摘要
目的探讨异鼠李素保护阿霉素所致心肌损伤的作用及可能机制。方法除空白对照组外,模型对照组,异鼠李素2.5、5、10 mg·kg^(-1)组,阳性对照组(20 mg·kg^(-1)右丙亚胺)均建立阿霉素心肌损伤模型,每组10只大鼠。采用TUNEL法检测心肌细胞凋亡率;激光扫描共聚焦显微镜测定心肌细胞内钙离子浓度;罗丹明123(Rho123)荧光探针标记流式细胞仪检测和分析线粒体跨膜电位(△ψm);蛋白免疫印迹法检测Cyt-c和Caspase-9的表达水平。结果与空白对照组相比,阿霉素心肌损伤模型对照组细胞凋亡率由(1.1±0.22)%明显升高至(17.5±2.03)%、胞浆内钙离子浓度由(115.2±10.07)μmol·L^(-1)明显升高至(478.3±19.45)μmol·L^(-1)、线粒体膜电位△ψmlow的细胞数目占比由(3.63±0.34)%明显升高至(39.86±0.53)%、Cyt-c和Caspase-9表达明显升高;而5、10mg·kg^(-1)异鼠李素明显缓解了上述指标的变化[凋亡率降为(5.6±0.93)%,胞浆内钙离子浓度平均值为降为(298.2±10.54)μmol·L^(-1),线粒体膜电位△ψmlow的细胞数目占比降至(17.64±0.41)%,Cyt-c、Caspase-9蛋白表达明显下降];且与阳性对照组相比结果相近。结论异鼠李素可减少阿霉素所致心肌细胞凋亡率而保护心肌,其机制可能与改善细胞内钙离子稳态、线粒体功能、降低Cyt-c和Caspase-9蛋白表达等线粒体凋亡通路相关指标有关。
Objective To explore the protection effect of isorhamnetin on myocardial cell apoptosis induced by adriamycin and the possible mechanism. Methods Except for in the blank control group, myocardial injury model induced by adriamycin was established in the model control group. The isorhamnetin （2.5, 5, and 10 mg · kg ^- 1） groups and the positive control dexrazoxane 20 mg · kg ^- 1 group, 10 rats in each. Apoptosis of the myocardial cells was determined by TUNEL method. Intracellular calcium in the myocardial cells were measured by laser scanning confocal. Mitochondrial transmembrane potential （△ψm） was measured by flow cytometry. Western blot detected Cyt-c and caspase-9 expression level. Results Compared with the blank control group, the apoptosis rates, intracellular calcium concentration, cell number of △ψm^low, expression levels of Cyt-c and caspase-9 significantly were increased in the model control group. Isorhamnetin improved the above indexes significantly （P 〈 0.05）. Conclusion Isorhamnetin can reduce the rate of apoptosis in myocardial cells induced by adriamycin, whose mechanism may be related with the improvement of intracellular calcium homeo- stasis, mitochondrial function, and reduction of Cyt-c and caspase-9 expression.
出处
《中南药学》
CAS
2017年第7期915-918,共4页
Central South Pharmacy
基金
漯河医学高等专科学校自然科学项目(2010S09)
漯河医学高等专科学校青年骨干教师科研基金
关键词
异鼠李素
阿霉素
钙超载
线粒体
细胞凋亡
isorhamnetin
adriamycin
calcium overload
mitochondria
apoptosis
