Spontaneous and cholecystokinin-octapeptide-promoted regeneration of the pancreas followingl-arginine-induced pancreatitis in rat

Summary

Conclusion

Inl-arginine (Arg)-induced pancreatitis, evidence of acute inflammation was observed on d 1–3. Continuous tissue atrophy became visible at the sites of previous pancreatic necrosis, with simultaneous regeneration of the pancreas, mainly around the Langerhans islets. Administration of low doses of cholecystokinin-octapeptide (CCK-8) increased the inflammatory signs of pancreatitis in the early phase, but subsequently diminished the level of atrophy and accelerated the processes of regeneration in this model of pancreatitis.

Background

The aim of this work was to study the regenerative processes following Arg-induced pancreatitis in rats. Besides the spontaneous regeneration, the effects of low doses of CCK-8 on the laboratory and morphologic parameters in this type of experimental pancreatitis were investigated.

Methods

Male Wistar rats were divided into three groups. In group I, the rats received 200 mg/100 g body weight of Arg ip twice, at an interval of 1 h, and 0.5 mL saline was administered sc twice daily. In group II, besides the same amount of Arg, the rats received 1 μg/kg of CCK-8 sc in 0.5-mL saline twice daily (7am and 7pm). In the control animals (group III), an identical amount of glycine was administered ip instead of Arg at the same times. The rats were examined on d 1, 3, 7, 14, and 28 after pancreatitis induction. The pancreatic weight/body weight ratio (pw/bw) was calculated in each case. The serum levels of amylase, and glucose and the pancreatic contents of soluble protein, trypsin, amylase and DNA were determined, and histologic examinations were performed.

Results

In groups I and II, both pw/bw (3.5±0.2 mg/g and 4.1±0.28 mg/g, respectively) and the serum amylase level (8900±560 IU/L and 11100±1390 IU/L, respectively) were significantly elevated on d 1 vs group III (2.1±0.06 mg/g and 5562±373 IU/L, respectively). Pw/bw was significantly decreased in groups I (0.96±0.12 mg/g, 0.8±0.1 mg/g, and 1.8±0.1 mg/g, respectively) and II (1.4±0.15 mg/g, 1.7±0.2 mg/g, and 1.95±0.1 mg/g, respectively) on d 7, 14, and 28 vs group III (2.6±0.3 mg/g, 3.1±0.15 mg/g, and 2.7 ±0.1 mg/g, respectively), whereas in group II it was significantly elevated vs. group I on d 7 and 14. The pancreatic contents of soluble protein, DNA, trypsin and amylase were significantly decreased on d 3–14 in groups I and II vs group III. The pancreatic DNA level was significantly elevated in group II (1.23±0.2 mg/pancreas) vs group I (0.7±0.1 mg/pancreas) on d 7. In group II, the soluble protein (73.1±15.5 mg/pancreas) and amylase (1104±160 IU/pancreas) levels were significantly elevated on d 14 as was that of trypsin (27.2±3.1 IU/pancreas) on d 28, vs group I (26.4±5.3 mg/p, 525±111 IU/pancreas, and 16.3±1.1 IU/pancreas, respectively). On histologic sections, the signs of acute inflammation of the pancreas were more pronounced in group II than in group I on d 1–3. After that time, in spite of the progressive atrophy of the pancreas, the signs of tissue repair were more expressed in group II.