Sugihara Masahiro, Sadamori Hiroshi, Nishibori Masahiro, Sato Yasuharu, Tazawa Hiroshi, Shinoura Susumu, Umeda Yuzo, Yoshida Ryuichi, Nobuoka Daisuke, Utsumi Masashi, Ohno Kyotaro, Nagasaka Takeshi, Yoshino Tadashi, Takahashi Hideo Kohka, Yagi Takahito, Fujiwara Toshiyoshi
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama, Okayama, 700-8558, Japan.
Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata, Okayama, Okayama, 700-8558, Japan; Department of Surgery, Fukuyama City Hospital, Fukuyama, Japan.
Am J Surg. 2016 Jan;211(1):179-88. doi: 10.1016/j.amjsurg.2015.06.025. Epub 2015 Sep 3.
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.
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.
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.
Anti-HMGB1 mAb ameliorated IRI and improved the mode of liver regeneration after IRI followed by 70% hepatectomy in rats.
本研究旨在确定抗高迁移率族蛋白B1（HMGB1）单克隆抗体（mAb）对缺血/再灌注损伤（IRI）及肝再生模式的影响。
大鼠接受70%肝切除术，通过夹闭肝十二指肠韧带20分钟造成IRI，然后在松开肝十二指肠韧带前立即给予抗HMGB1 mAb。每个时间点使用5只动物。然后我们评估了IRI、再生参数以及残余肝脏中HMGB1的状态。
抗HMGB1 mAb显著改善了残余肝脏的IRI程度，同时HMGB1蛋白表达下调。70%肝切除术后48小时，Ki67阳性肝细胞的比例显著提高。平均肝细胞大小显著减小，细胞周期蛋白依赖性激酶抑制剂1的表达显著减弱。
抗HMGB1 mAb改善了大鼠70%肝切除术后IRI，并改善了IRI后的肝再生模式。
