A study on a role of endogenous neuropeptides in the brain in the regulation of hepatobiliary and pancreatic functions

研究了大鼠脑内内源性神经肽在肝功能调节中的作用。将大鼠用乌拉坦麻醉并定位在立体定位装置上。将激光多普勒血流仪探头置于肝脏表面。稳定60分钟后，测量基础肝血流量30分钟，并将红藻氨酸微量注射到延髓中缝苍白肌中。在肽注射后观察肝血流120分钟。在枕大池内预先注射抗TRH多克隆抗体可逆转红藻氨酸对血流动力学的影响。大鼠皮下注射CCl_4（2ml/kg），并进行部分身体束缚应激6h。CCl_4给药前及给药后6h脑池内注射CRF拮抗剂astressin。束缚应激使CCl_4引起的血清ALT从293 +_-11 IU/l升高到398 +_-35 IU/l。脑池内astressin剂量依赖性地抑制束缚应激引起的血清ALT升高。脑池内注射astressin可减轻束缚应激加重的CCl_4引起的肝组织病理学改变。交感神经切断或6-OHDA预处理可消除束缚应激对CCl_4所致肝损伤的加重作用，而肝分支迷走神经切断或阿托品预处理则不能消除束缚应激对CCl_4所致肝损伤的加重作用。

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.