Project/Area Number |
12670512
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Gastroenterology
|
Research Institution | Dokkyo University School of Medicine |
Principal Investigator |
YONEDA Masashi Dokkyo University School of Medicine, Assistant Professor, 医学部, 講師 (30261407)
|
Co-Investigator(Kenkyū-buntansha) |
寺野 彰 獨協医科大学, 医学部, 教授 (50155470)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | hepatic pathophysiology / neuropeptide / neurotransmitter / liver injury / stress / automatic nervous system |
Research Abstract |
A role of endogenous neuropeptides in the brain in the regulation of hepatic function was investigated in rats. Rats were anesthetized with urethane and positioned on stereotaxic apparatus. A probe of Laser Doppler flowmeter was placed on the surface of the liver. After 60 min stabilization, basal hepatic blood flow was measured for 30 min, and kainic acid was microinjected into the medullary raphe pallidus. Hepatic blood flow was observed for 120 min post peptide injection. Microinjection of kainic acid into the hemodynamics was reversed by pre-injection of polyclonal anti-TRH antibody in the cisterna magna. Rats were injected with CCl_4 (2ml/kg) subcutaneously and subjected to partial body restraint stress for 6h. CRF antagonist, astressin, was injected intracisternally just before and 6h after CCl_4 administration. Restraint stress exacerbated CCl_4-induced elevation of serum ALT from 293 +__- 11 IU/l to 398 +__- 35 IU/l. Intracisternal astressin dose-dependently inhibited the serum ALT elevation induced by restraint stress. Intracisternal astressin reduced CCl_4-induced liver histological change exacerbated by restraint stress. The exacerbating effect of restraint stress on CCl_4-induced liver damage was abolished by sympathectomy or 6-OHDA pretreatment but not by hepatic branch vagotomy or atropine pretreatment.
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