[1]吴雨婷,付 舒,岳 云,等.淫羊藿次苷Ⅱ改善自发性高血压大鼠左心室心肌细胞凋亡[J].中国药理学通报,2017,(12):1744-1749.[doi:10.3969/j.issn.1001-1978.2017.12.023]
 WU Yu-ting,FU Shu,YUE Yun,et al.Icariside Ⅱ improves left ventricular cardiomyocyte apoptosis in spontaneously hypertensive rats[J].Chinese Pharmacological Bulletin,2017,(12):1744-1749.[doi:10.3969/j.issn.1001-1978.2017.12.023]
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淫羊藿次苷Ⅱ改善自发性高血压大鼠左心室心肌细胞凋亡()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2017年12期
页码:
1744-1749
栏目:
论著
出版日期:
2017-11-20

文章信息/Info

Title:
Icariside Ⅱ improves left ventricular cardiomyocyte apoptosis in spontaneously hypertensive rats
文章编号:
1001-1978(2017)12-1744-06
作者:
吴雨婷付 舒岳 云钱志强李叶丽杨丹莉
基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,遵义医学院,贵州 遵义 563003
Author(s):
WU Yu-ting FU Shu YUE Yun Qian Zhi-qiang LI Ye-li YANG Dan-li
Key Lab of Basic Pharmacology of Ministry of Education and Joint International Research Lab of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi Guizhou 563003, China
关键词:
淫羊藿次苷 Ⅱ 自发性高血压大鼠 左室重构 心肌细胞凋亡 Bcl-2 Bax cleaved-caspase-3
Keywords:
icariside Ⅱ spontaneously hypertensive rat left ventricular remodeling cardiomyocyte apoptosis Bcl-2 Bax cleaved-caspase-3
分类号:
R-332;R284.1;R322.11;R329.25;R544.102.2;R977.6
DOI:
10.3969/j.issn.1001-1978.2017.12.023
文献标志码:
A
摘要:
目的 观察淫羊藿次苷Ⅱ(icariside Ⅱ, ICS Ⅱ)对自发性高血压大鼠(spontaneously hypertensive rats, SHR)心肌细胞凋亡的干预作用,并探讨其可能的机制。方法 30只13周龄♂ SHR随机分为模型组、ICS Ⅱ低、中、高剂量组及阳性药组(n=6); 同时,同源♂京都大鼠(WKY)作为对照组(n=6)。所有大鼠适应性饲养1周后,ICS Ⅱ低、中、高剂量组分别给予ICS Ⅱ 4、8、16 mg·kg-1(ig, qd),阳性药组给予氯沙坦20 mg·kg-1至26周龄,WKY和SHR组给予等体积双蒸水。给药12周后,测量大鼠血压,处死大鼠并分离左心室,计算左心质量指数; HE染色观察左心室病理变化; TUNEL染色观察左心室心肌细胞凋亡情况; real time RT-PCR检测左心室Bcl-2、Bax mRNA水平; Western blot检测左心室Bcl-2、Bax和cleaved-caspase-3蛋白表达。结果 相较于WKY组,SHR组大鼠血压升高,左心质量指数增加(P<0.05); 心肌细胞排列紊乱、细胞肥大明显并伴有肌丝断裂; 左室心肌细胞凋亡明显,Bax mRNA水平和蛋白表达上调,Bcl-2 mRNA水平和蛋白表达下调,Bax/Bcl-2比值升高,cleaved-caspase-3蛋白表达上调(P<0.05)。与SHR组相比,ICS Ⅱ中、高剂量组和阳性药组血压和左心质量指数下降(P<0.05); 心肌细胞排列趋于整齐、细胞肥大及心肌细胞凋亡情况均得以改善; Bax mRNA水平和蛋白表达下调,而Bcl-2 mRNA水平和蛋白表达上调,Bax/Bcl-2比值降低,cleaved-caspase-3蛋白下调(P<0.05)。结论 ICS Ⅱ可减轻SHR左心室心肌细胞凋亡,其机制与其降低血压和抑制线粒体凋亡途径相关。
Abstract:
Aim To observe the effect of icariside Ⅱ(ICS Ⅱ)on cardiomyocyte apoptosis in spontaneously hypertensive rats(SHR)and to explore its possible mechanism. Methods Thirty male 13-week-old SHRs were randomly divided into model group, ICS Ⅱ low, medium, high and positive drug group(n=6), homologous male Wistar-Kyoto rats as control group(n=6). After a week of adaptive feeding, ICS Ⅱ low, medium and high dose groups were given ICS Ⅱ 4, 8, 16 mg · kg-1(ig, qd), and the positive drug group was given losartan 20 mg·kg-1. At the same time, the WKY and SHR group were given equal volume double distilled water. After 12 weeks of administration, the blood pressure was measured in rats. Then, the rats were sacrificed and the left ventricles were separated in order to calculate the left ventricular mass index. HE staining was used to observe the pathological changes of the left ventricle, and the apoptosis of the left ventricular myocardium was detected by TUNEL staining. The expressions of Bcl-2 and Bax mRNA in left ventricle were detected by real time RT-PCR, and Bcl-2, Bax and cleaved-caspase-3 protein expressions were detected by Western blot. Results Compared with WKY group, the blood pressure and left ventricular mass index increased in SHR group(P<0.05), and the myocardial cell arrangement was disordered and the cell hypertrophy and apoptosis were obvious, accompanied by rupture of filament; the level of Bax mRNA was up-regulated(P<0.05), and Bcl-2 mRNA was down-regulated(P<0.05); the expressions of Bax and cleaved-caspase-3 protein were up-regulated(P<0.05), and the level of Bcl-2 protein was down-regulated(P<0.05), and the ratio of Bax/Bcl-2 increased(P<0.05). Compared with SHR group, the blood pressure and left ventricular mass index decreased in ICS Ⅱ middle, high group and the positive drug group(P<0.05); moreover, the arrangement of myocardial cells became more orderly, the cell hypertrophy and the apoptosis of myocardial cells were improved; the level of Bax mRNA was down-regulated and Bcl-2 mRNA was up-regulated(P<0.05); the expression of Bax and cleaved-caspase3 protein were down-regulated and the level of Bcl-2 protein was up-regulated(P<0.05); the ratio of Bax/Bcl-2 decreased(P<0.05). Conclusions ICS Ⅱ can improve the left ventricular cardiomyocytes apoptosis in SHR, and its mechanism is related to the decrease of blood pressure and the inhibition of mitochondrial apoptosis pathway.

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备注/Memo

备注/Memo:
收稿日期:2017-08-17,修回日期:2017-09-25
基金项目:国家自然科学专项基金(No 81660679)
作者简介:吴雨婷(1991- ),女,硕士生,研究方向:心血管药理学,E-mail:931813788@qq.com;
杨丹莉(1971-),女,博士,教授,硕士生导师,研究方向:心血管药理学,通讯作者,Tel:0851-28643568, E-mail:zmuyangdanli@foxmail.com
更新日期/Last Update: 2017-11-20