[1]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):907-911.[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(10):907-911.[doi:10.7683/xxyxyxb.2019.10.002]
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辛伐他汀对慢性心力衰竭兔心肌细胞凋亡的影响
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
36
期数:
2019年10
页码:
907-911
栏目:
基础研究
出版日期:
2019-10-05

文章信息/Info

Title:
Effects of simvastatin on cardiomyocyte apoptosis in rabbits with chronic heart failure
作者:
杨秀丽1; 孙海燕1; 潘瑞阳1; 赵奕霖1; 杨　萌1; 黄宏伟1; 王显良1; 赵国安2
（1.新乡医学院第三附属医院心血管内科，河南　新乡　453003；2.新乡医学院第一附属医院心血管内科，河南　卫辉　453100）
Author(s):
YANG Xiu-li1; SUN Hai-yan1; PAN Rui-yang1; ZHAO Yi-lin1; YANG Meng1; HUANG Hong-wei1; WANG Xian-liang1; ZHAO Guo-an2
(1.Department of Cardiology,the Third Affiliated Hospital of Xinxiang Medical University,Xinxiang 453003,Henan Province,China;2.Department of Cardiology,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China)
关键词:
慢性心力衰竭; 辛伐他汀; 细胞凋亡; 可溶性Fas; p53
Keywords:
chronic heart failure; simvastatin; apoptosis; soluble Fas; p53
分类号:
R541.6
DOI:
10.7683/xxyxyxb.2019.10.002
文献标志码:
A
摘要:
目的　探讨辛伐他汀对慢性心力衰竭（CHF）兔心肌细胞凋亡的影响及其机制。方法　将36只新西兰雄性大耳兔随机分为正常对照组、CHF组和辛伐他汀组，每组12只。CHF组和辛伐他汀组兔经耳缘静脉注射注射用盐酸多柔比星1.5 mg·kg-1，每周1次，连续10周，注射完成后再观察2周；正常对照组兔经耳缘静脉注射生理盐水；辛伐他汀组兔在首次注射多柔比星时开始给予辛伐他汀1.5 mg·kg-1灌胃，每日1次，连续12周。12周后，3组兔行超声心动图检查，分别测量左心室收缩末期内径（LVESD）、左心室舒张末期内径（LVEDD）、左心室短轴缩短率（LVFS）及左心室射血分数（LVEF）。心脏超声心动图检查后，兔颈动脉取血5 mL，采用酶联免疫吸附试验检测血清可溶性Fas（sFas）水平。采用空气栓塞法处死兔，游离左心室心肌，采用末端脱氧核苷酰基转移酶介导性dUTP切口末端标记法检测心肌细胞凋亡情况，并计算细胞凋亡指数；采用免疫组织化学法检测心肌细胞中p53蛋白表达，并计算p53蛋白阳性表达率。结果　辛伐他汀组和CHF组兔LVESD、LVEDD大于正常对照组（P<0.05），LVEF、LVFS显著低于正常对照组（P<0.05）；辛伐他汀组兔LVESD、LVEDD小于CHF组（P<0.05），LVEF、LVFS高于CHF组（P<0.05）。正常对照组、CHF组和辛伐他汀组兔血清sFas水平分别为（8.42±0.14）、（11.7±0.55）、（9.43±0.35）mg·L-1，CHF组和辛伐他汀组兔血清sFas水平高于正常对照组（P<0.05），辛伐他汀组兔血清sFas水平低于CHF组（P<0.05）。正常对照组、CHF组和辛伐他汀组兔心肌细胞凋亡指数分别为1.08±0.12、16.13±1.17、4.86±0.11，CHF组和辛伐他汀组兔心肌细胞凋亡指数高于正常对照组（P<0.05），辛伐他汀组兔心肌细胞凋亡指数低于CHF组（P<0.05）。正常对照组、CHF组和辛伐他汀组兔心肌细胞p53蛋白阳性表达率分别为18.62±0.41、45.39±0.68、33.17±0.52，CHF组和辛伐他汀组兔心肌细胞p53蛋白阳性表达率高于正常对照组（P<0.05），辛伐他汀组兔心肌细胞p53蛋白阳性表达率低于CHF组（P<0.05）。结论　辛伐他汀可以显著改善CHF大鼠的心功能，抑制心室重构，其机制可能与其抑制Fas/FasL信号系统及心肌细胞凋亡有关。
Abstract:
Objective　To investigate the effect and mechanism of simvastatin on cardiomyocyte apoptosis in rabbits with chronic heart failure(CHF)．Methods　Thirty-six male immature new Zealand rabbits were randomly divided into normal control group,CHF group and simvastatin group,with twelve rabbits in each group.The rabbits in the CHF group and simvastatin group were injected with doxorubicin hydrochloride 1.5 mg·kg-1 via ear vein，once a week for 10 weeks,then they were observed for 2 weeks.The rabbits in the normal control group were injected with saline through ear vein.The rabbits in the simvastatin group were injected with simvastatin 1.5 mg·kg-1 from the first injection of doxorubicin,once a day for 12 weeks.After 12 weeks,the left ventricular end-systolic dimension (LVESD),left ventricular end-diastolic dimension (LVEDD),left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) of rabbits in the three groups were measured by echocardiography.After echocardiography,5 mL of carotid artery blood was taken from rabbits and the serum soluble Fas (sFas) level was detected by enzyme linked immunosorbent assay.The rabbits were sacrificed by air embolization to obtain the left ventricular myocardium.Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP incision end labeling method,and the apoptotic index was calculated.The expression of p53 protein in cardiomyocytes was detected by immunohistochemistry,and the positive expression rate of p53 protein was calculated.Results　The LVESD and LVEDD of rabbits in the simvastatin group and CHF group were higher than those in the normal control group (P<0.05),while the LVEF and LVFS of rabbits in the simvastatin group and CHF group were significantly lower than those in the normal control group (P<0.05).The LVESD and LVEDD of rabbits in the simvastatin group were lower than those in the CHF group (P<0.05),and the LVEF and LVFS of rabbits in the simvastatin group were higher than those in the CHF group (P<0.05).The serum sFas level in the normal control group,CHF group and simvastatin group was (8.42±0.14),(11.7±0.55) and (9.43±0.35) mg·L-1,respectively.The level of serum sFas in the CHF group and simvastatin group was higher than that in the normal control group (P<0.05),and the level of serum sFas in the simvastatin group was lower than that in the CHF group (P<0.05).The apoptotic index of myocardial cells in the normal control group,CHF group and simvastatin group was 1.08±0.12,16.13±1.17 and 4.86 ±0.11,respectively.The apoptotic index of cardiomyocytes in the CHF group and simvastatin group was higher than that in the normal control group (P<0.05),and the apoptotic index of cardiomyocytes in the simvastatin group was lower than that in the CHF group (P<0.05).The positive expression rate of p53 protein in myocardial cells of rabbits in the normal control group,CHF group and simvastatin group was 18.62±0.41,45.39±0.68 and 33.17±0.52,respectively.The positive expression rate of p53 protein in cardiomyocytes of rabbits in the CHF group and simvastatin group was higher than that in the normal control group (P<0.05),and the positive expression rate of p53 protein in myocardial cells of rabbits in the simvastatin group was lower than that in the CHF group (P<0.05).Conclusion　Simvastatin can significantly improve cardiac function and inhibit cardiac remodeling in rats with CHF,the mechanism may be related to inhibiting Fas/FasL signaling system and cardiomyocyte apoptosis.

