Objective To explore brain-protective effect of androgen, its dose-effect relationship and long-term adverse reaction. Method Seventy two 3-day-old SD rats were randomized into androgen group( n = 32) , HIBD model group ( n = 32 ) and sham operated group ( n = 8 ). The androgen group and HIBD model group were further randomized into 30 mg/kg group, 60 mg/kg group, 120 mg/kg group and 240 mg/kg group, respectively. In androgen group and HIBD group, every rat was given testosterone or peanut oil, one time a day. Three days later, HIBD model was established by occlusion of the left common carotid artery and inhalation of 8% oxygen plus 92% nitrogen for 2.5 hours. Adult rats' ability of learningand memory was determined by water maze test. Escape latencies were recorded and analyzed by statistics.Vaginal cells of all female rats were examined everyday for identifying their estrous cycle. Female rats were allowed to live with normal adult male rats if the female rats were in estrous period. Vaginal cells were examined everyday until sperm was seen, which was the signal of gestation. Pregnancy rate and the number of embryos were recorded and analyzed by statistics. Acropetal coefficient was calculated. The testes and epididymis were taken from adult male rats, histopathological sections were made, and the structure of testis and epididymis were studied under light microscope. Result In Morris experiment, escape latencies (EL)of HIBD group were much longer than those of sham operation group( 27.71 ± 3.19)s, time of first enter target ( 1st ET) was later than that of sham operation group(5.34 ±0.83)s, times of target cross (TC) was less than that of sham operation group ( 18.88 ± 1.89 ) ( P ＜ 0.01, P = 0. 0005 ). EL of androgen group (34.89 ± 3.68,33.71 ± 3.38,33.84 ± 3.45, 35.43 ± 2.43 ) were much shorter than that of HIBD group,1st ET (5.39 ± 1.51,6.28 ±2.07,5.09 ± 1.61, 5.85 ±0.87)was earlier than that of HIBD group, TC ( 12.75 ± 2.05,14.88 ± 3.36,14.88 ± 2.36,14.38 ± 1.60) was more than that of HIBD group ( P ＜ 0.01,P=0.0001). Among the four doses groups of androgen group, EL, 1st ET and TC had no statistical significance (P ＞0.05, P =0.159). There were no statistical significance between male rats of androgen group [Testes acropetal coefficient ( 0.89 ± 0.07,0.92 ± 0.08, 0.88 ± 0.11,0.87 ± 0.09 ), epididymis acropetal coefficient ( 0.25 ± 0.02,0.24 ± 0.05,0.26 ± 0.04,0.23 ± 0.05 )], HIBD group and sham operation group( P ＞ 0.05, P = 3.207 ). Among the four doses groups of androgen group had no statistical significance ( P ＞ 0.05, P = 6.663 ). There were no statistical significance between female rats of androgen group( pregnancy rate, 100%; times, 14.52 ± 3.34,14.69 ± 2.28,14.98 ± 2. 67, 15.38 ± 3.07 ), HIBD group and sham operation group in pregnancy rate and times. Conclusion The intellectual ability of rats decreased after HI. Androgen could reduce the effect of HI on intellectual ability. Androgen had no adverse reaction to the reproductive capacity of adult rats.%目的 探讨雄激素对HIBD新生大鼠脑保护作用及量效关系,初步揭示雄激素的远期副作用.方法 3日龄SD大鼠72只随机分为:假手术组(n=8)、HIBD对照组(n=32)、雄激素组(n=32).雄激素组和HIBD对照组各分为4个剂量组,每个剂量组8只.3日龄时雄激素组每个剂量组每只大鼠分别腹腔注射30 mg/kg、60 mg/kg、120 mg/kg和240 mg/kg的丙酸睾酮,HIBD对照组每个剂量组每只大鼠腹腔注射相应毫升数的花生油,每日1次,连续3 d.7日龄时雄激素组和HIBD对照组制作HIBD模型.所有动物饲养至成年后进行水迷宫实验以测定空间学习记忆能力;成年雌鼠每日做阴道涂片,明确每只大鼠的完整发情周期,对于处于发情期的雌鼠及时与雄鼠合笼,次日晨雌鼠做阴道细胞涂片检查,并观察有无阴栓,以查到精子或观察到阴栓作为受孕成功标志,记录各组雌鼠的妊娠率以及妊娠胚胎数目,进行统计学处理,比较组间差异.计算成年雄鼠睾丸系数和附睾系数.结果 水迷宫实验中,HIBD对照组较假手术组平均潜伏期(27.71±3.19)s和首次穿越平台时间(5.34±0.83)s明显延长,HIBD对照组较假手术组穿越目标象限次数(18.88±1.89)明显减少,均有统计学意义(P均＜0.01,P=0.0005＝.雄激素组中各相应剂量组平均潜伏期(34.89±3.68,33.71±3.38,33.84±3.45,35.43±2.43)和首次穿越平台时间(5.39±1.51,6.28±2.07,5.09±1.61,5.85±0.87)较HIBD对照组明显缩短,穿越目标象限次数(12.75±2.05,14.88±3.36,14.88±2.36,14.38±1.60)较HIBD对照组明显增加,均有统计学意义(P均＜0.01,P=0.0001＝.雄激素组各剂量组以上指标相比均无统计学意义(P均＞0.05,P=0.159).雄激素各剂量组雄性大鼠睾丸系数(0.89 ±0.07,0.92±0.08,0.88±0.11,0.87±0.09)和附睾系数(0.25±0.02,0.24±0.05,0.26±0.04,0.23 ±0.05)与假手术组和HIBD组相比,差异均无统计学意义(P＞均0.05,P=3.207),雄激素组各剂量组间相比无统计学差异(P＞0.05,P=6.663);雄激素各剂量组雌性大鼠的怀孕率(均100%)及妊娠胚胎数(14.52±3.34,14.69±2.28,14.98±2.67,15.38±3.07)与假手术组和HIBD组相比,差异均无统计学意义(P＞0.05,P=5.085).结论 HIBD对大鼠的空间学习记忆能力有影响,可降低其空间学习记忆能力.雄激素干预后可明显降低HIBD对大鼠学习记忆能力的影响.雄激素的早期干预对成年后大鼠的生殖能力无影响.
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