|Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
Morphological changes of exocrine pancreas in rat pancreatic duct ligation model were investigated. Pancreatic acinar cells were drived to dead with apoptotic process, whichwas detarmined with TUNEL staining and gel electrophoresis, and ductal cells were to proliferate ; however, no change was found in endocrine pancreas. When Bcl-2 family protein, an apoptosis balancer proto-oncogene was studied, Bax and Bcl-XS of apoptosis inducers were over-expressed in acinar cells and Bcl-2, Bcl-XL and MCL-1 of apoptosis blockers were over-expressed in ductal cells. Similar results were obtained in surgically obtained pancreatic tissues of chronic obstructive pancreatitis, i.e.apoptosis of acinar cells and proliferatiion of ductal cells with over-expression of Bcl-2, Bcl-XL and MCL-1 in ductal cells. The results indicate that Bcl-2 proteins and apoptotic process were deeply involved in the mechanism of chronic pancreatitis.
Changes in rat cerulein-induced pancreatitis and ischemia-reperfusion model
, experimental models for acute edematous pancratitis, were also investigated. In the recovering phase of acute pancreatits, apoptotic cell death in acinar cells werefound with elecron microscope, TUNEL staining and gel elctrophoresis, and over-expression of Bax and Bcl-Xs in acinar cells were simultaneously observed. The degree of inflammation was significantly decreased and apoptosis was dramatically increased, when pancreatitis rats were treated with neutrophil depletion. The results suggest that apotpotic cell death is a self-protective process and infiltrated neutrophils act as deterioration of the inflammation.
Furthermore, apoptosis induction by chemotherapy and radiotherapy in human pancreatic cancer cell lines were studied in vitro. These genotoxin caused time-and dose-dependent induction of apoptosis in cancer cells with significant inducition of Bax protein. The cellular susceptability to these agents were significantly correlated with the status of Bax to Bcl-2 ratio of the cancer cells. Less