大黄酸对非酒精性脂肪性肝炎小鼠M1/M2型巨噬细胞极化平衡的影响  

Study on effect of rhein on M1/M2 macrophage balance in nonalcoholic steatohepatitis mice

作　　者：张文基 王志斌[1] 李军祥[1] 毛堂友 谢春娥[1] 韩海啸[1] 袁亚利 卢心毓 王木源 王建芳[1] ZHANG Wenji;WANG Zhibin;LI Junxiang;MAO Tangyou;XIE Chune;HAN Haixiao;YUAN Yali;LU Xinyu;WANG Muyuan;WANG Jianfang(Dongfang Hospital,Beijing University of Chinese Medicine,Beijing 100078,China)

机构地区：[1]北京中医药大学东方医院消化科,100078

出　　处：《环球中医药》2023年第12期2451-2457,共7页Global Traditional Chinese Medicine

基　　金：国家自然科学基金(82074344);中华中医药学会(2022-2024年度)青年人才托举工程项目(CACM-2022-QNRC2-A02)。

摘　　要：目的探讨大黄酸对非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)小鼠M1/M2型巨噬细胞极化平衡的影响,为中医药治疗NASH提供理论依据。方法将健康SPF级雄性C57BL/6小鼠随机分为空白组、模型组、大黄酸低剂量组和大黄酸高剂量组。模型组、大黄酸低剂量组、大黄酸高剂量组自由食用高脂饲料10周,建立NASH模型,空白组予以普通饲料作为对照。造模成功后,大黄酸低剂量组和大黄酸高剂量组分别予相应浓度药物灌胃4周,空白组和模型组予等量的蒸馏水灌胃。比较各组小鼠体质量、肝组织形态及病理学表现,通过流式细胞术检测小鼠脾脏M1/M2型巨噬细胞水平,实时荧光定量逆转录PCR法检测肝脏组织中细胞因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)mRNA和白细胞介素-10(interleukin-10,IL-10)mRNA的表达。结果与空白组相比,模型组小鼠体质量明显升高(P<0.01),经4周药物治疗后,大黄酸低剂量组的体质量较模型组低(P<0.05),高剂量组体质量明显减轻(P<0.01);模型组肝脏大而软,呈黄色,肝组织空泡样变性、脂肪样变性及炎性细胞浸润,大黄酸各剂量组肝脏形态及病理改变均有所减轻。机制方面,与空白组相比,模型组F4/80+CD16/32+巨噬细胞(M1型)及其细胞因子TNF-αmRNA水平明显升高(P<0.01),F4/80+CD206+巨噬细胞(M2型)及其细胞因子IL-10 mRNA水平略有升高,但无统计学差异。经过药物干预后,各剂量组M1型巨噬细胞及TNF-αmRNA水平明显降低(P<0.05),而M2型巨噬细胞及IL-10 mRNA水平明显升高(P<0.01,P<0.05)。结论大黄酸可以明显改善NASH小鼠肝细胞脂肪变性和炎症细胞浸润,其作用机制与恢复M1/M2型巨噬细胞平衡有关。Objective To explore the effect of rhein on M1/M2 macrophage balance in mice with nonalcoholic steatohepatitis(NASH),providing a theoretical basis for traditional Chinese medicine treatment of NASH.Methods Healthy SPF male C57BL/6 mice were randomly divided into control group,model group,low dose rhein group and high dose rhein group.The model group,the low dose rhein group and the high dose rhein group consumed a high-fat diet ad libitum for 10 weeks to establish the NASH model,and the control group received regular feed.After successful modeling,the low dose rhein group and the high dose rhein group were given the corresponding concentration of drugs by gavage for 4 weeks,while the control group and the model group were given equal amounts of distilled water by gavage.The body weight of mice,morphological and pathological changes in the liver tissue in each group were compared.The levels of M1/M2 macrophages in spleens were determined by flow cytometry.The expression of tumor necrosis factor-α(TNF-α)mRNA and interleukin-10(IL-10)mRNA in liver tissues were determined by quantitative reverse transcription PCR.Results Mice in the model group had significantly higher body weight compared with the control group(P<0.01).After 4 weeks of drug treatment,weight was decreased in the low dose rhein group compared with the model group(P<0.05)and was significantly decreased in the high dose rhein group(P<0.01).The liver of the model group was large and soft,showing a yellow color,with vacuolar degeneration,adipose degeneration,and inflammatory cell infiltration in the liver tissue.The liver morphological and pathological changes in each dose group of rhein were alleviated.In terms of mechanism,compared with the control group,the model group showed a significant increase in the level of F4/80+CD16/32+macrophages(M1)and their cytokine TNF-αmRNA(P<0.01),while the level of F4/80+CD206+macrophages(M2)and their cytokine IL-10 mRNA were slightly increased without statistical difference.After drug intervention,the level of M1 an

关 键 词：非酒精性脂肪性肝炎 大黄酸 巨噬细胞极化 炎症 机制研究 免疫学治疗 

分 类 号：R285.5[医药卫生—中药学]