AIM： To investigate the effect of matrix metallopro- teinase-9 （MMP-9） on the remnant liver after massivehepatectomy in the mouse.METHODS： Age-matched, C57BL/6 wild-type （WT）, MMP-9（-/-）, and tissue inhibitors...AIM： To investigate the effect of matrix metallopro- teinase-9 （MMP-9） on the remnant liver after massivehepatectomy in the mouse.METHODS： Age-matched, C57BL/6 wild-type （WT）, MMP-9（-/-）, and tissue inhibitors of metalloprotein- ases （TIMP）-1（-/-） mice were used. The mice received 80%-partial hepatectomy （PH）. Samples were obtained at 6 h after 80%-PH, and we used histology, immuno- histochemical staining, western blotting analysis and zymography to investigate the effect of PH on MMP-9. The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor.RESULTS： We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis. There were significantly fewer and smaller hemorrhagic and ne- crotic lesions in MMP-9（-/-） remnant livers compared with WT and TIMP-1（-/-） livers （P 〈 0.01）, with no dif- ference between WT and TIMP-1（-/-） mice. Serum ala- nine aminotransaminase levels were significantly lower in MMP-9（-/-） mice compared with those in TIMP-I（-/-） mice （WT： 476± 83 IU/L, MMP-9（-/-）： 392 ± 30 IU/L, TIMP-I（-/-）： 673 ± 73 IU/L, P 〈 0.01）. Western blot- ting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9（-/-） mice, which was in contrast to WT and TIMP-1（-/-） mice. No change in MMP-2 expression was observed in any of the study groups. Similar to MMP-9（-/-） mice, when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001, hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice （P 〈 0.05）. These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver.CONCLUSION： Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and mightbe a potential therapy to ameliorate liver injury after massive hepatectomy.展开更多
基金Supported by Grants to Nguyen JH from the Deason Foundation,Sandra and Eugene Davenport,Mayo Clinic CD CRT-II, and from the National Institutes of Health,No.R01NS05164601A2a grant to Hori T from the Uehara Memorial Foundation, No.200940051,Tokyo 171-0033,Japan
文摘AIM： To investigate the effect of matrix metallopro- teinase-9 （MMP-9） on the remnant liver after massivehepatectomy in the mouse.METHODS： Age-matched, C57BL/6 wild-type （WT）, MMP-9（-/-）, and tissue inhibitors of metalloprotein- ases （TIMP）-1（-/-） mice were used. The mice received 80%-partial hepatectomy （PH）. Samples were obtained at 6 h after 80%-PH, and we used histology, immuno- histochemical staining, western blotting analysis and zymography to investigate the effect of PH on MMP-9. The role of MMP-9 after PH was investigated using a monoclonal antibody and MMP inhibitor.RESULTS： We examined the remnant liver 6 h after 80%-PH and found that MMP-9 deficiency attenuated the formation of hemorrhage and necrosis. There were significantly fewer and smaller hemorrhagic and ne- crotic lesions in MMP-9（-/-） remnant livers compared with WT and TIMP-1（-/-） livers （P 〈 0.01）, with no dif- ference between WT and TIMP-1（-/-） mice. Serum ala- nine aminotransaminase levels were significantly lower in MMP-9（-/-） mice compared with those in TIMP-I（-/-） mice （WT： 476± 83 IU/L, MMP-9（-/-）： 392 ± 30 IU/L, TIMP-I（-/-）： 673 ± 73 IU/L, P 〈 0.01）. Western blot- ting and gelatin zymography demonstrated a lack of MMP-9 expression and activity in MMP-9（-/-） mice, which was in contrast to WT and TIMP-1（-/-） mice. No change in MMP-2 expression was observed in any of the study groups. Similar to MMP-9（-/-） mice, when WT mice were treated with MMP-9 monoclonal antibody or the synthetic inhibitor GM6001, hemorrhagic and necrotic lesions were significantly smaller and fewer than in control mice （P 〈 0.05）. These results suggest that MMP-9 plays an important role in the development of parenchymal hemorrhage and necrosis in the small remnant liver.CONCLUSION： Successful MMP-9 inhibition attenuates the formation of hemorrhage and necrosis and mightbe a potential therapy to ameliorate liver injury after massive hepatectomy.
