| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1996: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Research Abstract |
1.Study on protection of hepatic damage during cold preservation. In our previous studies, we clarified Kupffer cell activation during cold preservation, inducing an injury of simusoidal endothelial cells(SEc) through tissue toxic mediators. In the present study, we attempted to prove an alternative mechanism of SEC injury, that is apoptosis, because SEC damage appeared at earlier peroid than Kupffer cell activation. Consequently, we made clear the apoptotic change of SEC with high frequency during cold preservation by electron microscopy and Tunel method. Furthermore, we found that vascular endothelial growth factor(VEGF) contributed to the suppresssion of apoptosis. In addition, we studied an ultrastructural alteration of cold-preserved fatty liver based on the evidence that a datty liver is one of main risk factors for primary nonfunctioning graft. We found that SEC damage proceeded prior to cold preservation and then accerelated during the preservation. The morphological changes we
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re increase in bleb formation, expansion of gap and string-like appearance in SEC.With regard to hepatocytes, size of fat droplets was enlarged with the duration of cold preservation, and then occupied cytoplasma. This change caused the oppression of sunusoid and narrowness of sinusoidal caliber. These findings suggested that a causative mechanism of graft failure in the transplantation of fatty liver may be microcirculatory disturbance of hepatic sinusoid. 2.Discovery of Na-Ca exchanger in Ito cells. Ito cells are adhered to outlayr of sinusoid, and is considered to be participated in the regulation of sinusoidal circulation by the own contraction. This contraction is regulated by the cytoplasmic Ca ion concentration. In the present study, we discovered first Na-Ca exchanger in Ito cells and further found that the expression of the mRNA and the protein was closely correlated with the activation of Ito cells and liver fibrosis. 3.Significance of nitric oxide(NO) in portal hemodynamics of liver cirrhosis. More recently, evidence has accumulated indicating that NO is closely related to the hyperdynamic change seen in the liver cirrhosis. However, the role of NO in this pathology is still remained to be resolved. In the present study we demonstrated that NO plays a significant role in portal hypertensive hemodynamics in CCl_4-induced liver cirrhosis, and that NO is a useful indicator for the evaluation of portal hypertension. Furthermore, the increased serum levels of NO were found to be derived at least in part from the increased expression of iNOSmRNA in the liver, spleen and lung. Less
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