ABSTRACT
Objective To investigate the role of pancreatic β cell on pancreatic regeneration following experimental acute pancreatitis.Methods Eighty-seven SD male rats were randomly divided into four groups:control group ( n =15 ),STZ group ( n =24),L-Arg group ( n =24 ),STZ + Arg group ( n =24).60 mg/kg of STZ was administrated by intraperitoneal injection to induce the diabetes model.2.5 g/kg body weight of LArg was administrated by intraperitoneal injection to induce the acute pancreatitis model.The rats were sacrificed 1,3,5,7 d later and the serum levels of amylase and glucose were measured.Relative pancreatic weight (pancreatic weight/body weight) were measured.Pancreatic tissue underwent routine pathologic examination,and the percentage of area of necrosis and tissue transformation was calculated.The expression of Reg4 and insulin was performed by immunofluorescence.Results Serum level of glucose significantly increased after STZ injection.After L-Arg injection,serum level of amylase significantly increased,and there was pancreatic tissue edema,necrosis,infiltration of inflammatory cells,which suggested the successful model induction.The percentage of area of necrosis in STZ + L-Arg group was (71.6 ± 6.0) ％ at the 3rd day,which were significantly higher than (42.3 ± 4.0 ) ％ in L-Arg group; the percentage of area of transformation was (45.6 ± 5.4) ％,which were significantly lower than (78.5 ± 6.4) ％ in L-Arg group.Expression of Reg4 in pancreatic islets of STZ + L-Arg group was significantly lower than those in L-Arg group.Conclusions STZ impairs pancreatic β cells,aggravates pancreatic damage following L-arginine induced pancreatitis and inhibits pancreatic regeneration.
ABSTRACT
PURPOSE: Gastrin is a candidate for the growth regulatory factors of the pancreas and may solve the problem of pancreatic atrophy after partial pancreatectomy. The purpose of this study was to evaluate the effect of endogenous gastrin on the normal growth and regeneration of the pancreas (after partial pancreatectomy) in rat. METHODS: Sixty Sprague-Dawley rats (200-230 g) were divided into 6 groups. Group (G)-I and II received sham operation (splenectomy only), and G-III, IV, V, VI received both 66% partial pancreatectomy (PPx) and splenectomy. Endogenous hypergastrinemia was induced in G-II, IV, VI by stomach gavage of 30 mg/kg.day of Lansoprozole (LSP) for 3 weeks. In G-V and VI, L365,260 (ML lab, UK) was given continuously in a dose of 50 microgram/kg/hour intraperitoneally using osmotic mini pump. The rats were sacrificed 3 weeks later, and serum gastrin, the weight and the amount of DNA, RNA, and protein in the remnant pancreas or corresponding part were checked. RESULTS: Serum gastrin concentration was 3-4 times higher in the groups received LSP. LSP stimulated growth of the pancreas (G-I: 11921 vs. G-II: 14220 mg/100 g body weight, p=0.047), and the effect was even greater in partial pancreatectomy groups (G-III: 14616 vs. G-IV: 17318 mg/100 g body weight, p=0.007). Total DNA, RNA, and protein amount in the remnant pancreas showed the same trends as the pancreas weight. The effect of LSP was totally abolished by L365,260 (G-V: 13517 vs. G-VI: 14313 mg/100 g body weight, p>0.047). CONCLUSION: Endogenous gastrin has a stimulatory effect on normal growth, and a much stronger effect on the regeneration of the rat pancreas after partial pancreatectomy. Further investigations including clinical trial should be needed.