| Co-Investigator(Kenkyū-buntansha) |
HIRANO Takashi National Institute of Bioscience and Human Technology, the head of an office, 生命工学研究所, 室長
TAKADA Yasutsugu University of Tsukuba, Instisute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (10272197)
KAWAMOTO Toru University of Tsukuba, Instisute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (30282354)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
[Background]TAK-O44,selective inhibitor of endothelin receptor antagonist, loose its efficacy connecting to albumin after administrated into the vein. To keep the effectiveness of TAK-O44,continuous infusion is needed. Using SB20670,non-peptide inhibitor of endothelin, we estimated its protective effect on the ischemia-reperfusion liver injury. The half life of SB is longer than 2 hours, which shows prolonged effects rather than TAK-O44 alone.
[Result]The sinusoidal perfusion rate in the no-ischemia group remained stable and did not alter throughout the experimental time period as the level of 97.5% at 60 min after sham operation and 97.6% at 120 min, as compared to the perfusion rate prior to clamping. As opposed to the no-ischemia group, the perfusion rates in the ischemia group with NaCl administration were significantly reduced to 65.8±5.4 and 70.2±6.5 at 60 min and 120 min after declamping. However, in the ischemia group treated by SB the perfusion rates remained significantly high
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, as 92.0±2.7 % and 93.3±1.6 % of the rate before clamping at 60 min and 120 min after declamping, respectively. There is no significant difference in those ratios between the ischemia group with SB treatment and the no-ischemia group.
The number of sticking leukocytes per acini in the sinusoid of the no-ischemia group was 0.91±0.3 after the laparotomy, 0.84±0.2 at 60 min and 1.07±0.3 at 120 min. There were no significant differences among the number of sticking leykocytes in no-ischemia group. In contrast, within the ischemia group with NaCl administration that number per acini increased significantly from 1.07±0.2 (before clamping) to 4.31±0.8 at 60 min and reached maximum 5.12±1.0 at 120 min after declamping. On the other hand, the number of leukocytes adhering in the ischemia group with SB administration reduced significantly at 60 and 120 min (1.10±0.2,1.54±0.2,respectively) in comparison to that of the ischemia group treated by NaCl ; the reduced number of leukocytes was the same as that noted in the no-ischemia group.
In terms of the postsinusoidal venule, the mean number of adhering leukocytes per square millimeter of the cut surface demonstrated the tendency to increase even in the no-ischemia group as 87.4±28 at 60min and 69.9±20 at 120 min after sham operation, respectively. In the ischemia group, the number of sticking leukocytes increased significantly by NaCl treatment along with the passage of time as 228±51 and 340±62 at 60 and 120 min after I-R, respectively, in comparison to those in the no-ischemic group, On the other hand, in the SB group the mean number of sticking leukocytes 60 min after declamping was 47.3±13 and it was not significantly different from the corresponding value of 87.4±28 in the no-ischemia group ; however, it significantly increased during the next continuous 60 min and reached a mean value of 208±79 in comparison to the corresponding value of the no-ischemia group. That is, the significant difference between the SB and NaCl groups in terms of the number of sticking leukocytes observed at 60min had disappeared 120 min after I-R.
[Conclusion]SB antagonized the I-R microhemodynamics in the sinusoid. On the other hand, in the postsinusoidal venule it did not antagonize the vasoconstriction and leukocyte sticking and resulted in I-R liver injury. Less
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