羟基红花黄色素A缓解大鼠心肌细胞凋亡作用的研究  

Inhibition of hydroxysafflor yellow A against rat cardiomyocyte apoptosis

作　　者：金鸣[1] 董宁宁[1] 吴伟[1] 李金荣[1] 臧宝霞[1] 童静[1] 

机构地区：[1]首都医科大学附属北京安贞医院-北京市心肺血管疾病研究所药理研究室,北京100029

出　　处：《中草药》2009年第6期924-930,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(30171146);北京市中医局科技资助项目(JJ-2006-26)

摘　　要：目的以整体和离体实验观察羟基红花黄色素A(HSYA)缓解心肌细胞凋亡的作用。方法以异丙肾上腺素(ISO)造成大鼠急性心肌缺血,以TUNEL法检测心肌组织细胞凋亡,免疫组化法和RT-PCR法观察心肌组织中bax、bcl-2基因表达的变化;用缺糖缺氧/再复氧模型诱导原代培养心肌细胞凋亡,以PI流式细胞法观察凋亡情况,以Rhodamine 123荧光法考察线粒体膜电位的变化。结果60、120、240 mg/kg HSYA ip给药可以减轻心肌缺血大鼠的线粒体肿胀、核凝集及固缩,降低心肌细胞凋亡率(P<0.01),下调心肌组织Bax蛋白(P<0.05)及bax mRNA的表达(P<0.01)。0.64、1.3、2.5 mmol/L HSYA可减少缺氧/再复氧造成的细胞凋亡(P<0.05),且可缓解该损伤造成的心肌线粒体膜电位下降(P<0.05)。结论抑制心肌细胞凋亡是HSYA缓解心肌缺血的重要机制。Objective To investigate the inhibitory effect of hydroxysafflor yellow A （HSYA） against cardiomyocyte apoptosis. Methods Rat myocardial apoptosis was induced by ip isoproterenol （ISO） and then HSYA was ip given to alleviate the apoptosis. Rat neonatal cardiomyocyte apoptosis was triggered by oxygen/glucose-deprivation/reperfusion （OGDR） injury. Cardiac tissue was observed by transmission electron microscopy （TEM） and cardiac cell apoptosis was assayed by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEI.） staining. Bcl-2 and bax gene expression was observed by immunohistochemical staining and RT-PCR. The effect of HSYA to inhibit cardio myocyte apoptosis was assayed with the Flow Cyto Meter. Rhodamine 123 staining was used to measure the change of mitochondrial membrane potential. Results TEM showed that mitoehondrion swelling and nucleus pyknosis were alleviated by HSYA treatment. It was shown by TUNEL staining that 60, 120, or 240 mg/kg HSYA decreased the apotosis rate of cardiomyoeyte in rats with myocardial ischemia. In 120 mg/kg HSYA-treated rats, Bax expression was down-regulated compared with NS treated rats. In cultured OGDR cardiomyoeytes, HSYA inhibited the decrease in mitochondrial membrane potential. Conclusion The mechanisms involved in the cardioprotective effect of HSYA are inhibition of cardiomyocyte apoptosis.

关 键 词：羟基红花黄色素A(HSYA) 凋亡 心肌缺血 线粒体 

分 类 号：R286.2[医药卫生—中药学]