内质网应激参与蛋氨酸-胆碱缺乏饮食诱导的小鼠非酒精性脂肪肝的形成

发布时间：2019-01-24 10:19

【摘要】：【目的】探讨内质网应激在蛋氨酸-胆碱缺乏膳食(MCD)诱导的非酒精性脂肪肝炎症以及纤维化形成中的作用。【方法】8周龄C57BL/6雄性小鼠80只,随机分为2个组,8个亚组(n=10),亚组1~4组给予普通膳食,5~8组给予MCD喂养。并各在第2、4、6、8周处死普通膳食组和MCD组各一组。组织病理染色方法和NAS评分评估小鼠纤维化和炎症程度,内质网应激指标磷酸化蛋白激酶R样内质网R激酶(PERK)、磷酸化真核细胞起始因子2α(eIF2α)、CCAAT/增强子结合蛋白同源蛋白(CHOP)采用Western Blot和实时荧光定量PCR(RT-PCR)方法检测。重点分析内质网应激与肝脏炎症以及纤维化形成的关系。【结果】MCD组NAS评分和血清中ALT、AST以及肝组织中TG、TC水平均高于普通膳食组;MCD组pPERK、p-eIF2α、CHOP蛋白表达亦明显高于正常膳食组,而GADD34 mRNA表达显著低于普通膳食组,且随时间推移,MCD组内质网应激逐渐加重;相关分析表明在MCD组中内质网应激相关指标与NAS评分呈显著相关。【结论】在蛋氨酸-胆碱缺乏膳食诱导的小鼠中,小鼠肝脏损伤加重,炎症和纤维化程度加深,而内质网应激确是参与了这个过程。
[Abstract]:[objective] to investigate the role of endoplasmic reticulum stress in the formation of non-alcoholic fatty liver inflammation and fibrosis induced by methionine choline deficiency dietary (MCD). [methods] Eighty 8-week-old C57BL/6 mice were randomly divided into two groups. Eight subgroups (n = 10) were given normal diet, and five or eight groups were fed with MCD. The normal diet group and the MCD group were killed for 8 weeks. Histopathological staining and NAS score were used to evaluate the degree of fibrosis and inflammation in mice, and endoplasmic reticulum stress index phosphorylated protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated eukaryotic initiation factor 2 伪 (eIF2 伪). CCAAT/ enhancer binding protein (CHOP) was detected by Western Blot and real-time quantitative PCR (RT-PCR). The relationship between endoplasmic reticulum stress and hepatic inflammation and fibrosis was analyzed. [results] the NAS score, ALT,AST in serum and TG,TC level in liver tissue in MCD group were higher than those in normal diet group. The expression of pPERK,p-eIF2 伪 and CHOP protein in MCD group was significantly higher than that in normal diet group, while the expression of GADD34 mRNA was significantly lower than that in normal diet group, and the endoplasmic reticulum stress in MCD group increased gradually over time. Correlation analysis showed that endoplasmic reticulum stress was significantly correlated with NAS score in MCD group. [conclusion] in mice induced by methionine choline deficiency diet, liver injury was aggravated, inflammation and fibrosis were aggravated. Endoplasmic reticulum stress is involved in this process.
【作者单位】：广东省膳食营养与健康重点实验室//中山大学公共卫生学院营养学系;
【基金】：广东省科技计划项目(2013B09060013)
【分类号】：R575.5

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