Abstract
s / Pancreatology 13 (2013) e1–e94 e61 Ono Pharmaceutical Co., Ltd., Research Headquarters, Osaka, Japan Background: Chronic pancreatitis (CP) is an intractable disease with destruction of acinar and duct cells, interstitial fibrosis, and infiltration of inflammatory cells. ONO-1301, a novel sustained release prostacyclin analog, has an anti-fibrotic effect to lung, heart, kidney and liver, partly associated with induction of hepatocyte growth factor (HGF). However, its effect on CP is not clear. Aim: The aim of our study was to examine the effect of ONO-1301 on CP. Methods: CP was induced by dibutyltin dichloride (DBTC) (7mg/kg) in rats. Seven days after DBTC injection (day7), a slow release form of ONO1301(10mg/kg) or vehicle (control) was injected. At day 14 and 28, we evaluated histopathological CP score (edema, fatty change, inflammatory cells infiltration and fibrosis), and the expression of HGF, cytokines and collagen type1 in pancreas by realtime PCR. Results: Histopathological CP score was improved in the ONO-1301 treated group (1301 group) compared to control; especially, inflammatory cells infiltration at day 14 and interstitial fibrosis at day 28. HGF mRNA increased significantly after administration of ONO-1301, whereas IL-1b, IL-6, TNF-a, TGF-b, MCP-1 and collagen mRNA decreased significantly at day 14, and collagen, MCP-1 and TGF-b tended to decrease at day 28. Decreased inflammatory cytokines production and inflammatory cells infiltration could attenuate the following fibrosis in 1301 group. These findings might suggest that ONO-1301 suppressed local inflammation at early stage of CP with induction of HGF. Conclusion: ONO-1301 suppressed pancreatic fibrosis in the DBTCinduced CP model through inhibition of inflammatory cells infiltration in the early stage of CP. Similar to other organs, this effect of ONO-1301 might be associated with induction of HGF.
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