Saiyed M, Riker W K
Department of Pharmacology, School of Medicine, Oregon Health Sciences University, Portland.
J Pharmacol Exp Ther. 1993 Mar;264(3):1146-53.
We examined central and peripheral components of cholinergic drug protection against hypoxia in male and female mice. Survival times were measured in groups of control and treated (i.p. injection) animals exposed to hypoxia (5% O2/95% N2). Body temperatures were also measured in separate groups of normoxic control and treated animals. Control (NaCl) animals of both sexes survived only 3.5 and 3.7 min of hypoxia. After physostigmine (0.2 mg/kg), however, significantly more females (82.4%) than males (40.5%) survived 35 to 60 min of hypoxia, although physostigmine hypothermia was equal in both sexes. Pilocarpine (5 mg/kg) also produced a gender difference (female > male) in survival, despite equal hypothermia. Hypothermia after neostigmine (0.2 mg/kg) was equal in males and females, yet neither sex survived longer than controls. The protective and hypothermic effects of physostigmine were blocked by atropine sulphate (5 mg/kg). In contrast, atropine methylnitrate (2 mg/kg) did not block physostigmine hypothermia in either sex, but markedly decreased physostigmine's protective effect in females. Beside the significant gender differences in physostigmine and pilocarpine protection, the results show that hypothermia alone is not responsible for protection or for the gender difference. Survival prolongation in males appears to depend solely on physostigmine's central actions. In females, peripheral actions (e.g., hormone release from pituitary and ovary) may contribute to protection and to the gender difference.
我们研究了胆碱能药物对雄性和雌性小鼠缺氧保护的中枢和外周成分。在暴露于低氧环境（5% O₂/95% N₂）的对照组和处理组（腹腔注射）动物中测量存活时间。还在常氧对照组和处理组的单独动物组中测量体温。两性的对照（氯化钠）动物在低氧环境中仅存活3.5分钟和3.7分钟。然而，给予毒扁豆碱（0.2 mg/kg）后，存活35至60分钟的雌性（82.4%）明显多于雄性（40.5%），尽管毒扁豆碱引起的体温降低在两性中是相同的。毛果芸香碱（5 mg/kg）在存活方面也产生了性别差异（雌性>雄性），尽管体温降低程度相同。新斯的明（0.2 mg/kg）引起的体温降低在雄性和雌性中相同，但两性的存活时间均未长于对照组。毒扁豆碱的保护作用和体温降低作用可被硫酸阿托品（5 mg/kg）阻断。相比之下，硝酸甲基阿托品（2 mg/kg）在两性中均未阻断毒扁豆碱引起的体温降低，但显著降低了毒扁豆碱对雌性的保护作用。除了毒扁豆碱和毛果芸香碱保护作用存在显著性别差异外，结果表明单纯的体温降低并非保护作用或性别差异的原因。雄性存活时间的延长似乎仅取决于毒扁豆碱的中枢作用。在雌性中，外周作用（例如，垂体和卵巢释放激素）可能有助于保护作用和性别差异。
