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目的 为筛选新的不同结构的甾体 5α 还原酶抑制剂LTZ 8等抗前列腺增生药物 (在C 3,C 4,C 1 7具有不同基团的睾酮衍生物 )。方法 同位素筛选法检测LTZ 8对体外 5α 还原酶的抑制能力。体内动物模型选用去势大鼠 (注射丙酸睾酮刺激前列腺重新生长 ) ,连续灌胃LTZ 8(3 ,1 0及 30mg·kg-1 ,每日 1次 ) 30d ,检测前列腺组织绝对重量和相对重量 ,并对前列腺上皮进行组织形态学分析。结果 LTZ 1 ,LTZ 5,LTZ 6和LTZ 8均有抑制 5α 还原酶的作用 ,其中LTZ 8的作用最强〔Ki=(2 1 .0±2 .2 )nmol·L-1 〕。大鼠口服 30mg·kg-1 LTZ 8,前列腺湿重和干重分别为对照组的 82 %和 86% (P <0 .0 5)。前列腺上皮细胞高度和腺腔面积呈剂量依赖性下降。结论 LTZ 8具有抑制 5α 还原酶的活性 ,并能抑制去势大鼠注射丙酸睾酮引起的前列腺增生
The aim is to screen for new anti-benign prostatic hyperplasia drugs (testosterone derivatives with different groups in C 3, C 4, C 1 7) such as steroid 5α reductase inhibitor LTZ 8 with different structures. Methods The isotope screening method was used to determine the inhibitory effect of LTZ 8 on 5α-reductase in vitro. In vivo animal models were castrated rats (injected with testosterone propionate to stimulate the prostate regrowth), continuous administration of LTZ 8 (3,1 and 30 mg · kg-1, once a day) 30d, the absolute weight of prostate tissue and relative Weight, and histopathological analysis of the prostate epithelium. Results LTZ 1, LTZ 5, LTZ 6 and LTZ 8 all inhibited the action of 5α-reductase, and the effect of LTZ 8 was the strongest (Ki = (21 ± 0.2) nmol·L-1〕. Rats were given 30 mg · kg -1 LTZ 8 orally, and the wet weight and dry weight of the prostate were 82% and 86% of those in the control group (P <0.05). Prostate epithelial cells height and luminal area in a dose-dependent decline. Conclusion LTZ 8 has inhibitory activity on 5α-reductase and inhibits benign prostatic hyperplasia in ovariectomized rats