摘要
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-1β、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。
Objective To observe the effect of geniposide on rats with non-alcoholic steatohepatitis(NASH), and to study its mechanism for preventing and treating NASH based on the gut-liver axis. Methods Totally 35 rats were divided into 5 groups, i.e., the normal group, the model group, the geniposide group, Pioglitazone Hydrochloride Tablets group, and Bifidobacterium group by random digit table, 7 in each group. NASH rat model was established in 28 rats except those in the normal group using high fat diet for 16 weeks. Medication was started from the 9 th week of modeling, and the treatment lasted for 8 weeks. Blood was collected from abdominal aorta at the end of 16 weeks. The level of triglyceride(TG) was detected by biochemical method. The pathological changes of liver and intestinal tissues were observed by HE staining. The expression levels of inflammatory factors such as IL-1β, IL-6, and tumor necrosis factor-α(TNF-α) in liver tissues were detected by ELISA. End point chromogenic assay was used to detect the lipopolysaccharide(LPS) levels in plasma. Results Compared with the normal group, typical histological features of NASH occurred in the liver tissue of rats in the model group. After intervened with geniposide, steatosis of liver cells, infiltration of inflammation were attenuated more obviously, as compared with the model group. Compared with the normal group, little amount of intestinal epithelial cells desquamated and intestinal mucosal mechanical barrier was impaired in the model group. After intervened with geniposide, ileum mucosal structure was intact with no obvious desquamated intestinal epithelial cells seen. Compared with the normal group, the levels of fat weight, liver wet weight, liver index, liver TG content, plasma LPS, the levels of inflammatory factors such as IL-1β, IL-6, TNF-α were significantly elevated to various degrees in the model group(P<0.01). After treatment, the levels of fat weight, liver wet weight, liver index, liver TG content, plasma LPS, the levels of inflammatory factors such as IL-1β, IL-6, and TNF-α decreased to different degrees(P<0.05, P<0.01). Conclusions Geniposide significantly improved the intestinal mucosal structure, maintained the integrity of intestinal mucosal barrier, significantly reduced plasma LPS level, significantly decreased the expressions of IL-1β, IL-6, and TNF-α in liver tissue of NASH rats. It suggested that the mechanism of geniposide for the treatment of NASH should be related to regulating gut-liver axis, improving intestinal mucosal barrier, reducing the production of endogenous LPS, and reducing the expressions of inflammatory factors.
作者
许玲夏
郭蓁萤
周志佳
梁惠卿
许诗霖
李新月
陈雨昌
焦子路
邵高眩
赖鹏华
张绍良
李晓英
陈少东
XU Ling-xia;GUO Zhen-ying;ZHOU Zhi-jia;LIANG Hui-qing;XU Shi-lin;LI Xin-yue;CHEN Yu-chang;JIAO Zi-lu;SHAO Gao-xuan;LAI Peng-hua;ZHANG Shao-liang;LI Xiao-ying;CHEN Shao-dong(Department of Traditiona/ Chinese Medicine,School of Medicine,Xiamen University,Fujian (361102);Center for Liver Disease,Xiamen Hospital of Traditional Chinese Medicine,Fujian (361009))
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2019年第10期1240-1244,共5页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金资助项目(No.81673660)
2017、2018厦门大学大学生创新创业训练课题(No.2017X0547
No.201810384230)
关键词
栀子苷
非酒精性脂肪性肝炎
肠肝轴
geniposide
non-alcoholic steatohepatitis
gut-liver axis
