Objective : Chlorogenic acid and geniposide (CG) are derived from traditional Chinese medicine, Yinchenhao Recipe (QCHR), and can improve the clinical efficacy of NASH patients. This study investigated the effects of CG on NASH and expounded its Potential mechanism of action through the LPS-TLR4 pathway and microbiota. Methods: Rats were randomized into Control (C), Model (M), Chlorogenic Acid and Geniposide (CG), Pioglitazone (PH) and Bifico (B) groups. After an 8-week high-fat diet (HFD), CG, PH and B oral treatment were initiated and carried out for a further 8 weeks. The stool samples were used in a16S rDNA V4 highly variable region measurement method in order to regulate the role of CG in gut microbiota. The concentrations of triglyceride (TG), cholesterol (CHO), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in LPS were detected by the corresponding methods. Results : Observations were made that CG significantly improved the pathology of the liver and terminal ileum tissue. The accumulation of TG and the content of inflammatory cytokines in the liver were significantly decreased and the abundance of Proteobacteria was significantly down-regulated. The expression of TLR4, AP-1, MyD88, and phosphorylated NF-κB p65 were significantly decreased. All the findings above indicated that CG was highly effective in improving the composition of gut microbiota, decreasing the production of endogenous LPS, and reducing the secretion of inflammatory cytokines through the gut-liver axis. Conclusion : CG can regulate the abundance and diversity of the intestinal microbial community and improve liver inflammation and steatosis in NASH rats by reducing LPS-TLR4-mediated inflammation.

目的:基于内源性大麻素研究皂术抗纤方对肝纤维化大鼠的药理效应及其作用机制.方法:按照随机数字表法将40只Wistar雄性大鼠随机分为正常组、模型组、皂术抗纤方组和安络化纤丸组,每组10只.模型组、皂术抗纤方组和安络化纤丸组给予四氯化碳(CCl4)腹腔注射8周,复制肝纤维化模型.第5～8周,皂术抗纤方组、安络化纤丸组分别给予皂术抗纤方(16.1g/kg)、安络化纤丸(30g/kg)治疗.检测各组大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平,肝组织羟脯氨酸(Hyp)、N-花生四烯酸氨基乙醇(AEA)、2-花生四烯酸甘油(2-AG)及内源性大麻素水解酶脂肪酰胺水解酶(FAAH)、单酰基甘油酯酶(MGL) mRNA表达量变化.结果:与正常组比较,模型组大鼠肝组织出现明显肝纤维化,血清ALT、AST水平及肝组织Hyp、AEA、2-AG含量显著升高(P＜0.01),FAAH、MGL mRNA表达显著降低(P＜0.01).与模型组比较,皂术抗纤方组、安络化纤丸组血清ALT、AST水平及肝组织Hyp含量均显著降低(P＜0.01),皂术抗纤方组肝组织大麻素AEA、2-AG含量显著降低(P＜0.01),FAAH、MGL mRNA表达显著升高(P＜0.01).结论:皂术抗纤方治疗肝纤维化效果显著,其作用机制与调节内源性大麻素有关.

目的 研究皂术茵陈方对非酒精性脂肪性肝炎大鼠的药理效应及对内源性大麻素的作用机制.方法 30只Wistar雄性大鼠随机分为正常组、模型组和治疗组,每组10只.造模12周期间,正常组给予普通饲料喂养,模型组和治疗组给予高脂饲料以复制非酒精性脂肪性肝炎模型.从第7周开始,治疗组给予皂术茵陈方灌胃治疗6周.检测大鼠血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)活性,肝组织甘油三酯(TG)、总胆固醇(TC);HE染色法观察大鼠肝组织的病理变化;采用高效液相色谱-质谱联用法(LC/MS)检测肝组织2-花生四烯酸甘油(2-AG)含量;通过Real-time PCR法检测大鼠肝组织脂肪酰胺水解酶(FAAH)和单酰基甘油酯酶(MGL) mRNA表达水平.结果 与正常组比较,模型组大鼠肝组织内出现明显脂肪沉积和炎症损伤,血清ALT、AST活性明显升高(P＜0.01),肝组织TG、TC含量升高(P＜0.01);肝组织大麻素2-AG含量显著升高(P＜0.01),FAAH、MGL mRNA表达降低(P＜0.01).治疗组与模型组比较,治疗6周后血清ALT、AST活性、肝组织TG、TC、大麻素2-AG含量明显降低(P＜0.05),FAAH、MGL mRNA表达升高(P＜0.01).结论 皂术茵陈方对非酒精性脂肪性肝炎具有良好的治疗作用,其作用机制与抑制内源性大麻素密切相关.

