中国中药杂志

2020, v.45(19) 4692-4698

[打印本页] [关闭]
本期目录(Current Issue) | 过刊浏览(Past Issue) | 高级检索(Advanced Search)

鹿仙草多糖通过靶向miR-122a改善酒精性肝病的实验研究
Experimental study on improvement of alcoholic liver disease by polysaccharides from Balanophora henryi through targeting miR-122a

肖莉;何毓敏;彭帆;杨建林;袁成福;
XIAO Li;HE Yu-min;PENG Fan;YANG Jian-lin;YUAN Cheng-fu;Medical College, China Three Gorges University;Hubei Key Laboratory of Tumor Microenvironment and Immunotheraphy, China Three Gorges University;

摘要(Abstract):

研究鹿仙草总多糖(total polysaccharides from Balanophora henryi,TBP)对酒精性肝病(alcoholic liver disease, ALD)的作用,并探究其可能的作用机制。C57BL/6N小鼠随机分为4组,配对饮食对照组,酒精饮食模型组,模型+TBP干预组,TBP对照组。采用Gao-binge法制备慢性ALD小鼠模型,同时用400 mg·kg~(-1) TBP进行干预,喂养6周后留取血清和组织待检测。与饮食对照组相比,模型组小鼠肝组织表现出明显的脂肪样变和炎性细胞的大量浸润,血清谷丙转氨酶(ALT)和谷草转氨酶(AST)水平升高。经过TBP干预后,模型组小鼠肝脏组织病理学变化明显改善,脂质沉积减少,肝细胞排列较为紧密,炎性因子表达水平降低,同时血清ALT和AST的水平降低,说明TBP具有显著改善ALD的作用。对小鼠结肠组织的观察显示,TBP能有效维持ALD小鼠肠道组织结构的完整性,增强紧密连接蛋白occludin的表达和降低miR-122a水平,更重要的是显著降低模型小鼠血清脂多糖(LPS)水平。这一结果表明,TBP可能通过维持和增强肠道屏障功能来发挥对ALD的护肝作用。体外实验发现,TBP能够显著抑制乙醇暴露下Caco-2细胞中miR-122a的表达水平。在Caco-2细胞中过表达miR-122a诱导了对occludin蛋白生成的抑制,而TBP的加入可以显著干预这一作用。这些结果提示,TBP通过增强occludin蛋白表达来维持肠道屏障功能的稳定性,减少肠道LPS进入肝脏进而改善ALD,其潜在机制部分可能是通过抑制miR-122a的表达实现的。
The aim of this paper was to investigate the effect of total polysaccharide from Balanophora henryi(TBP) on alcoholic liver disease(ALD) and explore the possible mechanism. C57 BL/6 N mice were randomly divided into 4 groups: pair-feeding group, alcohol-feeding model group, model+TBP group and TBP drug control group. The Gao-binge method was used to prepare the chronic ALD model, and at the same time, 400 mg·kg~(-1) TBP was given for interventional therapy. After feeding for 6 weeks, the serum, liver and colon tissues were collected for detection. As compared with the pair-feeding group, the model group mice showed obvious fatty degeneration and a large number of infiltration of inflammatory cells in the liver, with increased serum ALT and AST levels. After TBP intervention, histopathological changes in liver tissues were significantly improved, with decreased lipid deposition, closer arrangement of hepatocytes, lower expression level of inflammatory factors, and reduced activity of serum ALT and AST, indicating that TBP had a significant improvement effect on ALD. The observation of colonic tissues in mice showed that TBP effectively maintained the integrity of intestinal tissue structure of mice with ALD, enhanced the expression of tight junction protein occludin and reduced miR-122 a expression level. More importantly, TBP significantly reduced serum lipopolysaccharide(LPS) level in model mice. These results indicated that TBP may improve ALD by maintaining and enhancing intestinal barrier function. In vitro experiments showed that TBP significantly inhibited the expression level of miR-122 a in Caco-2 cells exposed to ethanol. Overexpression of miR-122 a in Caco-2 cells induced the inhibition of occludin protein production, and the addition of TBP significantly interfered with the effect. These results suggested that TBP could improve ALD by maintaining the stability of intestinal barrier function and reducing LPS content into the liver, and the mechanism may be partially related to inhibiting miR-122 a expression.

关键词(KeyWords): 鹿仙草多糖;酒精性肝病;miR-122a;肠-肝轴;肠道屏障
polysaccharide from Balanophora henryi;alcoholic liver disease;miR-122a;gut-liver axis;intestinal barrier

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81903916,81773959);; 湖北省自然科学基金项目(2018CFB644);; 三峡大学湖北肿瘤微环境与免疫治疗重点实验室开放基金项目(2018KZL04)

作者(Author): 肖莉;何毓敏;彭帆;杨建林;袁成福;
XIAO Li;HE Yu-min;PENG Fan;YANG Jian-lin;YUAN Cheng-fu;Medical College, China Three Gorges University;Hubei Key Laboratory of Tumor Microenvironment and Immunotheraphy, China Three Gorges University;

Email:

DOI: 10.19540/j.cnki.cjcmm.20200514.402

参考文献(References):

扩展功能
本文信息
服务与反馈
本文关键词相关文章
本文作者相关文章
中国知网
分享