甾体5α-还原酶抑制剂LTZ-8和类似物的筛选及其抗前列腺增生作用(英文)

The screening and anti-prostatic hyperplasia activity assessment of novel steroid 5α-reductase inhibitors LTZ-8 and others

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 。

AIM To screen new anti-prostatic hyperplasia drugs LTZ-8 an d others(testosterone derivatives with different groups at C-3, C-4 and C-17) , which are different structures of steroid 5α-reductase inhibitors. METHODS Isotope screening method was used to determine the ability o f LTZ-8 to inhibit steroid 5α-reductase in vitro. Healthy male ra ts, which were castrated and injected testosterone to induce the regrowth of gla ndular cells, were selected as animal model. LTZ-8 was given orally once a day (3, 10 and 30 mg·kg -1 ) for 30 d. Wet and dry prostate weight was quantifi ed and morphological structures of prostate were detected under light microscope . RESULTS LTZ-1, LTZ-5, LTZ-6 and LTZ-8 showed inhibitory effec t on the activity of 5α-reductase,and LTZ-8 was the most effective one 〔K i=(21.0± 2.2)nmol·L -1 〕. Both the wet and dry prostate we ight was reduced by 82% and 86% in LTZ-8 treated group (30 mg·kg -1 ) compared with control group respectively (P&lt;0.05). Prostatic glandular cell height and acinar luminal area were decreased by LTZ-8 treatment in a dose-dep endent manner. CONCLUSION LTZ-8 inhibits steroid 5α-reductase activity in vitroand blocks the prostatic hyperplasia in testostero ne-induced castrated rats.