摘要
目的:探究番茄红素对四氯化碳(carbon tetrachloride,CCl_4)诱导的急性肝损伤小鼠内质网应激(endoplasmic reticulum stress,ERS)的作用及作用机制。方法:灌胃给予番茄红素7 d后,用CCl_4复制小鼠急性肝损伤模型,试剂盒检测肝组织乳酸脱氢酶(lactic dehydrogenase,LDH)活性;TUNEL检测细胞凋亡;Western blot检测ERS相关蛋白及PI3K/Akt通路标记蛋白的表达。结果:番茄红素能降低肝脏LDH(P<0.01)活性,同时还可明显抑制细胞凋亡(P<0.05);此外。番茄红素能明显抑制ERS相关蛋白葡萄糖调节蛋白(glucose regulated protein 78kda,GRP78)、激活转录因子(activating trnsfection factor-6,ATF-6)、p-肌醇酶-1α(inositol requiring enzyme,p-IRE-1α)、p-真核起始因子-2α(eukaryotic initiation factor-2α,p-e IF-2α)和caspase-12的表达(P<0.05),升高p-Akt/Akt的比值(P<0.05)。结论:番茄红素可通过抑制内质网氧化应激减轻CCl4诱导的肝损伤,其机制可能与促进PI3K/Akt通路激活有关。
AIM：To investigate the effects and mechanism of lycopene on endoplasmic reticulum stress（ERS） in CCl4-induced acute liver injury mice.METHODS：The mice were treated with lycopene（i.g.） and acute hepatic injury was induced by carbon tetrachloride（CCl4,i.p.）.The activity of lactic dehydrogenase（LDH） in liver tissue was measured by kit.The apoptosis was measured by TUNEL assay.Western blot was performed for proteins.RESULTS：Lycopene decreased the activity LDH（P〈0.01） significantly.Meanwhile,lycopene inhibited apoptosis makedly（P〈0.05）.In addition,pretreatment with lycopene inhibited the expressions of glucose regulated protein 78 kda（GRP78）,activating trnsfection factor-6（ATF-6）,inositol requiring enzyme（p-IRE-1α）,eukaryotic initiation factor-2α（p-e IF-2α） and caspase-12（P〈0.05）.Furthermore,the ratio of p-Akt/Akt was down-regulated by lycopene（P〈0.05）.CONCLUSION：Lycopene alleviates CCl4-induced liver injury by inhibiting ER stress,and the mechanism might be associated with the activation of PI3 K/Akt signaling pathway.
作者
廖笑玲
吴亮
林宗泽
叶剑
LIAO Xiaoling;WU Liang;LIN Zongze;YE Jian(Ruian People＇s Hospital,Ruian 325200,Zhejiang,China)
出处
《中国临床药理学与治疗学》
CAS
CSCD
2018年第7期770-775,共6页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
浙江省自然科学基金项目(LQ14H060003)
关键词
番茄红素
急性肝损伤
内质网应激
lycopene
acute liver injury
endoplasmic reticulum stress
