[1]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):094-98.[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(2):094-98.[doi:10.7683/xxyxyxb.2017.02.004]
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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
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
34
期数:
2017年2
页码:
094-98
栏目:
基础研究
出版日期:
2017-02-05

文章信息/Info

Title:
Effects of simvastatin on myocardial silent mating type information regulation 2 homolog-2/nuclear factor-κB signaling pathway in rabbits with chronic heart failure
作者:
赵　云1; 王玉华2; 赵国安3; 赵奕霖4
（1.新乡医学院第三附属医院心内科，河南　新乡　453003；2.新乡医学院第三附属医院泌尿外科，河南　新乡　453003；3.新乡医学院第一附属医院心内科，河南　卫辉　453100；4.新乡医学院三全学院，河南　新乡　453003）
Author(s):
ZHAO Yun1; WANG Yu-hua2; ZHAO Guo-an3; ZHAO Yi-lin4
(1.Department of Cardiology，the Third Affiliated Hospital of Xinxiang Medical University，Xinxaing 453003，Henan Province，China；2.Department of Urinary Surgery，the Third Affiliated Hospital of Xinxiang Medical University，Xinxaing 453003，Henan Province，China；3.Department of Cardiology，the First Affiliated Hospital of Xinxiang Medical University，Weihui 453100，Henan Province，China；4.Sanquan College of Xinxiang Medical University，Xinxiang 453003，Henan Province，China)
关键词:
辛伐他汀; 慢性心力衰竭; 沉默信息调节因子2相关酶2; 核因子-κB
Keywords:
simvastatin; chronic heart failure; silent mating type information regulation 2 homolog-2; nuclear factor-κB
分类号:
R541.6
DOI:
10.7683/xxyxyxb.2017.02.004
文献标志码:
A
摘要:
目的　研究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（SIRT2）/核因子-κB(NF-κB)信号通路的影响。方法　24只雄性新西兰大白兔随机分为正常组、心力衰竭组和辛伐他汀组，每组8只。心力衰竭组和辛伐他汀组兔每日经耳缘静脉注射1 g·L-1阿霉素生理盐水注射液建立慢性心力衰竭模型，正常组兔经耳缘静脉注射相同剂量的生理盐水注射液；同时，辛伐他汀组兔每日给予1.5 mg·kg-1辛伐他汀灌胃，正常组和心力衰竭组兔给予相同剂量生理盐水灌胃，均连续12周。造模结束时各组兔做心脏超声观察心功能情况，并处死取左心室做石蜡包埋切片，苏木精-伊红染色观察心肌组织变化，免疫组织化学法检测各组兔心肌细胞中SIRT2、NF-κB蛋白表达，反转录-聚合酶链式反应检测心肌组织中SIRT2 mRNA、NF-κB mRNA的变化。结果　与正常组比较，心力衰竭组和辛伐他汀组兔的左心室射血分数（LVEF)降低（P<0.01），左心室舒张末期内径（LVDd）增高（P<0.01）；辛伐他汀组兔的LVEF高于心力衰竭组（P<0.01)，LVDd低于心力衰竭组（P<0.01)。与正常组比较，心力衰竭组兔心肌细胞SIRT2蛋白阳性表达率降低（P<0.01），辛伐他汀组兔心肌细胞SIRT2蛋白阳性表达率升高（P<0.01），且辛伐他汀组兔心肌细胞SIRT2蛋白阳性表达率高于心力衰竭组（P<0.01）。与正常组比较，心力衰竭组兔心肌细胞NF-κB蛋白阳性表达率升高（P<0.01），辛伐他汀组兔心肌细胞NF-κB蛋白阳性表达率降低（P<0.01），且辛伐他汀组兔心肌细胞NF-κB蛋白阳性表达率低于心力衰竭组（P<0.01）。与正常组比较，心力衰竭组兔心肌组织中SIRT2 mRNA相对表达量降低（P<0.05），辛伐他汀组兔心肌组织中SIRT2 mRNA相对表达量升高（P<0.01）。与心力衰竭组比较，辛伐他汀组兔心肌组织中SIRT2 mRNA相对表达量升高（P<0.01）。与正常组比较，心力衰竭组兔心肌组织中NF-κB mRNA相对表达量升高（P<0.01），辛伐他汀组兔心肌组织中NF-κB mRNA相对表达量降低（P<0.01）；与心力衰竭组比较，辛伐他汀组兔心肌组织中NF-κB mRNA相对表达量降低（P<0.01）。结论　辛伐他汀可能通过上调SIRT2的表达而抑制NF-κB的表达，从而改善兔的心功能。
Abstract:
Objective　To study the effect of simvastatin on silent mating type information regulation 2 homolog-2(SIRT2)/nuclear factor-κB(NF-κB) signaling pathway in rabbits with chronic heart failure.Methods　Twenty-four New Zealand male rabbits were randomly divided into normal group，chronic heart failure(CHF) group and simvastatin group，with eight rabbits in each group.The rabbits in the CHF group and simvastatin group were daily injected with 1 g·L-1 adriamycin through ear vein to establish CHF models.The rabbits in the normal group were injected with the same dose of saline injection.At the same time，the rabbits in simvastatin group were treated with 1.5 mg·kg-1 simvastatin by intragastric administration daily，and the rabbits in normal group and CHF group were treated with the same dose of physiological saline by intragastric administration daily.All the rabbits were dealt for twelve weeks.The heart function of the rabbits in the groups was observed by ultrasonography at the end of modeling.The rabbits were sacrificed and the left ventricles were made into paraffin embedded sections.The histological changes of myocardium were observed by hematoxylin eosin staining.The expression of SIRT2 and NF-κB protein in myocardial tissue of rabbits in the groups was detected by immunohistochemical method.The expression of SIRT2 mRNA and NF-κB mRNA was detected by reverse transcription polymerase chain reaction.Results　Compared with the normal group，the left ventricular ejection fraction(LVEF) of rabbits was significantly decreased (P<0.01)，and the left ventricular end diastolic dimension(LVDd) of rabbits was significantly increased in the simvastatin group and CHF group(P<0.01).Compared with the CHF group，the LVEF of rabbits was significantly increased (P<0.01)，and the LVDd of rabbits was significantly decreased in the simvastatin group (P<0.01).The positive expression rate of SIRT2 protein in myocardial cells of rabbits in CHF group was significantly lower than that in normal group (P<0.01).The positive expression rate of SIRT2 protein in myocardial cells of rabbits in simvastatin group was significantly higher than that in normal group and CHF group (P<0.01).The positive expression rate of NF-κB protein in myocardial cells of rabbits in CHF group was significantly higher than that in normal group (P<0.01).The positive expression rate of NF-κB protein in myocardial cells of rabbits in simvastatin group was significantly lower than that in normal group and CHF group (P<0.01).The relative expression of SIRT2 mRNA in myocardial cells of rabbits in CHF group was significantly lower than that in normal group (P<0.05).The relative expression of SIRT2 mRNA in myocardial cells of rabbits in simvastatin group was significantly higher than that in normal group and CHF group (P<0.01).The relative expression of NF-κB mRNA in myocardial cells of rabbits in CHF group was significantly higher than that in normal group (P<0.01).The relative expression of NF-κB mRNA in myocardial cells of rabbits in simvastatin group was significantly lower than that in normal group and CHF group (P<0.01).Conclusion　Simvastatin may inhibit the expression of NF-κB by up-regulating the expression of SIRT2 in myocardial cells of rabbits，which can improve cardiac function of rabbits.

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更新日期/Last Update: 2017-02-05