Yang Guo-Sheng, Wang Wei, Wang Yi-Min, Chen Zhao-Dian, Wang Shuo, Fang Jia-Jie
Department of Urology, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
Asian J Androl. 2006 Sep;8(5):569-75. doi: 10.1111/j.1745-7262.2006.00191.x. Epub 2006 Jun 5.
To investigate the effect of cocaine on apoptosis and caspase-3 activity in germ cells in male rats at different ages.
Cocaine hydrochloride was given (15 mg/kg body weight s.c.) to male Sprague-Dawley rats of 3 weeks (n = 8), 6 weeks (n = 8) and 12 weeks (n = 8) of age, daily for 28 Days. The serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (T) and estrogen (E2) were assayed, and the DNA fragmentation of germ cells was determined by gel eletronphoresis. The cell cycle, apoptosis and caspase-3 activity of germ cells were tested by flow cytometry.
After the 28-day cocaine treatment, testes weight of the 3-week-old rats, the testes and body weights of the 6-week-old rats were decreased significantly compared to those of their corresponding controls (P < 0.05). The serum level of T was decreased significantly in the 3-week-old and 6-week-old rats, and the serum level of PRL was also decreased significantly in 12-week-old rats compared to the controls (P < 0.05). In all the three cocaine-treated groups, the isolated DNA displayed a clear ladder pattern, especially in the 6-week old rats. The number of apoptosic germ cells increased significantly in 3- and 6-week-old rats treated with cocaine (P < 0.05). The caspase-3 activity in all three groups increased significantly compared to the controls (P < 0.05), especially in the 6-week-old rats.
Cocaine exposure for 28 Days leads to significant damage to male gonad and apoptosis elevation in testes of rats of different ages, especially in those of 6 weeks of age. The increase in caspase-3 activity might be a key pathway related to the early stage of apoptosis as the mechanism of cocaine-induced germ cell loss.
研究可卡因对不同年龄雄性大鼠生殖细胞凋亡及半胱天冬酶-3活性的影响。
将盐酸可卡因（15毫克/千克体重，皮下注射）给予3周龄（n = 8）、6周龄（n = 8）和12周龄（n = 8）的雄性斯普拉格-道利大鼠，每日给药，持续28天。检测血清中卵泡刺激素（FSH）、黄体生成素（LH）、催乳素（PRL）、睾酮（T）和雌激素（E2）水平，并通过凝胶电泳测定生殖细胞的DNA片段化。采用流式细胞术检测生殖细胞的细胞周期、凋亡及半胱天冬酶-3活性。
经过28天的可卡因处理后，与相应对照组相比，3周龄大鼠的睾丸重量、6周龄大鼠的睾丸和体重显著降低（P < 0.05）。3周龄和6周龄大鼠的血清T水平显著降低，12周龄大鼠的血清PRL水平与对照组相比也显著降低（P < 0.05）。在所有三个可卡因处理组中，分离的DNA呈现出清晰的梯状条带模式，尤其是在6周龄大鼠中。可卡因处理的3周龄和6周龄大鼠中，凋亡生殖细胞数量显著增加（P < 0.05）。与对照组相比，所有三组的半胱天冬酶-3活性均显著增加（P < 0.05），尤其是在6周龄大鼠中。
暴露于可卡因28天会导致不同年龄大鼠的雄性性腺受到显著损伤，睾丸凋亡增加，尤其是6周龄大鼠。半胱天冬酶-3活性的增加可能是与凋亡早期相关的关键途径，作为可卡因诱导生殖细胞丢失的机制。