目的 观察栀子苷对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)大鼠的影响,并基于肠肝轴探讨栀子苷防治NASH的作用机制.方法 将35只大鼠按随机数字表法分为5组,每组7只.即正常组、模型组、栀子苷组、盐酸吡格列酮组及培菲康组.除正常组外,其余28只大鼠采用高脂饮食16周建立大鼠NASH模型,在造模第9周开始给药,共治疗8周.第16周末经腹主动脉取血,生化法检测肝组织甘油三酯(TG)水平,苏木精-伊红(HE)染色观察肝组织、肠组织病理学变化.ELISA法检测肝组织白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)等炎症因子的表达水平.终点显色法检测血浆内毒素(LPS)含量.结果 与正常组比较,模型组大鼠的肝组织显示出典型的NASH组织学特征,经栀子苷干预后,肝细胞脂肪变性、炎症浸润较模型组减轻.与正常组比较,模型组大鼠肠上皮细胞少量脱落,肠黏膜机械屏障受损.经栀子苷干预后,回肠黏膜结构完整,未见明显肠上皮细胞脱落.与正常组比较,模型组大鼠脂肪重量、肝湿重、肝指数、肝脏TG含量、血浆LPS水平、肝组织IL-1β、IL-6、TNF-α等炎症因子水平均有不同程度增高(P＜0.01).经干预后,栀子苷组大鼠脂肪重量、肝湿重、肝指数、肝脏TG含量、血浆LPS水平、肝组织IL-1β、IL-6、TNF-α等炎症因子水平均较模型组有不同程度的下降(P＜0.05,P＜0.01).结论 栀子苷能明显改善大鼠肠黏膜组织结构,保持肠黏膜屏障的完整性,显著降低血浆LPS水平,显著降低NASH大鼠肝组织IL-1 β、IL-6、TNF-α等炎症因子的表达.提示栀子苷治疗NASH的作用机制与调节肠肝轴、改善肠黏膜屏障、减少内源性LPS产生、降低炎症因子表达有关.

目的:观察慢性乙型肝炎(CHB)患者肝组织乙型肝炎核心抗原(HBcAg)表达模式与中医证型及肝组织炎症、纤维化等指标的关系并进一步探讨相应的机制.方法:选择CHB患者556例,均进行中医辨证分型及肝组织活检,测定肝组织HBcAg表达模式、炎症、纤维化程度及ALT、AST、HBV DNA水平.结果:①556例患者按中医辨证标准分为6组:瘀血阻络证44例、肝肾阴虚证42例、肝郁气滞证48例、肝郁脾虚证282例、湿热蕴结证140例、脾肾阳虚证0例;按HBcAg表达模式分HBcAg阴性组42例、胞浆型HBcAg组186例、胞浆优势型HBcAg组290例、浆核各半型HBcAg组38例.②经Spearman秩相关分析,肝组织HBcAg表达模式与肝组织炎症活动度、纤维化程度均呈负相关;经Fisher确切概率检验,肝组织HBcAg表达模式与中医证型分布具有相关性.结论:肝组织HBcAg表达模式与中医证型、肝组织炎症、纤维化程度均有相关性;HBcAg阴性组、胞浆型HBcAg组及肝郁脾虚证、湿热蕴结证多处于慢性乙型肝炎活动期,正气未伤,免疫功能较强,为抗病毒治疗的较佳时机.