负载槲皮素的间充质干细胞外泌体对小鼠肝纤维化的治疗作用  

Therapeutic effect of quercetin-loaded mesenchymal stem cell-derived exosomes on hepatic fibrosis in mice

作　　者：褚学宏[1] Chu Xuehong(Department of Hepatobiliary and Pancreatic Surgery,Henan Provincial People's Hospital,Zhengzhou 450003.China)

机构地区：[1]河南省人民医院肝胆胰腺外科,郑州450003

出　　处：《中国实用医刊》2024年第1期1-5,共5页Chinese Journal of Practical Medicine

摘　　要：目的探讨负载槲皮素的间充质干细胞外泌体对小鼠肝纤维化的治疗作用。方法实验性研究。于2021年6月选取9只无特定病原体级8周龄雄性C57小鼠(购自郑州大学实验动物中心),以随机数字表法分为正常对照组、模型组和负载槲皮素的外泌体治疗组(以下简称治疗组),每组3只。模型组和治疗组通过饲喂低蛋氨酸低胆碱高脂饲料8周构建小鼠肝纤维化模型,其中治疗组于第6周开始每周通过尾静脉注射负载槲皮素的间充质干细胞外泌体进行治疗。第8周时对三组小鼠进行肝组织病理学检查(肝脏纤维化程度根据Ishak评分系统判定)、肝功能检测[天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)和碱性磷酸酶(ALP)],通过免疫组织化学法检测纤维化标志物α-平滑肌肌动蛋白(α-SMA)和Ⅰ型胶原蛋白(collaⅠ)在各组肝脏组织中的表达。结果肝组织切片苏木精-伊红染色和Masson染色结果显示,正常对照组肝小叶结构完整,肝细胞围绕中央静脉排列整齐,形态正常;模型组肝小叶结构紊乱,脂肪变性,局灶性溶解性坏死,门管区纤维增生;治疗组结缔组织增生较模型组得到明显改善。模型组肝纤维化Ishak评分[(3.40±0.49)分]高于正常对照组[(0.00±0.00)分],治疗组肝纤维化Ishak评分[(2.60±0.49)分]低于模型组(P<0.05)。模型组血清AST、ALT和ALP水平均高于正常对照组,治疗组血清AST、ALT和ALP水平低于模型组(P<0.05)。免疫组织化学法检测结果显示,模型组呈现大范围α-SMA和collaⅠ阳性表达,治疗组α-SMA和collaⅠ的表达面积较模型组明显减少。结论负载槲皮素的间充质干细胞外泌体有缓解小鼠肝纤维化的作用。Objective To investigate the therapeutic effect of quercetin-loaded mesenchymal stem cell-derived exosomes on hepatic fibrosis in mice.Methods This experimental study,conducted in June 2021,involved nine specific pathogen free 8-week-old male C57 mice(purchased from the Experimental Animal Center of Zhengzhou University).And they were divided into normal control group,model group and quercetin-loaded exosome treatment group(referred to as the treatment group)using a random number table method,with 3 mice in each group.The model group and the treatment group were subjected to an 8-week regimen of a high-fat diet with low methionine and low choline to induce liver fibrosis.Additionally,the treatment group received weekly intravenous administrations of quercetin-loaded mesenchymal stem cell-derived exosomes via the tail vein starting from the 6th week.At the 8th week,liver histopathology examination(evaluation of the degree of liver fibrosis by Ishak scoring system)and liver function tests,including aspartate transaminase(AST),alanine transaminase(ALT)and alkaline phosphatase(ALP),were performed on all three groups of mice.The expression levels of collagenⅠ(collaⅠ)andα-smooth muscle actin(α-SMA),markers of fibrosis,in the liver tissues of each group were detected by immunohistochemistry at the 8th week.Results Hematoxylin-eosin staining and Masson staining of liver tissue sections revealed that the normal control group exhibited intact liver lobule structure,with orderly arranged liver cells around the central vein,displaying normal morphology.The model group manifested disrupted liver lobular structure,steatosis,focal lytic necrosis and portal fibroplasia.The treatment group exhibited a significant amelioration in connective tissue proliferation compared with the model group.The Ishak score for liver fibrosis in the model group(3.40±0.49)was higher than that in the normal control group(0.00±0.00),while the Ishak score for liver fibrosis in the treatment group(2.60±0.49)was lower than that in the model grou

关 键 词：槲皮素 间充质干细胞 外泌体 肝纤维化 

分 类 号：R285.5[医药卫生—中药学]