摘要
目的观察淫羊藿次苷Ⅱ(icarisideⅡ,ICSⅡ)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、ICSⅡ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,ICSⅡ低、中、高剂量组分别给予ICSⅡ4、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 RTPCR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,ICSⅡ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 ICSⅡ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。
AimTo observe the effect of icarisideⅡ(ICSⅡ)on cardiomyocyte apoptosis in spontaneously hypertensive rats(SHR)and to explore its possible mechanism.MethodsThirty male13week old SHRs were randomly divided into model group,ICSⅡlow,medium,high and positive drug group(n=6),homologous male Wistar Kyoto rats as control group(n=6).After a week of adaptive feeding,ICSⅡlow,medium and high dose groups were given ICSⅡ4,8,16mg·kg-1(ig,qd),and the positive drug group was given losartan20mg·kg-1.At the same time,the WKY and SHR group were given equal volume double distilled water.After12weeks 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 Bcl2and Bax mRNA in left ventricle were detected by real time RT PCR,and Bcl2,Bax and cleaved caspase3protein expressions were detected by Western blot.ResultsCompared with WKY group,the blood pressure and left ventricular mass index increased in SHR group(P<005),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 wasup regulated(P<005),and Bcl2mRNA was down regulated(P<005);the expressions of Bax and cleaved caspase3protein were up regulated(P<005),and the level of Bcl2protein was down regulated(P<005),and the ratio of Bax/Bcl2increased(P<005).Compared with SHR group,the blood pressure and left ventricular mass index decreased in ICSⅡmiddle,high group and the positive drug group(P<005);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 Bcl2mRNA was up regulated(P<005);the expression of Bax and cleaved caspase3protein were down regulated and the level of Bcl2protein was up regulated(P<005);the ratio of Bax/Bcl2decreased(P<005).ConclusionsICSⅡcan 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.
作者
吴雨婷
付舒
岳云
钱志强
李叶丽
杨丹莉
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 Guizhou563003, China;Zunyi Medical University, Zunyi Guizhou563003, China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2017年第12期1744-1749,共6页
Chinese Pharmacological Bulletin
基金
国家自然科学专项基金(No 81660679)
