首页|Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice

Matrix metalloproteinase-9 contributes to parenchymal hemorrhage and necrosis in the remnant liver after extended hepatectomy in mice

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AIM:To investigate the effect of matrix metalloproteinase-9 (MMP-9) on the remnant liver after massive hepatectomy in the mouse.METHODS:Age-matched,C57BL/6 wild-type (WT),MMP-9(-/-),and tissue inhibitors of metalloproteinases (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,immunohistochemical 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 necrotic lesions in MMP-9(-/-) remnant livers compared with WT and TIMP-1(-/-) livers (P ＜ 0.01),with no difference between WT and TIMP-1(-/-) mice.Serum alanine aminotransaminase levels were significantly lower in MMP-9(-/-) mice compared with those in TIMP-1(-/-)mice (WT:476 ± 83 IU/L,MMP-9(-/-):392 ± 30 IU/L,TIMP-1(-/-):673 ± 73 IU/L,P ＜ 0.01).Western blotting 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 suggestthat 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 might be a potential therapy to ameliorate liver injury after massive hepatectomy.

Matrix metalloproteinaseLiver remnantHepatectomyLiver failureNecrosis

Norifumi Ohashi、Tomohide Hori、Florence Chen、Sura Jermanus、Christopher B Eckman、Akimasa Nakao、Shinji Uemoto、Justin H Nguyen

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Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya,Aichi 466-8550, Japan

Divisions of Hepato-Pancreato-Biliary, Transplant and Pediatric Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan

Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224,United States

Division of Transplant Surgery, Department of Transplantation, Mayo Clinic, Jacksonville, FL 32224,United States

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Nguyen JH from the Deason Foundation,Sandra and Eugene Davenport,Mayo Clinic CD CRT-Ⅱ,and from the National Institutes of HealthHori T from the Uehara Memorial FoundationHori T from the Uehara Memorial FoundationHori T from the Uehara Memorial Foundation

200940051Tokyo 171-0033Japan

2012

10.3748/wjg.v18.i19.2320

世界胃肠病学杂志(英文版)
太原消化病研治中心

世界胃肠病学杂志(英文版)

SCI
影响因子：1.001
ISSN：1007-9327
年,卷(期)：2012.18(19)
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