New drug delivery system for liver sinusoidal endothelial cells for ischemia-reperfusion injury

Naoki Sano, Takafumi Tamura, Naoyuki Toriyabe, Takeshi Nowatari, Ken Nakayama, Tomohito Tanoi, Soichiro Murata, Yu Sakurai, Mamoru Hyodo, Kiyoshi Fukunaga, Hideyoshi Harashima, Nobuhiro Ohkohchi

研究成果: Article査読

7 被引用数 (Scopus)


AIM: To investigate the cytoprotective effects in hepatic ischemia-reperfusion injury, we developed a new formulation of hyaluronic acid (HA) and sphingosine 1-phophate. METHODS: We divided Sprague-Dawley rats into 4 groups: control, HA, sphingosine 1-phosphate (S1P), and HA-S1P. After the administration of each agent, we subjected the rat livers to total ischemia followed by reperfusion. After reperfusion, we performed the following investigations: alanine aminotransferase (ALT), histological findings, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, and transmission electron microscopy (TEM). We also investigated the expression of proteins associated with apoptosis, hepatoprotection, and S1P accumulation. RESULTS: S1P accumulated in the HA-S1P group livers more than S1P group livers. Serum ALT levels, TUNEL-positive hepatocytes, and expression of cleaved caspase-3 expression, were significantly decreased in the HA-S1P group. TEM revealed that the liver sinusoidal endothelial cell (LSEC) lining was preserved in the HA-S1P group. Moreover, the HA-S1P group showed a greater increase in the HO-1 protein levels compared to the S1P group. CONCLUSION: Our results suggest that HA-S1P exhibits cytoprotective effects in the liver through the inhibition of LSEC apoptosis. HA-S1P is an effective agent for hepatic ischemia/reperfusion injury.

ジャーナルWorld Journal of Gastroenterology
出版ステータスPublished - 2015 12月 7

ASJC Scopus subject areas

  • 消化器病学


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