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Protection of the liver against CCl_4-induced injury by intramuscular electrotransfer of a kallistatin-encoding plasmid
  • ISSN号:1007-9327
  • 期刊名称:《世界胃肠病学杂志:英文版》
  • 时间:0
  • 分类:Q785[生物学—分子生物学] S858.28[农业科学—临床兽医学;农业科学—兽医学;农业科学—畜牧兽医]
  • 作者机构:[1]Institute of Molecular Medicine, Huaqiao University, Quanzhou362021, Fujian Province, China, [2]Centre for Reproduction and Genomics,AgResearch, Invermay, Mosgiel 9053, New Zealand
  • 相关基金:Supported by The State High Technology Research and Development Program of China (863 Program),No.2008AA02Z135; the Important National Science and Technology Specific Projects,No.2009ZX09103-643; the Natural Science Foundation of China,No.30973591
中文摘要:

瞄准:为了在碳四氯化物(CCl4 ) 上调查 kallistatin (Kal ) 的转基因的表示的效果,导致了肝损害由肌内(im )编码 Kal plasmid 的 electrotransfer 与 poly-L-glutamate (PLG ) 提出了。方法:编码 Kal 基因的 pKal plasmid 与 PLG 和 electrotransferred 被提出进老鼠在 CCl4 的管理前的骨胳的肌肉。Kal 的表示水平被测量。丙氨酸 aminotransferase (中高音) 的浆液 biomarker 层次, aspartate aminotransferase (著名计算机生产厂商) , malonyldialdehyde (MDA ) ,和肿瘤坏死因素(TNF )-alpha 被监视。导致 CCl4 的肝损害的程度组织病理学说地被分析。结果:在与 PLG 提出的 plasmid 的 im 注射由 electroporation 列在后面以后, Kal 的 transgene 足够地被表示。在 Kal 转移基因的鼠标,对导致 CCl4 的肝损害的保护被显著地减少的浆液中高音,著名计算机生产厂商, MDA 和 TNF-alpha 层次在控制鼠标与那些相比反映(P 【 0.01 ~ 0.05 以一种剂量依赖者方式) 。组织学的观察也表明那 hepatocyte 坏死,出血, vacuolar 变化和 hydropic 退化在在 CCl4 管理以后的老鼠是明显的。相反,损坏显著地在 Kal 转移基因的老鼠被稀释。标记转变生长 factor-beta1 也是的肝的 fibrogenesis 的表示在 pKal 减少了转移老鼠。结论:显著地与 PLG 被提出的 plasmid pKal 的肌内的 electrotransfer 减轻了导致 CCl4 的氧化压力和煽动性的反应,并且在一个老鼠模型减少了肝损坏。

英文摘要:

AIM:To investigate the effect of transgenic expression of kallistatin(Kal) on carbon tetrachloride(CCl 4)induced liver injury by intramuscular(im) electrotransfer of a Kal-encoding plasmid formulated with poly-Lglutamate(PLG).METHODS:The pKal plasmid encoding Kal gene was formulated with PLG and electrotransferred into mice skeletal muscle before the administration of CCl 4.The expression level of Kal was measured.The serum biomarker levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),malonyldialdehyde(MDA),and tumor necrosis factor(TNF)-α were monitored.The extent of CCl 4-induced liver injury was analyzed histopathologically.RESULTS:The transgene of Kal was sufficiently expressed after an im injection of plasmid formulated with PLG followed by electroporation.In the Kal gene-transferred mice,protection against CCl 4-induced liver injury was reflected by significantly decreased serum ALT,AST,MDA and TNF-α levels compared to those in control mice(P 0.01 to 0.05 in a dose-dependent manner).Histological observations also revealed that hepatocyte necrosis,hemorrhage,vacuolar change and hydropic degeneration were apparent in mice after CCl 4 administration.In contrast,the damage was markedly attenuated in the Kal gene-transferred mice.The expression of hepatic fibrogenesis marker transforming growth factor-β1 was also reduced in the pKal transferred mice.CONCLUSION:Intramuscular electrotransfer of plasmid pKal which was formulated with PLG significantly alleviated the CCl 4-induced oxidative stress and inflammatory response,and reduced the liver damage in a mouse model.

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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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