首页|茵陈苓桂术甘汤对非酒精性脂肪性肝病Th17/Treg细胞免疫平衡的影响

茵陈苓桂术甘汤对非酒精性脂肪性肝病Th17/Treg细胞免疫平衡的影响

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目的:探讨茵陈苓桂术甘汤对非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)小鼠Th17/Treg细胞免疫平衡的调控作用,为其临床应用提供依据。方法:将SPF级雄性C57BL/6小鼠随机分为空白组、模型组、茵陈苓桂术甘汤低剂量组、茵陈苓桂术甘汤中剂量组和茵陈苓桂术甘汤高剂量组。采用高脂饲料诱导NAFLD小鼠模型,造模成功后药物组分别予相应浓度药物灌胃,空白组和模型组予等量的蒸馏水灌胃,1次/d,共4周,观察不同方式治疗后小鼠体重及肝组织病理学变化,通过流式细胞术检测小鼠肠系膜淋巴结辅助性T细胞17(Th17细胞)、调节性T细胞(Treg细胞)水平,以及Th17/Treg细胞比率;并通过RT-qPCR检测二者相关细胞因子IL-17、IL-10的mRNA表达。结果:与空白组比较,模型组小鼠体重明显增加(P<0。01),肝细胞出现空泡样变性及脂肪变性,炎性细胞浸润明显;经治疗4周后,茵陈苓桂术甘汤各剂量组小鼠体重明显降低(P<0。05,P<0。01);肝组织空泡样变性、脂肪样变性及炎性细胞浸润均明显减轻。机制方面,与空白组比较,模型组小鼠肠系膜淋巴结Th17占比显著升高(P<0。01),其相关细胞因子IL-17的mRNA表达水平显著升高(P<0。05);而Treg细胞占比显著降低(P<0。05),其相关细胞因子IL-10的mRNA表达水平降低(P<0。01),Th17/Treg细胞比率显著升高,差异有统计学意义(P<0。01)。茵陈苓桂术甘汤组与模型组比较,小鼠肠系膜淋巴结Th17占比显著降低(P<0。01),其相关细胞因子IL-17的mRNA水平显著降低(P<0。01);而Treg细胞占比显著升高(P<0。01),其相关细胞因子IL-10的mRNA表达水平显著升高(P<0。01);Th17/Treg显著降低,差异有统计学意义(P<0。01)。结论:茵陈苓桂术甘汤可以显著改善NAFLD小鼠肝细胞的脂肪变性及炎性细胞浸润,其作用机制与调节Th17/Treg细胞免疫平衡有关。
Study on the mechanism of Yinchen Linggui Zhugan Decoction regulating Th17/Treg immune balance in nonalcoholic fatty liver disease mice
Objective:To investigate the modulating effect of Yinchen Linggui Zhugan Decoction(YLZD)on Th17/Treg immune balance in nonalcoholic fatty liver disease(NAFLD)mice,providing a scientific basis for its treatment of NAFLD.Methods:SPF-grade male C57BL/6 mice were randomly divided into a control group,mod-el group,low-dose YLZD group,medium-dose YLZD group,and high-dose YLZD group,with five mice in each group.The NAFLD mouse model was induced with high-fat feed.After successful modeling,the drug group was given corresponding concentrations of drugs by gavage.In contrast,the control and model groups were given equal amounts of distilled water by gavage once a day for four weeks.The pathological changes in the liver tissue of mice after different drug treatments were observed.Flow cytometry was used to detect the helper T cell 17(CD3+CD4+IL-17+Th17 cells),regulatory T cell(CD3+CD4+Foxp3+Treg cells)levels,Th17/Treg in mesenteric lymph nodes.RT-qPCR detected liver IL-17 and IL-10.Results:Compared with the control group,the weight of the model group mice significantly increased(P<0.01).Hepatocyte ballooning degeneration,steatosis and in-flammatory cell infiltration were obvious.After four weeks of drug treatment,compared with the model group,the weight of mice in each dose group of YLZD significantly decreased(P<0.05,P<0.01).Ballooning degenera-tion,lipoid degeneration,and inflammatory cell infiltration in liver tissue were significantly reduced.In terms of mechanism,the proportion of Th17 in mouse mesenteric lymph nodes of the model group mice significantly re-duced(P<0.01),and the mRNA expression levels of IL-17 significantly increased(P<0.05),the Th17/Treg significantly increased(P<0.01),while the proportion of Treg cells significantly decreased(P<0.05),the mR-NA levels of IL-10 decreased(P<0.01).However,the proportion of Th17 in mouse mesenteric lymph nodes of YLZD significantly decreased(P<0.01)and the mRNA levels of IL-17 were significantly reduced(P<0.01);while the proportion of Treg cells significantly increased(P<0.01)and the mRNA expression level of IL-10 in-creased(P<0.01),the Th17/Treg significantly decreased(P<0.01).Conclusion:Yinchen Linggui Zhugan De-coction can significantly alleviate the steatosis and inflammatory cell infiltration of NAFLD mice induced by a high-fat diet,which may exert therapeutic effects by regulating Th17/Treg cell immune balance.

nonalcoholic fatty liver diseaseYinchen Linggui Zhugan DecoctionTh17/Treg cell immune balance

袁亚利、毛堂友、韩海啸、董瑾操、卢心毓、王木源、邢韵淇、张文基、谢春娥

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北京中医药大学东方医院脾胃肝胆科(北京,100029)

秦皇岛市中医医院脾胃肝胆科

深圳市宝安中医院脾胃病科

非酒精性脂肪性肝病 茵陈苓桂术甘汤 Th17/Treg免疫平衡

国家自然科学基金资助项目中华中医药学会青年人才托举工程项目

82074344CACM-2022-QNRC2-A02

2024

中国中西医结合消化杂志
华中科技大学同济医学院,中国中西医结合学会消化系统疾病专业委员会,中华中医药学会脾胃病专业委员会

中国中西医结合消化杂志

CSTPCD
影响因子:1.363
ISSN:1671-038X
年,卷(期):2024.32(2)
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