| Objective:To prepare the rats model of chronic pancreatitis(CP) and confirm its success, to observe changes of glycometabolism and expression of IKK-βdensity in liver and fatty tissue, so as to study on the intervention of rosiglitazone, aspirin and chaihushugansan and discuss mechanism of overt pancreatogenic diabetes developed by chronic pancreatitis, as well as to provide foundation for the medical research of pancreatogenic diabetes. Methods:Using healthy Wistar rats which were divided into model group and control group. Oleic acid was injected intrapancreatobilliary duct by using I.V.Catheter and microsyringe in model group. The control rats were opened abdominal cavity and only tumbled pancreas instead. Appearance and pathological changes of pancreas, body weight changes were investigated over a period of 6 weeks after induction of this model.6 weeks later, we divided 40 chronic pancreatitis rats model into model group, rosiglitazone group, aspirin group and chaihushugansan group randomly, with 10 rats each group. Adding control group, were 5 groups in all. Oral rosiglitazone was everyone in rosiglitazone group by a dose of 1mg/kg/day. Oral aspirin was everyone in aspirin group by a dose of 50mg/kg/day. Oral chaihushugansan was everyone in chaihushugansan group by a dose of 2.8g/kg/day. Water was administrated to other 2 groups by a dose of 0.5ml/100g/day. Oral glucose tolerance test and insulin tolerance test were carried out 2 weeks later. Then experimental rats were put to death and taken their pancreas, liver,fatty tissue and blood, so as to observe the pathological changes of pancreas, liver and fatty tissue, fasting blood glucose(FBG) and insulin level changes. Using RT-PCR and western blot to detect the expression of IKK-βmRNA and protein. On the other hand, we investigated the influence of the 3 medicine mentioned above. Results:There is no difference in preoperative body weight between model group and control group.While after operation, weight of model rats increased slowly.Especially after 3-6 weeks, weight gain of model rats displayed markedly slow-moving(p<0.05). Model rats displayed impaired glucose tolerance (IGT), FBG markedly increased (p<0.05) and insulin in serum markedly decreased (p<0.05). Rosiglitazone, chaihushugansan and aspirin may effectively improve those abnormalities (p<0.05). Rosiglitazone displayed a better therapeutic efficacy.Histologically, destruction of pancreatic small ducts and acini appeared, with some clearly necrosis and congestion in vascellum. Inflammatory cells most of which were lymphocytes infiltrated with halo around them. Structure of pancreatic islets was destroyed with decrease ofαandβcells. Some tissue demonstrated fiber proliferation. Obviously decreased number of inflammatory cells and lessening fiber proliferation was observed in Chinese medicine group. Reparation of destructive pancreatic islets was observed in Rosiglitazone group with increasedαandβcells, comparing with model group. Diminished number of inflammatory cells was also observed in aspirin group. Inflammatory cells most of which were lymphocytes infiltrated in various degree in header and lobules of liver. Lessened inflammatory cells in therapy groups, Chinese medicine group was best. A small quantity number of lymphocytes infiltrated was observed in fatty tissue, lessened inflammatory cells in therapy groups in some degree, Chinese medicine group was better.RT-PCR showed that expression of IKK-βmRNA in model rats significantly increased comparing with what in control rats (p<0.05). Rosiglitazone, aspirin and chaihushugansan displayed down-regulation to the expression in some degree. The expression of heptic IKK-PmRNA was decreased more significantly in Chaihushugansan therapy group(p<0.05), while in Rosiglitazone therapy group, the expression of IKK-βmRNA in fatty tissue was decreased more significantly(p<0.05). These results agreed with those showed from Western blot.Conclusion:The model of chronic pancreatitis induced by oleic acid demonstrated extensive acinar degeneration and overt damage of islet, accompanying with chronic inflammatory infiltration and tissue fibration. The CP model was succeeded and demonstrated IGT, abnormality of FBG and insulin level in serum. And improvement happened in various degree and various point of view after treated with Rosiglitazone, aspirin and chaihushugansan. Protein and mRNA of IKK-βon liver and fatty tissue increased in model, which may be an important mechanism from chronic pancreatitis, insulin resistance on leading to pancreatogenic diabetes. And improvement happened in various degree and various point of view after treated with Rosiglitazone, aspirin and chaihushugansan. Treatment of integrated Western and Chinese medicine will show better curative effect and prospect on those who suffered from insulin resistance and pancreatogenic diabetes.
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