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Severe Chronic Pancreatitis due to Recurrent Acute Injury: Non-Invasive Chronic Pancreatitis Model of Rat

Surendra Sharma, Satya Vati Rana, Surinder Rana, Deepak Kumar Bhasin, Ritambhra Nada, Samir Malhotra

Aim To establish non-invasive chronic pancreatitis model of Rat. Methods Thirty wistar rats (200±50 gm) were given L-arginine hydrochloride (250 mg/100 gm b.wt./day) intraperitoneally in two repeated doses of 1 hour interval on day 1 and repeated with same single dose on day 4,7,10,13,16 and 19. Six animals were sacrificed on day 3, 6 animals on day 9, 6 animals on day 15 whereas rest 6 animals were sacrificed on day 21. Six control rats received sham injections of normal saline and sacrificed on day 21. Biochemical, histopathological, Immunohistochemistry staining for activated pancreatic stellate cells and mRNA expression for TGF-β1, Collagen 1α 1 and Fibronectin 1 were done. Results Pancreas in control group was soft grey with mean weight 3.0±0.19 gm. While, on day 15 and 21, pancreas were small, firm to fatty and weighed 1.9±0.23 gm and 1.8±0.19 gm respectively. Interlobular and intralobular fibrosis replaced 30% of exocrine pancreas after 5 injections on day 15. Inflammation comprised of biliophages and eosinophils along with lymphoplasmacytic cells. Fat infiltration (5-10%) was seen only in 1 case on day 15. However all animals showed marked fibrosis. With continuation of repeated acute injury till day 19, exocrine pancreas showed extensive fat infiltration (30-50%) in addition to fibro inflammatory changes. Only 5-10% of normal exocrine parenchyma persisted till day 21. TNF-α, IL-10 and lipid peroxidation levels were significantly elevated and GSH levels were significantly low in arginine treated animals. IHC staining showed α-SMA (+) activated pancreatic stellate cells on day 15 and day 21. Expression of TGF-β1, Collagen 1α 1 and Fibronectin 1 were also found to be significantly elevated on day 15 and day 21. Conclusion Normal pancreatic exocrine tissue was replaced by fibrosis and inflammation at day 15 after repeated acute injury which when continued till day 21 showed significant fat infiltration and fibrosis.