中国药理学通报2017,Vol.33Issue(12):1744-1749,6.DOI:10.3969/j.issn.1001-1978.2017.12.023
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
Icariside Ⅱ improves left ventricular cardiomyocyte apoptosis in spontaneously hypertensive rats
摘要
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),ho-mologous male Wistar-Kyoto rats as control group (n =6). After a week of adaptive feeding,ICS Ⅱ low,me-dium 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 ventricu-lar 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 detec-ted by Western blot. Results Compared with WKY group,the blood pressure and left ventricular mass in-dex increased in SHR group (P < 0. 05),and the my-ocardial 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-regu-lated (P < 0. 05 ),and the ratio of Bax / Bcl-2 in-creased (P < 0. 05). Compared with SHR group,the blood pressure and left ventricular mass index de-creased 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 hyper-trophy and the apoptosis of myocardial cells were im-proved;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 de-creased (P < 0. 05). Conclusions ICS Ⅱ can im-prove the left ventricular cardiomyocytes apoptosis in SHR,and its mechanism is related to the decrease of blood pressure and the inhibition of mitochondrial ap-optosis pathway.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-3Key words
icariside Ⅱ/spontaneously hypertensive rat/left ventricular remodeling/cardiomyocyte apopto-sis/Bcl-2/Bax/cleaved-caspase-3分类
医药卫生引用本文复制引用
吴雨婷,付舒,岳云,钱志强,李叶丽,杨丹莉..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,2017,33(12):1744-1749,6.基金项目
国家自然科学专项基金(No 81660679) (No 81660679)