Schmahl W G, Plendl J, Reinöhl-Kompa S
Res Commun Chem Pathol Pharmacol. 1987 Jan;55(1):89-99.
The role of endogenous opioid systems in preweaning development after intrauterine exposure to X-irradiation or ethylnitrosourea (ENU) was explored in rats using naltrexone, a potent antagonist of beta-endorphin. After daily s.c. injections of 50 mg/kg naltrexone only the prenatally untreated controls had body weights increased by 11% from control level on day 28 (weaning). In the X-irradiated as well as the ENU-treated pups no significant effects of naltrexone on body weight gain were observed. However, brain weight increased in all animals under the influence of naltrexone, irrespective of prenatal treatment or the severity of brain lesions: 9.5% above control values in untreated offspring and 14% after X-irradiation (1 Gy) on gestation day 14. The brain weight of ENU-treated rats (50 mg/kg on gest. day 14) was 13% higher after postnatal naltrexone application than that of their postnatally untreated counterparts. ENU (80 mg/kg) effects on the brain when given on gestation day 18 were ameliorated to 9.2% by naltrexone in the weaning period. Naltrexone significantly increased the thymus weight in controls. Prenatally treated animals also showed an increased thymus weight at weaning, presumably due to compensatory growth. In these cases naltrexone revealed a suppressive effect on the thymus, whereas spleen weight was apparently not influenced by naltrexone treatment. These results provide compelling evidence that endogenous opioid systems play a crucial role not only in normal development, but also in reparative growth events of the brain after prenatal injuries. The thymus, predominantly containing T-lymphocytes, seems to represent another sensitive system which is regulated under the influence of opioids.
利用β-内啡肽的强效拮抗剂纳曲酮，在大鼠中探索了内源性阿片系统在子宫内暴露于X射线或乙基亚硝基脲（ENU）后断奶前发育中的作用。每天皮下注射50mg/kg纳曲酮后，只有未接受产前处理的对照组在第28天（断奶）时体重比对照水平增加了11%。在接受X射线照射以及ENU处理的幼崽中，未观察到纳曲酮对体重增加有显著影响。然而，在纳曲酮的影响下，所有动物的脑重均增加，无论产前处理情况或脑损伤的严重程度如何：未处理后代的脑重比对照值高9.5%，妊娠第14天接受1Gy X射线照射后的脑重比对照值高14%。产后应用纳曲酮后，ENU处理大鼠（妊娠第14天给予50mg/kg）的脑重比未接受产后处理的对应大鼠高13%。在断奶期，纳曲酮使妊娠第18天给予80mg/kg ENU对脑的影响减轻至9.2%。纳曲酮显著增加了对照组的胸腺重量。产前处理的动物在断奶时胸腺重量也增加，可能是由于代偿性生长。在这些情况下，纳曲酮对胸腺有抑制作用，而脾脏重量显然不受纳曲酮处理的影响。这些结果提供了令人信服的证据，表明内源性阿片系统不仅在正常发育中起关键作用，而且在产前损伤后脑的修复性生长事件中也起关键作用。主要含有T淋巴细胞的胸腺似乎代表了另一个受阿片类物质影响而调节的敏感系统。
