catenin protein of myocardial cell in simvastatin treatment group were significantly lower than those in the CHF model group （P<0.05）.The epression of PTEN mRNA and β-catenin mRNA in myocardial cells of rabbits in control group，CHF model group and simvastatin treatment group was 1.91±0.30，4.61±0.71，3.49±0.64 and 1.51±0.21，2.48±0.34，1.51±0.25.The expression of PTEN and β-catenin mRNA in myocardial cells of rabbits in CHF model group and simvastatin treatment group were significanlty higher than those in the control group（P<0.05）；the expression of PTEN and β-catenin mRNA in myocardial cells of rabbits in simvastatin treatment group were significantly lower than those in the CHF model group （P<0.05）.Conclusion　Simvastatin can inhibit myocardial apoptosis，improve cardiac function of CHF rabbits.It may be related to inhibiting the expression of PTEN and β-catenin.

参考文献/References:

［1］　TSAO L，GIBSON C M.Heart failure：an epidemic of the 21st century［J］.Crit Pathw Cardiol，2004，3（4）：194-204.
［2］　高艳辉，郑方方，孔一慧，等.解偶联蛋白2与心力衰竭的关系［J］.国际心血管病杂志，2013，40 （2）：101-102.
［3］　LIU P Y，LIU Y W，LIN L J，et al.Evidence for statin pleiotropy in humans：differential effects of statins and ezetimibe on rho-associated coiled-coil containing protein kinase activity，endothelial function，and inflammation［J］.Circulation，2009，119（1）：131-138.
［4］　TSUKAHARA S，YAMAMOTO S，SHWE T T W，et al.Inhalation of low-level formaldehyde increases the Bcl-2/Bax expression ratio in the hippocampus of immunologically sensitized mice［J］.Neuroimmunomodulation，2006，13（2）：63-68.
［5］　王晓垒，赵国安.慢性心力衰竭患者血浆脑钠肽、尿酸及高敏 C 反应蛋白水平与心肾功能的相关性［J］.新乡医学院学报，2017，34（8）：762-765，768.
［6］　DEO S H，FISHER J P，VIANNA L C，et al.Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure［J］.Am J Physiol Heart Circ Physiol，2012，303 （3）：H377-H385.
［7］　孙喜文，张灿.辛伐他汀对慢性心力衰竭患者血浆NT-pro BNP及心功能的影响研究［J］.实用心脑肺血管病杂志，2011，19（6）：937-938.
［8］　WANG L，SHI J，ZHANG Y.Influences of simvastatin on vascular endothelial function of patients with coronary heart disease complicated with congestive heart failure［J］.Eur Rev Med Pharmacol Sci，2013，17（12）：1590-1593.
［9］　LAUFS U，CUSTODIS F，BOHM M.HMG-CoA reductase inhibitors in chronic heart failure［J］.Drugs，2006，66：145-154.
［10］　ALESSIO N，BOHN W，RAUCHBERGER V，et al.Silencing of RB1 but not of RB2/P130 induces cellular senescence and impairs the differentiation potential of human mesenchymal stem cells［J］.Cell Mol Life Sci，2013，70（9）：1637-1651.
［11］　杨永健，朱文玲，张鑫，等.PTEN/磷脂酰肌醇3激酶通路在心力衰竭患者心肌重构中的信号传导作用［J］.中华医学杂志，2005，85（17）：1201-1204.
［12］　KEYES K T，XU J，LONG B，et al.Pharmacological inhibition of PTEN limits myocardial infarct size and improves left ventricular function postinfarction［J］.Am J Physiol Heart Circ Physiol，2010，298（4）：H1198-H1208.
［13］　PARAJULI N，YUAN Y，ZHENG X，et al.Phosphatase PTEN is critically involved in post-myocardial infarction remodeling through the Akt/interleukin-10 signaling pathway［J］.Basic Res Cardiol，2012，107（2）：1-15.
［14］　牛潼，刘琦然，李玲.Wnt/β-catenin信号通路对肾小管上皮间充质转分化的调控［J］.中华实用儿科临床杂志，2016，31（12）：958-960.
［15］　黄华艺，农朝赞，查锡良.新癌基因β-catenin研究进展［J］.中华消化杂志，2002，22（8）：497-498.
［16］　阮滔，何学华，刘丽萍，等.Wnt2、β-catenin在多柔比星诱导心肌损伤中的表达及其与p53的关系［J］.中华实用儿科临床杂志，2015，30（5）：370-373.
［17］　张俊芳，管怀进，张金迪，等.β-连接蛋白在DBA/2J小鼠视网膜的表达［J］.眼科新进展，2013，33 （9）：808-811.
［18］　SCHUMANN H，HOLTZ J，ZERKOWSKI H R，et al.Expression of secreted frizzled related proteins 3 and 4 in human ventricular myocardium correlates with apoptosis related gene expression［J］.Cardiovasc Res，2000，45（3）：720-728.
［19］　张友明，朱红涛.WNT信号通路与心血管疾病的研究进展［J］.国际心血管病杂志，2016，43（5）：269-272.
［20］　沈鑫，马依彤，杨毅宁，等.FrzA 基因转导干预缺血性心力衰竭小鼠心肌WNT信号通路的研究［J］.中国生物工程杂志，2013，33（7）：13-17.

