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Cystamine ameliorates liver fibrosis induced by carbon tetrachloride via inhibition of tissue transglutaminase
  • ISSN号:1007-9327
  • 期刊名称:《世界胃肠病学杂志:英文版》
  • 时间:0
  • 分类:R512.6[医药卫生—临床医学;医药卫生—内科学]
  • 作者机构:[1]Department of General Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, China
  • 相关基金:Supported by National Natural Science Foundation of China, No. 30571825
中文摘要:

瞄准:调查织物 transglutaminase (tTG ) 的反纤维变性效果肝上的特殊抑制剂包囊胺纤维变性。方法:68 只男 Sprague Dawley 老鼠被划分成三个组:正常控制,肝纤维变性控制和对待 cystamine 的组。肝纤维变性被四氯化碳(CCl4 ) 的腹膜内注射导致,并且 Cystamine 被在 CCl4 的第一个政府前开始 2 d 的腹膜内注射管理。在每个组的动物进一步被划分成 2 亚群根据两次 4 wk 和 8 wk 术后疗法指。肝的功能,病理学的评估(半量的得分系统, SSS ) 并且肝羟脯氨酸(忧郁) 内容被检验。实时 PCR 被用来检测 tTG 的表示,平滑肌高山哈肌动朊(alpha-SMA ) , metalloproteinase 的织物禁止者 1 (TIMP-1 ) 并且 collagen-1 mRNA。tTG 和 alpha-SMA 蛋白质的表情被西方的弄污检测。结果:八星期术后疗法,肝的 SSS 分数是显著地,在包囊胺的更少在纤维变性控制组比那组织(P 【 0.01 ) 。丙氨酸 aminotransferase (中高音) 和在 4 wk 和 8 个 wk 时间点的全部的胆汁酸(TBA ) 的层次在纤维变性控制与那些相比在包囊胺组被减少(P 【 0.01 ) 。在 4 wk 和 8 个 wk 时间点的肝羟脯氨酸内容与纤维变性控制相比在包囊胺组显示出实质的减小(P 【 0.01 ) 。tTG, alpha-SMA, collagen-1, TIMP-1 mRNA 和 tTG 的表示,以及 alpha-SMA 蛋白质低与纤维变性控制相比在包囊胺组调整了。结论:Cystamine 能改善 CCl4 导致了肝纤维变性并且保护肝的功能。可能的机制与肝的星形的房间激活的抑制引起并且减少的细胞外的矩阵(ECM ) 的减少的合成有关 TIMP-1 的表示。

英文摘要:

AIM: To investigate the anti-fibrosis effect of the tissue transglutarninase (tTG) specific inhibitor cystarnine on liver fibrosis. METHODS: Sixty-eight male Sprague Dawley rats were divided into three groups: normal control, liver fibrosis control and cystamine-treated group. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl4), and Cystarnine was administrated by intraperitoneal injection starting 2 d before the first administration of CCl4. Animals in each group were further divided into 2 subgroups according to two time points of 4 wk and 8 wk after treatment. Hepatic function, pathological evaluation (semi-quantitative scoring system, SSS) and liver hydroxyproline (Hyp) content were examined. Real-time PCR was used to detect the expression of tTG, smooth muscle alpha actin (α-SMA), tissue inhibitor of metalloproteinase 1 (TIMP-1) and collagen-1 mRNA. The expressions of tTG and α-SMA protein were detected by Western Blotting. RESULTS: Eight weeks after treatment, the SSS score of liver was significantly less in the cystamine group than that in the fibrosis control group (P 〈 0.01). The levels of alanine arninotransferase (ALT) and total bile acid (TBA) at the 4 wk and 8 wk time points were decreased in the cystamine group compared with those in fibrosis controls (P 〈 0.01). Liver hydroxyproline content at the 4 wk and 8 wk time points showed a substantial reduction in the cystamine group compared to fibrosis controls (P 〈 0.01). The expression of tTG, α-SMA, collagen-1, TIMP-1 mRNA and tTG, as well as α-SMA protein was downregulated in the cystamine group compared to fibrosis controls. CONCLUSION: Cystamine can ameliorate CCl4 induced liver fibrosis and protect hepatic function. The possible mechanism is related to the reduced synthesis of the extracellular matrix (ECM) caused by the inhibition of hepatic stellate cell activation and decreased expression of TIMP-1.

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  • 《世界胃肠病学杂志:英文版》
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  • 国际标准刊号:ISSN:1007-9327
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