Protection of the liver against CCl_4-induced injury by intramuscular electrotransfer of a kallistatin-encoding plasmid

查看全文 作　　者：Yong [1]Diao;Xiao-Feng [1]Zhao;Jun-Sheng [2]Lin;Qi-Zhao [1]Wang;Rui-An [1]Xu

机构地区：[1]Institute of Molecular Medicine, Huaqiao University, Quanzhou362021, Fujian Province, China;[2]Centre for Reproduction and Genomics,AgResearch, Invermay, Mosgiel 9053, New Zealand

出　　处：《World Journal of Gastroenterology》索引2011年第17卷第1期,共7页

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 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. 关键词：基因编码肌肉注射肝损伤质粒诱导肝脏四氯化碳转基因表达

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Protection of the liver against CCl_4-induced injury by intramuscular electrotransfer of a kallistatin-encoding plasmid

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