A study on the effect of central neuropeptides on hepatic function.

1. 研究了促甲状腺素释放激素（TRH）对大鼠肝脏微循环中枢神经系统的影响。用氢气清除率法测定尿素麻醉大鼠肝脏微循环。肝内注射TRH类似物剂量依赖性增强肝血流，30min时达到峰值。阿托品、吲哚美辛、L-NAME和迷走神经切断术可消除中央TRH对肝血流的刺激。研究了TRH对清醒大鼠肝细胞增殖的中枢神经系统影响。通过胸腺嘧啶并入肝DNA来评估肝增殖。肝内TRH类似物对肝增殖的刺激呈剂量依赖性，在肽注射后48 h达到峰值，72 h恢复到基础水平。肝支迷走神经切开术、阿托品和吲哚美辛可消除中央TRH对肝增殖的刺激，但l - name不能。TRH和促肾上腺皮质激素释放因子（CRF）对cc14诱导的清醒大鼠急性肝损伤的中枢神经系统影响。脑内TRH类似物剂量依赖性地抑制CC14注射后24 h血清ALT水平升高，阿托品、吲哚美辛和迷走神经切开术可消除这种抑制作用，而L-NAME和6-OHDA则不能。肝内CRF剂量依赖性增强CC14.4所致肝损害。研究了TRH对清醒大鼠肝脏cAMP合成的中枢神经系统影响。内源性TRH类似物刺激肝脏cAMP合成，并在12小时达到峰值反应。研究TRH和CRF在脑内的特异性位点，并利用特异性抗体和拮抗剂评估内源性TRH和CRF在肝功能中的作用是有意义的。

1. The central nervous system (CNS) effect of thyrotropin releasing hormone (TRH) on hepatic microcirculation was studied in rats. Hepatic microcirculation was measured by hydrogen-gas clearance method in urethane-anesthetized rats. Intracisternal injection of TRH analog dose-dependently enhanced hepatic blood flow with peak response at 30 min. The stimulation of hepatic blood flow by central TRH was abolished by atropine, indomethacin, L-NAME and vagotomy.2. The CNS effect of TRH on hepatic proliferation was studied in awaked rats. Hepatic proliferation was assessed by thymidine incorporation into hepatic DNA.Hepatic proliferation was dose-dependently stimulated by intracisternal TRH analog with peak response at 48 h after the peptide injection and returned to basal at 72 h. Stimulation of hepatic proliferation by central TRH was abolished by hepatic branch vagotomy, atropine and indomethacin but not by L-NAME.3. The CNS effect of TRH and corticotropin releasing factor (CRF) on CC14-induced acute liver damage in awaked rats. Intracisternal TRH analog dose-dependently inhibited the elevation of serum ALT level 24 h after CC14 injection and this inhibitory effect was abolished by atropine, indomethacin and vagotomy, but not by L-NAME or 6-OHDA.Intracisternal CRF dose dependently enhanced hepatic damage induced by CC14.4. The CNS effect of TRH on hepatic cAMP synthesis was studied in awaked rats. Intracisternal TRH analog stimulate hepatic cAMP synthesis with peak response at 12 h.It is of interest to investigate specific brain sites for TRH and CRF and to evaluate a role of endogenous TRH and CRF in hepatic function using specific antibody and antagonist.