摘要
主要通过观察胡柚皮黄酮(PTFC)对非酒精性脂肪性肝炎(NASH)小鼠Th17/Treg平衡的调节作用,探讨其干预NASH进展的免疫机制。以高脂饮食16周建立C57BL/6小鼠NASH模型,在造模第7周起分别预以25,50,100 mg·kg-1·d-1的PTFC灌胃干预10周,生化法检测血清TG,CHOL,ALT,AST水平,HE染色观察肝组织病理学变化;Real-time PCR检测肝组织RORγt和Foxp3 mRNA表达;流式CBA法检测血清IL-17,IL-6,IL-10,IL-4水平。研究发现,模型组小鼠血清CHOL,ALT,AST水平较正常组升高,TG水平下降;肝组织RORγt mRNA表达增强,Foxp3 mRNA表达下降,RORγt/Foxp3比值下降;血清IL-17,IL-6水平升高,IL-10,IL-4水平降低;PTFC干预后能明显减轻NASH小鼠肝组织炎症程度,改善肝功能,同时能够促进肝组织Foxp3 mRNA的表达而抑制RORγt mRNA表达,有效降低促炎因子IL-17和IL-6的水平而提高抑制性细胞因子IL-10和IL-4的水平。研究表明,高脂饮食诱导的NASH小鼠存在着Th17/Treg的免疫失衡,PTFC能通过调节Th17/Treg的平衡而缓解NASH的炎症反应,防止其进展。
This study aimed to investigate the involved immunologic mechanism of pure total flavonoids from Citrus (PTFC) on the development of non-alcoholic steatohepatitis (NASH). C57BL/6 mice were fed with high fat diet for 16 weeks to induce the NASH model, and from the 7th week three dosages(25,50 and 100 mg· kg-1· d-1) of PTFC were administrated intragastric for 10 weeks respectively. Serum TG, CHOL, ALT, AST were determined by biochemical assay, histopathological changes of the liver tissue were observed by HE staining, expression of RORTt and Foxp3 mRNA of the liver tissue was detected by Real-time PCR, and serum IL-17, IL-6, IL-10 and IL-4 were determined by Cytometric Beads Array. As a result, we find that after the administration of PTFC, the in- flammation of the liver tissue of NASH mice was attenuated, liver function was improved, and the expression of RORTt mRNA was higher in the liver tissue while which was lower of Foxp3 mRNA, the level of proinflammatory cytokines IL-17 and IL-6 decreased and the level of suppressive cytokines IL-10 and IL-4 increased. These data show that PTFC protects the development of NASH through reg-ulating the Thl7/Treg balance and attenuating inflammation.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2015年第13期2644-2648,共5页
China Journal of Chinese Materia Medica
基金
浙江省自然科学基金项目(LY13H290011)
浙江省中医药科学研究基金项目(2013ZA047)