摘要
内质网应激(endoplasmic reticulum stress,ERS)启动的细胞凋亡是近年才发现的一种新的凋亡途径,本研究从ERS途径探讨凉血化瘀方对肿瘤坏死因子α(TNF-α)和D-氨基半乳糖(D-GalN)所致肝细胞凋亡的保护作用。研究发现,TNF-α和D-GalN可明显抑制L02肝细胞增殖,诱导细胞凋亡,使细胞质内游离钙离子含量明显上升,并使ERS凋亡相关信号分子磷酸化PERK,磷酸化elF2α,cleaved Caspase-12,GRP78,CHOP的蛋白表达显著增加。不同浓度的凉血化瘀方作用后,与TNF-α/GalN损伤组相比,可显著减轻L02肝细胞的增殖抑制、减少细胞的凋亡,抑制细胞质内游离钙离子含量的增高,并使磷酸化PERK,磷酸化elF2α,cleaved Caspase-12,GRP78,CHOP的蛋白表达量呈逐渐下降的趋势。这些发现说明:凉血化瘀方对TNF-α和D-GalN所诱导的肝细胞凋亡具有抑制作用,其机制可能与维持内质网腔钙稳态平衡和下调ERS凋亡相关信号分子磷酸化PERK,磷酸化elF2α,cleaved Caspase-12,GRP78,CHOP的表达有关。
Endoplasmic reticulum stress （ERS） is a new pathway inducing cell apoptosis that has been discovered in recent years. This study focused on the protective effect of Liangxue Huayu recipe （LHR） on tumor necrosis factor-α （TNF-α） and D-GaIN- induced hepatocyte apoptosis. It found that TNF-α and D-GaIN could obviously inhibit hepatocyte proliferation, induce cell apoptosis, and significantly increase free calcium ions in cytoplasms, as well as protein expressions of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2α, cleaved Caspase-12, GRP78 and CHOP. After the administration of LHR of different concentrations, compared with the TNF-α/GalN injury group, LHR could significantly alleviated L02 hepatocyte proliferation, de- creased cell apoptosis, inhibited growth of intracytoplasmic free calcium content, and gradually reduced the protein expressions of phos- phorylated PERK, phosphorylated elF2α, cleaved Caspase-12, GRP78 and CHOP. These findings indicated that LHR has the inhibito- ry effect on TNF-α and D-GaiN-induced hepatocyte apoptosis. Its mechanism may be related to down-regnlation of ERS apoptosis-relat- ed signal molecules phosphorylated PERK, phosphorylated elF2a, cleaved Caspase-12, GRP78 and CHOP that maintain calcium ho- meostasis in endoplasmic reticulum.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2013年第20期3544-3548,共5页
China Journal of Chinese Materia Medica
基金
国家自然科学基金面上项目(81072777
81273638)
江苏省高校优势学科建设工程项目(PAPD)
江苏省高等学校大学生创新训练计划项目(011042001000
640)
关键词
凉血化瘀方
肝细胞凋亡
内质网应激
Liangxue Huayu recipe （LHR）
hepatocyte apoptosis
endoplasmic reticulum stress （ERS）
