兰州大学机构库 >学院待认领
维生素D 缺乏诱发小鼠肝脏慢性炎症与早期纤维化的特征及部分可能机制
Alternative TitleThe character and partial possible mechanism of mice liver inflammation and fibrosis induced by Vitamin D
朱陇东
Thesis Advisor段钟平 ; 袁宏
2015-05-24
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name博士
Keyword炎症 纤维化 凋亡 维生素D 小鼠
Abstract目的:构建维生素D缺乏小鼠肝脏慢性炎症和早期纤维化模型,并初步探讨部分可能机制。研究方法:1. 建立维生素D缺乏诱导肝脏炎症和纤维化小鼠模型。2.维生素D缺乏影响小鼠肝细胞凋亡。研究结果:1.9周时CCL4组和VDD组ALT 、AST显著高于Normal组;CCL4、VDD组炎症评分显著高于Normal组;VDD组、CCL4组肝组织纤维沉积较Normal组增多; VDD组MMP9活性低于Normal组,MMP2高于Normal组;VDD组CD14、TLR-4、IL-1β、IL-6、TNF-a表达升高,IL-10、IL-13、HO-1表达降低,MCP-1表达升高,α-SMA、ColⅠ、ColⅢ、TGF-β、MMP13、TIMP-1表达升高,MMP9表达下降。2.肝组织TUNEL染色结果:Normal组弱于VDD组和CCL4组;Fas染色在CCL4、VDD组强于Normal组。Fas-L染色在3组小鼠肝组织表达程度接近。Caspase3染色CCL4、VDD组强于Normal组;VDD组较Normal组Bcl-2、Bcl-XL 、TGF-α的mRNA表达下调,Bax、Caspase3、TGF-β1的mRNA表达上调。研究结论:1. 成功构建维生素D缺乏诱发的肝脏炎症和纤维化小鼠模型。2.维生素D缺乏促进小鼠相关炎症分子基因表达,抑制抑炎因子表达,Ⅰ型和Ⅲ型胶原基因表达增加,MMP9活性下降,与炎症共同引起肝脏早期纤维化的发生。3. 维生素D缺乏促进小鼠肝细胞凋亡,其机制与上调Fas、Fas-L、Bax、Caspase3、TGF-β1的mRNA表达,下调抗凋亡因子Bcl-2、Bcl-XL 、TGF-α的mRNA表达有关。
Other AbstractAim:To construct an liver inflammation and fibrosis mice model induced by VDD, research possible mechanism.Methods:1. To construct a mice model with liver inflammation and fibrosis induced by VDD.2. To research the effects of VDD on the apoptosis of hepatocyte in mice.Results:1.After 9 weeks, ALT,AST and inflammation of group CCL4 significantly higher than that of Normal. The fiber area in group VDD and CCL4 were bigger than that of Normal.The activity of MMP9 of group VDD was lower than that of group Normal and MMP2 was higher than that of group Normal; The mRNA expression of CD14,TLR-4, IL-1β, IL-6, TNF-αincreased in group VDD. The mRNA expression of IL-10, IL-13, HO-1 decreased. The mRNA expression of α-SMA,ColⅠ,Col Ⅲ,TGF-β,MMP13,TIMP-1 increased. The mRNA expression of MMP9 decreased.2. The results of TUNEL staining: group Normal were weaker than other groups.The Fas staining in group CCL4 and VDD were stronger than that in group Normal. The mRNA expression of Bcl-2,Bcl-XL,TGF-αwere decreased in group VDD than that of group Normal,and mRNA expression of Bax、Caspase3、TGF-β1 increased.Conclusions:1.Successfully build a liver fibrosis and inflammation mice models induced by VDD.2.VDD can promote the gene expression of inflammatory molecules in mice, inhibit expression of anti-inflammatory cytokine. VDD increase mRNA expression of typeⅠand typeⅢcollagen.MMP9 activity decreased.3.VDD can contribute to apoptosis of hepatocytes by increasing mRNA expression of Fas, Fas-L,Bax, Caspase3, TGF-β1 and decreasing mRNA expression of Bcl-2,BCL-XL, and TGF-α.
URL查看原文
Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/222588
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
朱陇东. 维生素D 缺乏诱发小鼠肝脏慢性炎症与早期纤维化的特征及部分可能机制[D]. 兰州. 兰州大学,2015.
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