| Co-Investigator(Kenkyū-buntansha) |
HORI Yuichi AFFILIATE HOSPITAL OF KOBE UNIVERSITY SCHOOL OF MEDICINE,FIRST DEPARTMENT OF SUR, 医学部・附属病院, 医員
UEDA Takashi AFFILIATE HOSPITAL OF KOBE UNIVERSITY SCHOOL OF MEDICINE,FIRST DEPARTMENT OF SUR, 医学部・附属病院, 医員
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
The mechanism for organ failure in acute pancreatitis has not been clarified. Recently, apoptosis have been reported in organ failures with various conditions. Thus we hypothesized that apoptosis is involved in organ failures with severe acute pancreatitis. Necrotizing hemorrhagic pncreatitis was induced on rats by retrograde injection of sodium deoxycholate into pancreatic duct. Pancreatitis-associated ascitic fluid, which was collected 6 hours after development of pancreatitis, was injected intraperitoneally into untreated rats. Apoptosis was surveyed on the liver, kidney, and thymus from the rats histochemically by in situ nick-end labeling method and biochemically by DNA electrophoresis. In vitro, rat primary culture hepatocytes, isolated rat renal tubules, and normal rat kidney cell line (MDCK cells) were used, and apoptosis-inducing ability of the ascitic fluid was analyzed by nuclear staining and cell cycle analysis in addition to DNA electrophoresis.
As results, the hepatocytes,
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the renal tubules, and the thymocytes were labeled with in situ nick-end labeling in the rats with necrotizing hemorrhagic pancreatitis. Evident DNA fragmentations were detected in the liver, kidney, and thymus in the rats with pancreatitis. In addition, the hepatocytes and the renal tubules were labeled with in situ nick-end labeling in the rats with intraperitoneal injection of the ascitic fluid. In vitro analyzes, the ascitic fluid reduced cellular viabilities of the hepatocytes and MDCK cells in dose- and time-dependent manners. The ascitic fluid increased the ratios of apoptotic cells of the hepatocytes and MDCK cells in cell cycle analysis. Morphological analysis using nuclear staining fluolescent dye and DNA electrophoresis also indicated that the ascites induced apoptotoc cell death on the hepatocytes, isolated rat renal tubules, and MDCK cells.
In conclusion, apoptotic cell death occurs on liver, kidney, and thymus with severe acute pancreatitis within several hours, and is possibly involved in the mechanism of organ failure through underfined substance (s) in the ascitic fluid associated with severe acute pancreatitis. Less
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