Th17/Treg免疫平衡在非酒精性脂肪性肝炎防治中的作用及降脂颗粒的调控机制

Role of Th17/Treg immune balance in the prevention and treatment of nonalcoholic steatohepatitis and the regulatory mechanism of Jiangzhi Granules

目的:探究中药复方降脂颗粒对非酒精性脂肪性肝炎(NASH)患者及模式动物Th17/Treg免疫平衡的影响及潜在机制。方法:对NASH患者进行降脂颗粒干预,检测治疗前后血清IL-17A、IL-6和TGF-β水平及Treg细胞比例。C57BL/6N小鼠分为对照组(CON)、模型组(NASH)和降脂颗粒组(JZG),以MCD饮食诱导NASH模型并予降脂颗粒干预;检测小鼠体质量、肝重、肝/体比、血清酶学指标和肝脂含量,结合肝组织病理染色及NAS评分,评估降脂颗粒对NASH小鼠表型的影响;通过PCR法、流式细胞术、ELISA及免疫组化等方法探索降脂颗粒调控Th17/Treg免疫平衡的机制。结果:降脂颗粒可下调NASH患者血清IL-17A和IL-6水平,上调外周血Treg细胞比例。降脂颗粒可降低NASH小鼠血清ALT和肝脏TG水平,减轻肝脏脂肪变性和炎症浸润,抑制肝脏巨噬细胞浸润和TNF-α、IL-1β含量。降脂颗粒可降低NASH小鼠肝脏IL-6含量和STAT3磷酸化水平,上调SOCS2水平。结论:降脂颗粒可有效改善NASH,其机制可能通过抑制IL-6/STAT3信号通路进而调控Th17/Treg免疫平衡而实现。

Objective:To explore the effects of Jiangzhi Granules(JZG)on Th17/Treg immune balance in non-alcoholic steatohepatitis(NASH)patients and model animals as well as the potential mechanisms.Methods:After intervention of JZG,the serum IL-17A,IL-6,and TGF-βcontent and the percentage of Treg of NASH patients were detected.The C57BL/6N mice were divided into control group(CON),model group(NASH)and JZG group(JZG).The NASH model was induced by MCD diet and JZG was given simultaneously.The bodyweight,liver weight,serum enzymology and liver fat content of the mice were measured,and the pathological changes of liver tissues(H&E and oil red O staining)and NAS scores were evaluated to clarify the effect of JZG on NASH mice.The mechanism behinds JZG regulating Th17/Treg immune balance was explored by PCR,flow cytometry,ELISA and immunohistochemistry.Results:JZG downregulated the levels of IL-17A and IL-6 in NASH patients,and upregulated the proportion of Treg.In NASH mice,JZG reduced the serum ALT and liver TG levels,improved steatosis and inflammatory infiltration,and decreased liver macrophage infiltration as well as TNF-αand IL-1βcontent.JZG inhibited the expression of IL-6 and the phosphorylation level of STAT3 in the liver of NASH mice via upregulating SOCS2.Conclusion:JZG can effectively improve NASH possibly by inhibiting IL-6/STAT3 signaling pathway,which regulates Th17/Treg immune balance.