Tuomisto J, Andrzejewski W, Unkila M, Pohjanvirta R, Linden J, Vartiainen T, Tuomisto L
Department of Toxicology, National Public Health Institute, Kuopio, Finland.
Eur J Pharmacol. 1995 Mar 16;292(3-4):277-85. doi: 10.1016/0926-6917(95)90033-0.
Portocaval anastomosis and vagotomy operations were performed in Long-Evans (L-E) and Han/Wistar (H/W) rats to elucidate the mechanism of anorexia induced by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). TCDD-sensitive L-E rats were given a sublethal (5 micrograms/kg) or a lethal dose (20 micrograms/kg) by gavage 5-8 weeks after portocaval anastomosis. TCDD-resistant H/W rats were given a nonlethal dose (500 or 7200 micrograms/kg). The shunt operation did not reduce lethality from TCDD. The effect on wasting of the marginally toxic dose of 5 micrograms/kg in L-E rats was potentiated by the portocaval operation, and the lethal dose was effective in both shunted and sham-operated L-E rats. TCDD failed to decrease food intake and body weight in shunted rats of H/W strain at either dose level though it did so in sham-operated controls. The lack of effect may be due to the already reduced weight of shunted rats at the time of TCDD dosing. TCDD anorexia was not explained by changes in histamine or serotonin (5-HT) turnover in the brain. Vagotomy did not influence lethality after TCDD, although reduction in food intake was somewhat blunted in H/W rats. The results seem to indicate that the anorectic effect of TCDD is modified when portal blood bypasses the liver. The mechanisms remain to be elucidated in detail, but the results do not favor the role of liver as the only or the major initiator of TCDD anorexia. Little evidence was found to support a crucial role of vagal afferent input.
为阐明2,3,7,8-四氯二苯并对二恶英（TCDD）所致厌食症的机制，对长-伊文斯（L-E）大鼠和汉/威斯塔（H/W）大鼠进行了门腔静脉吻合术和迷走神经切断术。在门腔静脉吻合术后5至8周，给对TCDD敏感的L-E大鼠经口灌胃亚致死剂量（5微克/千克）或致死剂量（20微克/千克）的TCDD。给对TCDD有抗性的H/W大鼠经口灌胃非致死剂量（500或7200微克/千克）。分流手术并未降低TCDD所致的致死率。门腔静脉手术增强了5微克/千克的边缘毒性剂量对L-E大鼠消瘦的影响，致死剂量对分流和假手术的L-E大鼠均有效。尽管TCDD能使假手术对照组的H/W品系大鼠的食物摄入量和体重下降，但在两个剂量水平下，TCDD均未能使分流的H/W品系大鼠的食物摄入量和体重下降。这种无效应可能是由于在给予TCDD时，分流大鼠的体重已经减轻。大脑中组胺或5-羟色胺（5-HT）代谢的变化并不能解释TCDD所致的厌食症。迷走神经切断术并不影响TCDD后的致死率，尽管H/W大鼠的食物摄入量减少有所减弱。结果似乎表明，当门静脉血绕过肝脏时，TCDD的厌食效应会发生改变。其机制仍有待详细阐明，但结果并不支持肝脏是TCDD厌食症的唯一或主要启动因素这一观点。几乎没有证据支持迷走神经传入输入起关键作用。
