番茄红素抑制内质网应激从而减轻CCl4诱导的小鼠急性肝损伤

doi:10.12092/j.issn.1009-2501.2018.07.008

摘要/Abstract

摘要：

目的: 探究番茄红素对四氯化碳 (carbon tetrachloride, CCl₄)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CCl₄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-eIF-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。

关键词: 番茄红素, 急性肝损伤, 内质网应激

Abstract:

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 78kda (GRP78), activating trnsfection factor-6 (ATF-6), inositol requiring enzyme (p-IRE-1α), eukaryotic initiation factor-2α (p-eIF-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 PI3K/Akt signaling pathway.

Key words: lycopene, acute liver injury, endoplasmic reticulum stress

中图分类号:

R965.2

廖笑玲，吴亮，林宗泽，叶剑. 番茄红素抑制内质网应激从而减轻CCl₄诱导的小鼠急性肝损伤[J]. 中国临床药理学与治疗学, 2018, 23(7): 770-775.

LIAO Xiaoling，WU Liang，LIN Zongze，YE Jian. Lycopene protects against CCl₄-induced acute hepatic injury via inhibiting endoplasmic reticulum stress[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 770-775.

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番茄红素抑制内质网应激从而减轻CCl₄诱导的小鼠急性肝损伤

Lycopene protects against CCl₄-induced acute hepatic injury via inhibiting endoplasmic reticulum stress

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