山西医科大学公共卫生学院营养与食品卫生学教研室;山西白求恩医院(山西医学科学院,同济山西医院),山西医科大学第三医院;华中科技大学同济医学院附属同济医院;山西医科大学营养与食品科学研究所;长治市第二人民医院;
目的 评价番茄红素是否可以改善D-半乳糖诱导的肝脏衰老及其相关分子机制。方法 将45只2月龄雌性CD-1小鼠适应性喂养1周后，按随机数字表法分为3组，每组15只，对照组：标准饲料+腹腔注射生理盐水；D-半乳糖组：标准饲料+腹腔注射150 mg/kg D-半乳糖；番茄红素干预组：番茄红素饲料(0.03%番茄红素，均匀混在标准饲料中)+腹腔注射150 mg/kg D-半乳糖，共8周。小鼠衰老相关β-半乳糖苷酶(senescence associated-beta-galactosidase, SA-β-gal)染色及酶联免疫分析(ELISA)试剂盒检测肝脏组织SA-β-gal含量、Western blots检测肝脏组织P21及P53蛋白表达，明显高于对照组，即判定衰老小鼠造模成功。试剂盒测定血清中谷丙转氨酶(glutamate pyruvate transaminase, GPT)、谷草转氨酶(glutamic oxaloacetic transaminase, GOT)、碱性磷酸酶(alkaline phosphatase, ALP)活性，肝脏组织中过氧化氢(H_2O_2)、总抗氧化能力(total antioxidant capacity, T-AOC)和丙二醛(malondialdehyde, MDA)活性；ELISA试剂盒检测小鼠肝脏组织成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)、白细胞介素(interleukin, IL)6、8和10含量；免疫荧光检测肝脏组织活性氧(reactive oxygen species, ROS)水平；免疫组化检测肝脏组织线粒体融合蛋白2(mito-fusion 2,MFN2)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平。透射电子显微镜观察肝脏线粒体形态；Western blots检测线粒体融合蛋白1(mito-fusion 1,MFN1)和线粒体分裂蛋白1(fission 1,FIS1)的表达情况。结果 与对照组相比，D-半乳糖组小鼠肝脏SA-β-gal含量升高(P<0.01),P21及P53蛋白表达水平上调(P<0.01),即衰老小鼠造模成功。同时血清GPT(P<0.05)、GOT(P<0.01)及ALP(P<0.05)活性显著上调；T-AOC活性下调(P<0.05),MDA(P<0.05)和H_2O_2(P<0.01)含量升高以及ROS水平上调；透射电子显微镜观察到D-半乳糖组小鼠肝脏线粒体双层膜结构被破坏且肿胀；FGF21水平下调(P<0.05),线粒体分裂基因FIS1蛋白表达下调(P<0.01),线粒体融合基因MFN1及MFN2蛋白表达上调(P<0.05);肝脏组织中促炎因子TNF-α、IL-6(P<0.01)、IL-8(P<0.05)表达上调，以及抗炎因子IL-10表达下调(P<0.01)。与D-半乳糖组相比，番茄红素干预组小鼠肝脏SA-β-gal含量降低(P<0.01)、P21及P53蛋白表达水平下调(P<0.01);血清中GPT(P<0.05)、GOT(P<0.05)及ALP(P<0.01)活性显著下调；T-AOC活性上调(P<0.01),MDA(P<0.01)和H_2O_2(P<0.01)含量降低以及ROS水平下调；透射电子显微镜观察到番茄红素干预组小鼠肝脏线粒体双层膜结构有所改善；FGF21水平上调(P<0.05),线粒体分裂基因FIS1蛋白表达上调(P<0.01),线粒体融合基因MFN1及MFN2蛋白表达下调(P<0.05);肝脏组织中促炎因子TNF-α、IL-6(P<0.05)、IL-8(P<0.05)表达下调，且抗炎因子IL-10表达上调(P<0.05)。结论 番茄红素可以改善D-半乳糖诱导的肝脏衰老、氧化应激、炎症及肝功能损伤，这可能与其对肝脏FGF21信号的激活以及对线粒体功能的增强相关。
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基本信息:
DOI：10.19813/j.cnki.weishengyanjiu.2025.02.014
中图分类号:R575
引用信息:
[1]沈钰淇,张娟,李璐等.番茄红素通过成纤维细胞生长因子21/线粒体动力介导改善D-半乳糖诱导的CD-1雌性小鼠肝脏衰老[J].卫生研究,2025,54(02):265-272.DOI:10.19813/j.cnki.weishengyanjiu.2025.02.014.
基金信息:
国家自然科学基金青年科学基金项目(No.82103840); 山西省应用基础研究计划青年项目(No.20210302124642); 山西省高等学校科技创新项目(No.2020L0175)