Alpha-Melanocyte-Stimulating Hormone Gene Transfer Attenuates Inflammation after Bile Duct Ligation in the Rat

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Taipei Medical University Institutional Repository > 公共衛生學院 > 傷害防治學研究所 > 期刊論文 > Item 987654321/2323

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题名:	Alpha-Melanocyte-Stimulating Hormone Gene Transfer Attenuates Inflammation after Bile Duct Ligation in the Rat
作者:	邱文達;洪國盛 Chien-Che Wang;Jia-Wei Lin;Liang-Ming Lee;Chien-Min Lin;Wen-Ta Chiu;Hsin-Te Pai;(Kuo-Sheng Hung)
贡献者:	傷害防治學研究所
日期:	2008
上传时间:	2009-08-18 17:47:16 (UTC+8)
摘要:	Cholestasis occurs in a wide variety of human liver diseases, and hepatocellular injury is an invariant feature of cholestasis causing liver dysfunction and inflammation, promoting fibrogenesis, and ultimately leading to liver failure. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. The aim of this study was to investigate whether the gene transfer of alpha-MSH could attenuate hepatic inflammation after bile duct ligation in the rat. Studies were performed in bile duct-ligated (BDL) rats. Hydrodynamic-based gene transfection with alpha-MSH plasmid via rapid tail vein injection was performed 30 min after ligation of bile duct. The endpoints were studied as markers of inflammation 7 days after bile duct ligation. alpha-MSH expression in liver via a single administration of naked plasmid was demonstrated. Liver inflammation index, including neutrophil infiltration and serum alanine aminotransferase, were significantly reduced in alpha-MSH gene transfer rats. Markers for liver inflammation, including expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and inducible NO synthase (iNOS) mRNA, as assessed by real-time PCR, were also attenuated by alpha-MSH gene therapy. Expression of iNOS protein in liver diminished after alpha-MSH gene transfer. Consistent with these data, hepatic stellate cells (HSC) and Kupffer cells were markedly inhibited in alpha-MSH gene-treated rats. Our findings show that gene transfer of alpha-MSH could attenuate hepatic inflammation after bile duct ligation in the rat.
關聯:	Dig Dis Sci.(53):556-563.
显示于类别:	[傷害防治學研究所] 期刊論文

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