相似文献/References:

[1]刘阳责,李维国,凌 云· 王明焱,等.倍他乐克对慢性心力衰竭的治疗价值[J].新乡医学院学报,2000,17(02):095.
[2]韩 曼,马 莉,于远望.2种慢性心力衰竭大鼠模型的建立[J].新乡医学院学报,2015,32(11):992.
[3]董　征,周雯雯.慢性心力衰竭患者心脏同步化治疗效果与肺动脉收缩压的关系[J].新乡医学院学报,2016,33(10):887.[doi:10.7683/xxyxyxb.2016.10.013]
　DONG Zheng,ZHOU Wen-wen.Relationship between the effect of cardiac resynchronization therapy and pulmonary artery systolic pressure in patients with chronic heart failure[J].Journal of Xinxiang Medical University,2016,33(12):887.[doi:10.7683/xxyxyxb.2016.10.013]
[4]张全英,孙俊俊,张朝辉,等.情绪体验在慢性心力衰竭患者主要照顾者精力与照顾者负担间的中介作用[J].新乡医学院学报,2021,38(5):422.[doi:10.7683/xxyxyxb.2021.05.005]
　ZHANG Quanying,SUN Junjun,ZHANG Zhaohui,et al.Mediating role of emotion between energy and burden in major caregivers of chronic heart failure patients[J].Journal of Xinxiang Medical University,2021,38(12):422.[doi:10.7683/xxyxyxb.2021.05.005]
[5]韩亚军,张荣怀,王晓明.左西孟旦注射液和托拉塞米注射液联合治疗老年慢性心力衰竭疗效观察[J].新乡医学院学报,2021,38(1):057.[doi:10.7683/xxyxyxb.2021.01.012]
　HAN Yajun,ZHANG Ronghuai,WANG Xiaoming.Curative effect of levosimendan injection combined with torasemide injection in the treatment of elderly patients with chronic heart failure[J].Journal of Xinxiang Medical University,2021,38(12):057.[doi:10.7683/xxyxyxb.2021.01.012]
[6]周翠翠,吕风华,王现伟.血清同型半胱氨酸和胱抑素C对慢性心力衰竭患者早期肾损伤的诊断价值[J].新乡医学院学报,2021,38(11):1025.[doi:10.7683/xxyxyxb.2021.11.005]
　ZHOU Cuicui,LYU Fenghua,WANG Xianwei.Clinical value of serum homocysteine and cystatin C in the diagnosis of early renal injury in patients with chronic heart failure[J].Journal of Xinxiang Medical University,2021,38(12):1025.[doi:10.7683/xxyxyxb.2021.11.005]
[7]彭　敏,闫　超.瑞舒伐他汀钙对老年慢性心力衰竭患者氧化-抗氧化系统及血管内皮细胞功能的影响[J].新乡医学院学报,2017,34(8):751.[doi:10.7683/xxyxyxb.2017.08.024]
　PENG Min,YAN Chao.Effects of rosuvastatin calcium on oxidation-antioxidation system and vascular endothelial cell function in elderly patients with chronic heart failure[J].Journal of Xinxiang Medical University,2017,34(12):751.[doi:10.7683/xxyxyxb.2017.08.024]
[8]马圆真,刘亚静,徐光华,等.基质金属蛋白酶基因启动区3个单核苷酸多态性与河南汉族群体慢性心力衰竭遗传易感性关联研究[J].新乡医学院学报,2016,33(7):568.[doi:10.7683/xxyxyxb.2016.07.005]
