Expression of pancreatitis-associated protein (PAP) in rat spontaneous chronic pancreatitis: effect of herbal medicine Saiko-keishi-to (TJ-10).

Pancreatitis-associated protein (PAP) is almost absent in the normal pancreas but is overexpressed in acute pancreatitis. However, its expression in chronic pancreatitis (CP) is unknown. An herbal medicine Saiko-keishi-to (TJ-10) has long been used clinically for CP, but there is no experimental evidence of the effect of TJ-10 on CP. The aim of this study was to analyze the expression of PAP and the effect of TJ-10 in a spontaneous chronic pancreatitis model. Four-week-old male WBN/Kob rats were fed with a special pellet diet (MB-3), and TJ-10 (80 mg/100 g body weight/day) was orally administered for 16 weeks. The rats were killed at every 4 weeks, and pancreata were histopathologically examined. PAP messenger RNA (mRNA) in the pancreas was detected with a reverse transcription/polymerase chain reaction (RT-PCR) method. The cellular localization of PAP mRNA and protein was analyzed with in situ hybridization (ISH) and immunohistochemistry (IHC). PAP mRNA was expressed from 8 weeks, when the pancreas was still pathologically normal, and reached its peak at 12 weeks, when the pancreatitis first appeared. Then the expression of PAP mRNA was decreased gradually. TJ-10 suppressed the expression of PAP mRNA completely at 8 and 12 weeks. PAP mRNA was slightly expressed at 16 and 20 weeks. ISH and IHC confirmed the PAP mRNA and protein expression in the cytoplasm of acinar cells. These results suggest that PAP mRNA appears before CP, and its peak coincides with the onset of CP. TJ-10 suppressed the PAP expression and delayed the development of CP in the WBN/Kob rat.