鹿茸干细胞来源外泌体调控NF-κB信号通路预防小鼠酒精性肝损伤  

Deer antler stem cell-derived exosomes prevent alcoholic liver injury via modulating nuclear factor kappa B signaling pathway in mice

作　　者：王东旭 任晶 李吉萍 王玉俗 胡鹏飞 张国坤 李春义 Wang Dongxu;Ren Jing;Li Jiping;Wang Yusu;Hu Pengfei;Zhang Guokun;Li Chunyi(Changchun Sci-Tech University,Changchun 130116,Jilin Province,China;College of Chinese Medicinal Materials,Jilin Agricultural University,Changchun 130118,Jilin Province,China)

机构地区：[1]长春科技学院,吉林省长春市130116 [2]吉林农业大学中药材学院,吉林省长春市130118

出　　处：《中国组织工程研究》2023年第24期3824-3830,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(U20A20403),项目负责人:李春义。

摘　　要：背景:过度的酒精摄入会导致诸多的肝脏疾病,然而目前尚无有效的防治药物。前期研究发现鹿茸干细胞能够显著改善肝纤维化,推测其治疗作用可能是通过旁分泌效应产生的。目的:研究鹿茸干细胞的主要旁分泌物质——外泌体对小鼠急性肝损伤的预防作用及其机制。方法:40只C57BL6小鼠随机分为对照组、模型组、骨髓间充质干细胞外泌体预防组、鹿茸干细胞外泌体预防组,每组10只。2个外泌体预防组连续7 d给予相应外泌体进行干预,模型组给予PBS干预,然后给予体积分数为50%的酒精(15 mL/kg)灌胃1次建立急性酒精性肝损伤模型。灌胃后24 h,计算肝指数、检测肝损伤及氧化还原指标、评价肝组织病理病变、检测炎症因子和NF-κB信号通路相关基因的表达水平。结果与结论:(1)鹿茸干细胞来源外泌体显著减轻了肝损伤的程度,包括改善体质量、降低血清中谷丙转氨酶和谷草转氨酶水平、改善肝组织病理病变、促进肝实质细胞增殖分裂以及提高抗氧化水平(谷胱甘肽过氧化物酶和超氧化物歧化酶水平升高,丙二醛水平降低),且效果强于骨髓间充质干细胞来源外泌体;(2)进一步研究发现,鹿茸干细胞来源外泌体显著降低了肝组织中白细胞介素1β、白细胞介素6和肿瘤坏死因子α的mRNA表达水平,以及NF-κB信号通路相关基因(p65、p-p65、IKB和p-IKB)的蛋白表达水平;(3)这说明鹿茸干细胞来源外泌体能够起到保护肝脏的作用,减轻酒精所造成的肝损伤,其作用的发挥可能是通过靶向抑制NF-κB信号通路实现的。BACKGROUND:Excessive alcohol intake can lead to many liver diseases,but there is currently no effective drug to prevent it.Previous studies have found that antler stem cells can significantly improve liver fibrosis,and it is speculated that the therapeutic effect may be achieved through paracrine effects.OBJECTIVE:To investigate the preventive effects of antler stem cell-derived exosomes on acute liver injury in mice and its underlying mechanism.METHODS:Forty C57BL6 mice were randomly divided into the control,model,bone marrow mesenchymal stem cell-derived exosome prevention,and antler stem cell-derived exosome prevention groups(n=10).The prevention groups were intervened with exosomes for 7 consecutive days,and the model group was intervened with PBS,followed by 50%alcohol(15 mL/kg)gavage for modeling of acute alcoholic liver injury.At 24 hours after gavage,liver indexes were calculated;liver injury and redox indexes were detected;the pathological lesions of liver tissues were evaluated and the expression levels of inflammatory factors and nuclear factor-κB signaling pathway-related genes were detected.RESULTS AND CONCLUSION:(1)Antler stem cell-derived exosome significantly reduced liver injury,including increasing body weight,decreasing alanine aminotransferase and aspartate aminotransferase levels in serum,improving liver histopathological lesions,promoting proliferation and division of the hepatocytes and increasing antioxidant levels(increasing glutathione peroxidase and superoxide dismutase levels and decreasing malondialdehyde levels).The effects were stronger than those of bone marrow mesenchymal stem cell-derived exosomes.(2)Further studies revealed that antler stem cell-derived exosome significantly reduced the mRNA expression levels of relevant inflammatory factors(interleukin-1β,interleukin-6 and tumor necrosis factorα)and protein expression levels of nuclear factor-κB signaling pathway-related genes(p65,p-p65,IKB and p-IKB)in liver tissues.(3)Overall,our results suggest that antler stem cell-deri

关 键 词：鹿茸干细胞 外泌体 酒精性肝损伤 炎症 NF-ΚB信号通路 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R575