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.