Dose-effect relationship between androgen and neural protection in neonatal rats with hypoxic-ischemic brain damage and adverse effects of androgen / 中华儿科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore brain-protective effect of androgen, its dose-effect relationship and long-term adverse reaction.</p><p><b>METHOD</b>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 learning and 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.</p><p><b>RESULT</b>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 (1(st) 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, 1(st) 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, 1(st) 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.</p><p><b>CONCLUSION</b>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.</p>