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

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

来源：World Journal of Gastroenterology, 2015, 21(45): 12778-12786.

DOI：10.3748/wjg.v21.i45.12778

• Hyaluronic acid
• Sphingosine 1-phosphate
• Liver sinusoidal endothelial cell
• Drug delivery system
• Heme oxygenase-1
• Stabilin-2

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.

• 出版日期2015-12-7