参考文献/References:

［1］　FUJITA T,ISHIKAWA Y.Apoptosis in heart failure:the role of the β-adrenergic receptor-mediated signaling pathway and p53-mediated signaling pathway in the apoptosis of cardiomyocytes［J］.Circ J,2011,75(8):1811-1818.
［2］　KONCZ G,HANCZ A,CHAKRABANDHU K,et al.Vesicles rele-ased by activated T cells induce both Fas-mediated RIP-dependent apoptotic and Fas-independent nonapoptotic cell deaths［J］.J Immunol,2012,189(6):2815-2823.
［3］　GOGIRAJU R,XU X,BOCHENEK M L,et al.Endothelial p53 de-letion improves angiogenesis and prevents cardiac fibrosis and heart failure induced by pressure overload in mice［J］.J Am Heart Assoc,2015,4(2):e001770.
［4］　刘茜，魏玲.p53基因及其相关蛋白与心血管疾病关系的研究进展［J］.医学综述，2013，19（20）：3692-3694.
［5］　CAO S,ZENG Z,WANG X,et al.Pravastatin slows the progression of heart failure by inhibiting the c-Jun N-terminal kinase-mediated intrinsic apoptotic signaling pathway［J］.Mol Med Rep,2013,8(4):1163-1168.
［6］　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）：94-98．
［7］　LU F H,FU S B,LENG X,et al.Role of the calcium-sensing receptor in cardiomyocyte apoptosis via the sarcoplasmic reticulum and mitochondrial death pathway in cardiac hypertrophy and heart failure［J］.Cell Physiol Biochem,2013,31(4/5):728-743.
［8］　杨秀丽，刘迎春，冉倩，等.辛伐他汀对慢性心力衰竭幼兔心肌嗜铬粒蛋白A、细胞凋亡信号调节激酶1表达的影响［J］.中华实用儿科临床杂志，2017，32（5）：365-368.
［9］　赵慧，王雄，魏晓倩.异丙肾上腺素预处理对心肌缺血再灌注损伤大鼠心肌细胞凋亡及氧化应激的影响［J］.中西医结合心脑血管病杂志，2017，15（1）：36-40.
［10］　OH H K,LEE E,JANG H N,et al.hnRNP A1 contacts exon 5 to promote exon 6 inclusion of apoptotic Fas gene［J］.Apoptosis,2013,18(7):825-835.
［11］　KINUGAWA T,KATO M,YAMAMOTO K,et al.Proinflammatory cytokine activation is linked to apoptotic mediator,soluble Fas level in patients with chronic heart failure［J］.Int Heart J,2012,53(3):182-186.
［12］　姜丁文，刘畅.核因子-κB和p53在波动性高糖致心肌细胞凋亡中的作用［J］.医学与哲学，2015，36（6B）：62-64.
［13］　胡沙雅，何学华，阮涛，等.阿霉素致扩张型心肌病心肌损伤中各项相关指标变化［J］.湖南师范大学学报（医学版），2014，11（1）：24-26.
［14］　YOSHIDA M,SHIOJIMAL I,IKEDA H,et al.Chronic doxorubicin cardiotoxicity is mediated by oxidative DNA damage-ATM-p53-apoptosis pathway and attenuated by pitavastatin through the inhibition of Rac1 activity［J］.J Mol Cell Cardiol,2009,47(5):698-705.
［15］　ZHU W,SOONPAA M H,CHEN H,et al.Acute doxorubicin cardiotoxicity is associated with p53-induced inhibition of the mammaliantarget of rapamycin pathway［J］.Circulation,2009,119(1):99-106.
［16］　陈莹恩，杨秀丽，赵奕霖，等.辛伐他汀对慢性心力衰竭幼兔心肌凋亡及 氧化应激机制的影响［J］.中华实用儿科临床杂志，2017，32（13）：1022-1025.

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更新日期/Last Update: 2019-10-05