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

1.观察促甲状腺激素释放激素(TRH)对大鼠中枢神经系统(CNS)肝脏微循环的影响。用氢气清除法测定乌拉坦麻醉大鼠肝脏微循环。脑池内注射TRH类似物可剂量依赖性地增加肝脏血流量，在30min达到高峰。结论：1.中枢TRH对肝血流的刺激作用可被阿托品、消炎痛、L和迷走神经切断所阻断。用清醒大鼠研究了TRH对肝脏增殖的中枢神经系统作用。脑池内注射TRH类似物可剂量依赖性地刺激肝细胞增殖，48h达高峰，72h恢复至基础状态。中枢TRH对肝细胞增殖的刺激作用可被切断肝支迷走神经、阿托品和吲哚美辛所阻断，但不能被L-NAME所阻断。促肾上腺皮质激素释放因子(CRF)和TRH在CCl_4所致大鼠急性肝损伤中的中枢作用脑池注射TRH类似物可剂量依赖性地抑制CC14诱导的小鼠血清ALT水平的升高，这种抑制作用可被阿托品、吲哚美辛和迷走神经切断所阻断，但不能被L NAME或6-OHDA所阻断。本实验观察了TRH对清醒大鼠肝脏cAMP合成的影响。脑池内TRH类似物刺激肝脏cAMP合成，在12h达到高峰。利用特异性抗体和拮抗剂研究TRH和CRF的特异性脑部位，以及评价内源性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.