Research on pancreatic stellate cell activation and experimental pancreatic fibrosis

Objective To study the significance and role of pancreatic stellate cells (PSCs) in pancreatic fibrosis in the early time of acute pancreatitis by determining the expression of transforming growth factor-β_1(TGF-β_1) messenger RNA and deposition of collagen- Ⅰ,α-smooth muscle actin(α-SMA)in acute pancreatitis. Methods Acute pancreatitis was induced in rats by hyperstimulation with cerulein(50 μg·kg -1 ·day -1 ) and concurrent pancreatic duct obstruction for 72 and 120 hours. Sham animals were injected pure water and underwent laparotomy and manipulation of the pancreas without duct obstruction. Entire pancreas was harvested at the timepoint of 0,72 and 120 hours. Immunohistochemistry was used for examining collagen-Ⅰ and α-smooth muscle actin antibodies. Messenger RNA of transforming growth factor-β_1 (TGF-β_1) was detected by reversal transcription-polymerase chain reaction(RT-PCR).Results There were occasional α-SMA-positive cells (pancreatic stellate cells) in the sham animals and there was none for collagen-Ⅰ staining. Within 72 hours in model animals, α-SMA-positive cells appeared around pancreatic acini. The appearance of these cells were followed by collagen-Ⅰpositive staining. At 120 hours, the above staining progressed gradually. TGF-β_1 mRNA was not found in sham animals.At 72 hours and 120 hours, it showed obvious expression,and expression at 72 hours is a little more than that at 120 hours. Conclusions TGF-β_1 stimulated by acute pancreatic inflammation results in activation of pancreatic stellate cells (α-SMA-positive cells ) and stellate cells gradually secrete collagen and matrix which leads to pancreatic fibrosis finally.