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-Lglutam...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.展开更多
Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, how...Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate （DBP; from gestational day （GD） 14.5 to postnatal day （PND） 6） or diethylstilbestrol （DES; from GD14o5 to GD16.5） during a short gestationalllactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.展开更多
基金Supported by The State High Technology Research and Development Program of China (863 Program),No.2008AA02Z135the Important National Science and Technology Specific Projects,No.2009ZX09103-643the Natural Science Foundation of China,No.30973591
文摘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.
文摘Maternal exposure to estrogenic xenobiotics or phthalates has been implicated in the distortion of early male reproductive development, referred to in humans as the testicular dysgenesis syndrome. It is not known, however, whether such early gestational and/or lactational exposure can influence the later adult-type Leydig cell phenotype. In this study, Sprague-Dawley rats were exposed to dibutyl phthalate （DBP; from gestational day （GD） 14.5 to postnatal day （PND） 6） or diethylstilbestrol （DES; from GD14o5 to GD16.5） during a short gestationalllactational window, and male offspring subsequently analysed for various postnatal testicular parameters. All offspring remained in good health throughout the study. Maternal xenobiotic treatment appeared to modify specific Leydig cell gene expression in male offspring, particularly during the dynamic phase of mid-puberty, with serum INSL3 concentrations showing that these compounds led to a faster attainment of peak values, and a modest acceleration of the pubertal trajectory. Part of this effect appeared to be due to a treatment-specific impact on Leydig cell proliferation during puberty for both xenobiotics. Taken together, these results support the notion that maternal exposure to certain xenobiotics can also influence the development of the adult-type Leydig cell population, possibly through an effect on the Leydig stem cell population.
