2002 Fiscal Year Final Research Report Summary
Possible Role of Serotonin in Hepatic Ischemia and Reperfusion Injury in Rat
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants |
|Research Institution||Nagoya City University |
SUZUKI Tatsuya Nagoya City University, Graduate School of Medical Sciences, Research Associate, 大学院・医学研究科, 助手 (00285222)
HASHIMOTO Takashi Nagoya City University, Graduate School of Medical Sciences, Associate Professor, 大学院・医学研究科, 助教授 (10094393)
|Project Period (FY)
2001 – 2002
|Keywords||serotonin / liver injury / ischemia reperfusion|
Srotoninn is known to induce platelet aggregation and to be a strong vasoconstrictor. Vascular stenosis by the formed thrombi and the vasocontraction aggravates ischemia of peripheral tissues and organs.
The aim of this study was to evaluate possible role of serotonin in hepatic ischemic reperfusion injury in rat by the selective S2-serotonergic receptor antagonist (5HTra).
This study was conducted to investigate the infuence of serotonin on the hepatic microcirculation disturbance after hepatic ischemia and reperfusion (HIR) injury and to evaluate the effect of the selective S2-serotonergic receptor antagonist (5HTra) under these conditions.
3. materials and methods
8 week old Female S/D rats were used. Partial liver ischemia was performed by clamping the pedicles of the medial lobe for 30, 60, 90 minutes. In the 5HTra group, 5HTra was administered at a dose of 10mg/kg by intraabdominal injection 15min before ischemia and 15min before reperfusion.
To determine the extent
of hepatocellular damage during reperfusion, the levels of serum aspartate transaminase (U/L), serum alanine transaminase (U/L) and serum lactate dehydrogenase (U/L) were measured. Blood was withdrawn from the heart before ischemia, 30, 60, 90, 120 minutes. Change in the liver enzymes after ischemia reperfuson in the 5HTra group were compared with those in the control group.
In addition, using specific antibody to the serotonin, to study 5-HT expression in the liver subjected to ischemia and reperfusion, immunochemical staining for 5-HT was then performed.
The intraabdominal administration of selective S2-serotonergic receptor antagonist a significant inhibition of the postreperfusion release of the liver enzymes.
Serotonin was detected in sinusoid in the liver subjected to 90 min of ischemia followed by 60min of reperfusion.
Thus ,we conclude that serotonin is strongly involved in the pathogenesis of ischemia reperfusion injury.
These and other results suggested that serotonin might play critical roles in the pathogenesis of hepatic ischemia and reperfusion injury. Less