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成纤维细胞生长因子21对小鼠肝纤维化的作用及其机制
Effect of fibroblast growth factor 21 on hepatic fibrosis in mice and its mechanism
文章发布日期:2018年05月07日  来源:  作者:王大秀,韩继武  点击次数:290次  下载次数:29次

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【摘要】:目的探索成纤维细胞生长因子(FGF)21对小鼠肝纤维化的作用及机制。方法将40只雄性ICR小鼠随机分为对照组(n=10)、模型组(CCl4处理)(n=15)、治疗组(CCl4+1.0 mg/kg FGF21处理)(n=15)。连续处理36 d后取血清及肝组织。检测ALT、AST、ALP、TBil、IL-6、IL-1β、TNFα水平;Masson染色观察病理改变;4-羟脯氨酸(4-Hyp)试剂盒检测肝内4-Hyp水平;real-time PCR检测肝胶原蛋白Ⅰ(CollagenⅠ)、α-平滑肌肌动蛋白(α-SMA)、TGFβ、IL-6、IL-1β、TNFα mRNA水平。计量资料多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验。结果Masson染色结果显示,模型组肝纤维化程度较对照组明显加重,治疗组肝纤维化程度较模型组明显减轻;生化检测结果显示,模型组小鼠血清ALT、AST、ALP、TBil水平明显高于对照组,差异均有统计学意义(P值均<0.05);治疗组小鼠血清ALT、AST、ALP、TBil水平较模型组明显下降,差异均有统计学意义(P值均<0.05)。血清ELISA检测结果显示,模型组小鼠血清IL-6、IL-1β、TNFα水平明显高于对照组,差异均有统计学意义(P值均<0.05);治疗组小鼠血清IL-6、IL-1β、TNFα水平较模型组明显下降,差异均有统计学意义(P值均<0.05)。4-Hyp及real-time PCR检测结果显示,模型组4-Hyp以及CollagenⅠ、α-SMA mRNA水平较对照组明显升高,差异均有统计学意义(P值分别为0.004、<0001、<0001);治疗组4-Hyp以及CollagenⅠ、α-SMA mRNA水平明显低于模型组,差异均有统计学意义(P值分别为0.005、<0001、<0001);模型组小鼠肝内TGFβ、IL-6、IL-1β、TNFα mRNA水平较对照组明显升高,差异均有统计学意义(P值均<0001);治疗组小鼠肝内TGFβ、IL-6、IL-1β、TNFα mRNA水平明显低于模型组,差异均有统计学意义(P值均<0001)。结论FGF21改善小鼠肝纤维化的作用机制与抑制肝内TGFβ和IL-6、IL-1β、TNFα等炎症因子表达有关。
【Abstract】:ObjectiveTo investigate the effect of fibroblast growth factor 21 (FGF21) on hepatic fibrosis in mice and the mechanism of its action. MethodsMale ICR mice were randomly divided three groups: control group, model group (treated with CCl4), and treatment group (treated with CCl4 + 1.0 mg/kg FGF21). All mice were sacrificed to collect serum and liver tissues after 36 consecutive days of treatment. Serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBil), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were measured. Liver pathological changes were analyzed by Masson staining. The hepatic 4-hydroxyproline (4-Hyp) level was measured using a hydroxyproline detection kit. The mRNA levels of hepatic collagen I, α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), IL-6, IL-1β, and TNF-α were determined by quantitative real-time PCR. Comparison between multiple groups was made by one-way analysis of variance, and comparison between any two groups weas made using the LSD-t test. ResultsThe Masson staining showed that the model group had a significantly higher degree of hepatic fibrosis than the control group, and the treatment group had a significantly lower degree of hepatic fibrosis than the model group. The model group had significantly higher serum levels of ALT, AST, ALP, and TBil (all P<0.05), and the treatment group showed significant reductions in the above parameters compared with the model group (all P<0.05). Enzyme-linked immunosorbent assay indicated that the model group had significantly higher serum levels of IL-1β, IL-6, and TNF-α than the control group (all P<0.05), and the treatment group showed significant reductions in the above parameters compared with the model group (all P<0.05). The hepatic 4-Hyp level and mRNA levels of collagen I and α-SMA were significantly higher in the model group than in the control group (P=0.04, <0001, and <0001), and they were significantly lower in the treatment group than in the model group (P=0.005,<0001, and <0001). The hepatic mRNA levels of TGF-β, IL-6, IL-1β, and TNF-α were significantly higher in the model group than in the control group(all P<0001), and they were significantly lower in the treatment group than in the control group(all P<0001). ConclusionFGF21 attenuates hepatic fibrogenesis in mice, possibly by inhibiting the expression of TGF-β, IL-6, IL-1β, and TNF-α in the liver.
【关键字】:肝硬化; 成纤维细胞生长因子21; 细胞因子类; 小鼠, 近交ICR
【Key words】:liver cirrhosis; fibroblast growth factor 21; cytokines; mice, inbred ICR
【引证本文】:
WANG DX, HAN JW. Effect of fibroblast growth factor 21 on hepatic fibrosis in mice and its mechanism[J]. J Clin Hepatol, 2018, 34(6): 1215-1219. (in Chinese) 王大秀, 韩继武. 成纤维细胞生长因子21对小鼠肝纤维化的作用及其机制[J]. 临床肝胆病杂志, 2018, 34(6): 1215-1219.

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