Bütikofer E E, Lichtensteiger W, Schlumpf M
Institute of Pharmacology, University of Zurich, Switzerland.
Neurotoxicol Teratol. 1993 Nov-Dec;15(6):377-82. doi: 10.1016/0892-0362(93)90054-r.
Prenatal exposure to low doses of benzodiazepines has been found to affect immune functions (25,26). Because the immune system is controlled by the autonomic nervous system, we investigated the sympathetic activity in the spleen for a possible contribution to impaired immune function. Twenty-eight-day-old offspring of prenatally diazepam- or vehicle-treated Long-Evans rats (diazepam 1.25 mg/kg/day SC, gestational day 14-20) were injected IP with sheep red blood cells (SRBC) to evoke an immune reaction. Baseline splenic noradrenaline (NA) turnover was higher in females than in males. Prenatal diazepam treatment resulted in reduced NA turnover in the spleen of SRBC-stimulated female, but not male, offspring. beta-Adrenergic binding sites in spleen membrane fractions, studied with 3H-dihydroalprenolol, showed no differences, indicating that changes in NA turnover were not compensated by changes in receptor expression. Sex-specific developmental effects of diazepam have been described earlier, e.g., in selective effects on perinatal corticosterone levels in female offspring (26).
已发现产前低剂量接触苯二氮䓬会影响免疫功能（25,26）。由于免疫系统受自主神经系统控制，我们研究了脾脏中的交感神经活动，以探讨其对免疫功能受损可能产生的影响。将产前接受地西泮或赋形剂处理的长 Evans 大鼠（地西泮 1.25 毫克/千克/天，皮下注射，妊娠第 14 - 20 天）的 28 日龄后代腹腔注射绵羊红细胞（SRBC）以引发免疫反应。雌性脾脏去甲肾上腺素（NA）的基础周转率高于雄性。产前地西泮处理导致 SRBC 刺激的雌性后代而非雄性后代脾脏中的 NA 周转率降低。用 3H - 二氢阿普洛尔研究脾脏膜组分中的β - 肾上腺素能结合位点，未发现差异，表明 NA 周转率的变化未因受体表达的变化而得到补偿。地西泮的性别特异性发育影响此前已有描述，例如对雌性后代围产期皮质酮水平的选择性影响（26）。
