雷公藤中雄性抗生育化合物的筛选和药效研究

SCREENING AND PHARMACODYNAMIC STUDY OF MALE ANTIFERTILITY COMPOUNDS ISOLATED FROM TRIPTERYGIUM WILFORDII

本文报道了从雷公藤中分离所得290余个组分(化合物),经动物筛选后得到4个雄性抗生育有效化合物(T_4、T_9、TW_(13)及TW_(15)),其化学结构均已确定,属同一类物质,估计为植物代谢不同阶段的产物.用国际公认方法进行药效鉴定的结果表明,4药分别用50、100、30及200μg/kg/日灌胃给药,连续6～7周可使雄大鼠不育。此时,附睾精子密度.特别是活率.明显下降;而性行为.血清睾酮及机体各脏器均未见明显改变。T_9及TW_(15)使附睾肉毒碱明显减少。此外,也作了某些遗传及免疫学观察。本文表明,在所用剂量下。T_4、T_9、TW_(13)的主要靶细胞可能为附睾精子及变态期精子细胞,而TW_(15)则可损伤各级生精细胞及附睾精子。

In the screening of more than 290 components (compounds) isolated from Tripte- rygium wilfordii Hook. f., 4 compounds, T4, T9, TW13 and TW15, were shown to possess a potent male antifertility effect in rats. Their chemical structures were iden- tified and appeared to belong to the same category. Therefore, it is suggested that they may represent different stage products of plant metabolism. Employing internationally accepted assaying method, it was documented that these drugs given orally for 6-7weeks at dose levels of 50, 100, 30 and 200μg/kg per day, respectively, could cause infer- tility in male rats, At the same time, the sperm density in cauda epididymas, and particularly the sperm motility, were significantly decreased. The sex behavior, serum testosterone and the histology of somatic organs were apparently not affected. The epididymal carnitine level, as well as some genetic and immunological parameters were also assessed. Based on the findings in the testicular histology, and inepididymal sperm and carnitine values, the authors believe that at the doses employed, the main target cells of T4, T9 and TW13 are epididymal spermatozoa and metamorphosing spermatids, while TW15 may damage different stage spermatogenic cells (T4 and T9 were provided by the Institute of Dermatology, Chinese Academy of Medical Sciences, T15 by the China pharmaceutical University and TW 13 by the City University of London, U. K. The British Columbia University of Canada also provided additional amount of TW 13 and TW15).