Anti-high mobility group box 1 monoclonal antibody improves ischemia/reperfusion injury and mode of liver regeneration after partial hepatectomy

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• 作者：Masahiro Sugihara ; M.D.^a ; Hiroshi Sadamori ; M.D. ; Ph.D.^a ; ^b ; Masahiro Nishibori ; M.D. ; Ph.D.^c ; Yasuharu Sato ; M.D. ; Ph.D.^d ; Hiroshi Tazawa ; M.D. ; Ph.D.^a ; Susumu Shinoura ; M.D. ; Ph.D.^a ; Yuzo Umeda ; M.D. ; Ph.D.^a ; Ryuichi Yoshida ; M.D. ; Ph.D.^a ; Daisuke Nobuoka ; M.D. ; Ph.D.^a ; Masashi Utsumi ; M.D.^a ; Kyotaro Ohno ; M.D.^d ; Takeshi Nagasaka ; M.D. ; Ph.D.^a ; Tadashi Yoshino ; M.D. ; Ph.D.^d ; Hideo Kohka Takahashi ; M.D. ; Ph.D.^e ; Takahito Yagi ; M.D. ; Ph.D.^a ; Toshiyoshi Fujiwara ; M.D. ; Ph.D.^a ; ^{toshi_f@md.okayama-u.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Ischemia/reperfusion injury ; Hepatectomy ; High mobility group box 1 ; Liver regeneration
• 刊名：The American Journal of Surgery
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：211
• 期：1
• 页码：179-188
• 全文大小：1668 K

文摘

The purpose of this study is to determine the effects of anti–high mobility group box 1 (HMGB1) monoclonal antibody (mAb) on ischemia/reperfusion injury (IRI) and the mode of liver regeneration.

Methods

Rats underwent 70% hepatectomy with IRI caused by clamping the hepatoduodenal ligament for 20 minutes, followed by the administration of anti-HMGB1 mAb immediately before declamping the hepatoduodenal ligament. Five animals were used for each time point. We then evaluated IRI, regeneration parameters and the status of HMGB1 in remnant livers.

Results

The anti-HMGB1 mAb significantly ameliorated the degree of IRI in the remnant livers in association with the downregulation of HMGB1 protein. The ratio of Ki67-positive hepatocytes at 48 hours after 70% hepatectomy was significantly improved. Mean hepatocyte size was significantly reduced and cyclin-dependent kinase inhibitor 1 expression was significantly attenuated.

Conclusions

Anti-HMGB1 mAb ameliorated IRI and improved the mode of liver regeneration after IRI followed by 70% hepatectomy in rats.