张晓雯;郑舒泽;李欣;孙成宏;曾克武;
ZHANG Xiao-wen;ZHENG Shu-ze;LI Xin;SUN Cheng-hong;ZENG Ke-wu;State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co., Ltd.;

• 1:北京大学药学院天然药物及仿生药物国家重点实验室
• 2:鲁南制药集团股份有限公司中药制药共性技术国家重点实验室

摘要(Abstract)：

探究首荟通便胶囊提取物改善胃肠道间质细胞能量代谢的细胞药理学机制。以胃肠道间质细胞GIST-882为模型,通过检测细胞存活率、细胞形态学考察首荟通便胶囊提取物(10,20,50,100μg·mL~(-1))对胃肠道间质细胞增殖能力的影响,进而检测线粒体形态学、线粒体膜电位、异柠檬酸脱氢酶活性以及细胞三磷酸腺苷(ATP)水平,同时Western blot法检测SCF/c-Kit信号通路以及CDK2/cyclin A细胞周期信号通路相关蛋白的表达,考察首荟通便胶囊促胃肠道间质细胞能量代谢的潜在分子机制。结果显示,首荟通便胶囊可以剂量依赖性地促进GIST-882细胞的增殖,显著提高细胞中线粒体结构完整性,同时升高线粒体膜电位。进一步研究表明,首荟通便胶囊可上调线粒体异柠檬酸脱氢酶的活性,进而促进细胞中ATP含量升高,促进SCF/c-Kit信号通路以及CDK2/cyclin A细胞周期信号通路相关蛋白的表达。以上结果表明,首荟通便胶囊能增强胃肠道间质细胞的能量代谢并促进其增殖,其潜在机制可能是通过上调线粒体异柠檬酸脱氢酶活性进而加速ATP的合成,并促进SCF/c-Kit以及CDK2/cyclin A信号通路实现的。
Mechanism study was performed to explore how Shouhui Tongbian Capsules promotes energy metabolism of gastrointestinal stromal cells. In this study, gastrointestinal stromal cells line GIST-882 was used as the model to explore energy metabolism regulation effects of Shouhui Tongbian Capsules extract(10, 20, 50 and 100 μg·mL~(-1)) by measuring the cell proliferation, ATP level, mitochondrial membrane potential, and mitochondrial isocitrate dehydrogenase activity. Meanwhile, Western blot was used to detect the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Our results showed that Shouhui Tongbian Capsules promoted cell proliferation and increased ATP level of gastrointestinal stromal cells. In addition, Shouhui Tongbian Capsules obviously improved mitochondrial structural integrity, and increased mitochondrial membrane potential in GIST-882 cells. Mechanism study revealed that Shouhui Tongbian Capsules increased mitochondrial isocitrate dehydrogenase activity and up-regulated the proteins expression of SCF/c-Kit and CDK2/cyclin A signaling pathways. Collectively, our study indicated that Shouhui Tongbian Capsules promoted the energy metabolism for gastrointestinal stromal cells proliferation by activating mitochondrial isocitrate dehydrogenase to induce ATP production, as well as activating SCF/c-Kit and CDK2/cyclin A signaling pathways.

关键词(KeyWords)： 能量代谢;首荟通便胶囊;胃肠道间质细胞;线粒体功能;异柠檬酸脱氢酶
energy metabolism;Shouhui Tongbian Capsules;gastrointestinal stromal cells;mitochondrial function;isocitrate dehydrogenase

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81973505,81773932)

作者(Author): 张晓雯;郑舒泽;李欣;孙成宏;曾克武;
ZHANG Xiao-wen;ZHENG Shu-ze;LI Xin;SUN Cheng-hong;ZENG Ke-wu;State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine,Lunan Pharmaceutical Group Co., Ltd.;

Email:

DOI: 10.19540/j.cnki.cjcmm.20201209.401

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