　MA Yuan-zhen,LIU Ya-jing,XU Guang-hua,et al.Correlation of matrix metalloproteinases promoter region three single nucleotide polymorphisms with genetic susceptibility of chronic heart failure in Henan Han population[J].Journal of Xinxiang Medical University,2016,33(12):568.[doi:10.7683/xxyxyxb.2016.07.005]
[9]郑高梅.沙库巴曲缬沙坦钠治疗老年射血分数降低的心力衰竭疗效观察[J].新乡医学院学报,2022,39(8):767.[doi:10.7683/xxyxyxb.2022.08.013]
　ZHENG Gaomei.Curative effect of sacubitril and valsartan sodium in the treatment of elderly patients with heart failure with reduced ejection fraction[J].Journal of Xinxiang Medical University,2022,39(12):767.[doi:10.7683/xxyxyxb.2022.08.013]
[10]饶小娇,边洋,王彬宇,等.老年慢性心力衰竭患者血清中胰岛素样生长因子-1和肾损伤分子-1表达水平变化及对预后的影响[J].新乡医学院学报,2023,40(4):324.[doi:10.7683/xxyxyxb.2023.04.005]
　RAO Xiaojiao,BIAN Yang,WANG Binyu,et al.Changes of serum insulin-like growth factor-1 and kidney injury molecule-1 levels in elderly patients with chronic heart failure and their influence on prognosis[J].Journal of Xinxiang Medical University,2023,40(12):324.[doi:10.7683/xxyxyxb.2023.04.005]
[11]杨秀丽,孙海燕,潘瑞阳,等.辛伐他汀对慢性心力衰竭兔心肌细胞凋亡的影响[J].新乡医学院学报,2019,36(10):907.[doi:10.7683/xxyxyxb.2019.10.002]
　YANG Xiu-li,SUN Hai-yan,PAN Rui-yang,et al.Effects of simvastatin on cardiomyocyte apoptosis in rabbits with chronic heart failure[J].Journal of Xinxiang Medical University,2019,36(12):907.[doi:10.7683/xxyxyxb.2019.10.002]
[12]赵　云,王玉华,赵国安,等.辛伐他汀对慢性心力衰竭兔心肌沉默信息调节因子2相关酶2/核因子-κB信号通路的影响[J].新乡医学院学报,2017,34(2):094.[doi:10.7683/xxyxyxb.2017.02.004]
　ZHAO Yun,WANG Yu-hua,ZHAO Guo-an,et al.Effects of simvastatin on myocardial silent mating type information regulation 2 homolog-2/nuclear factor-κB signaling pathway in rabbits with chronic heart failure[J].Journal of Xinxiang Medical University,2017,34(12):094.[doi:10.7683/xxyxyxb.2017.02.004]
[13]陈莹恩,梁　好,赵奕霖,等.辛伐他汀对慢性心力衰竭兔心功能及血清白细胞介素-18、白细胞介素-33、可溶性基质裂解素水平的影响[J].新乡医学院学报,2016,33(4):281.[doi:10.7683/xxyxyxb.2016.04.008]
　CHEN Ying-en,LIANG Hao,ZHAO Yi-lin,et al.Effects of simvastatin on cardiac function and serum interleukin-18,interleukin-33 and soluble ST2 in rabbits with chronic heart failure[J].Journal of Xinxiang Medical University,2016,33(12):281.[doi:10.7683/xxyxyxb.2016.04.008]

更新日期/Last Update: 2017-12-05