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果糖-1,6-二磷酸锶可挽救腺嘌呤诱导的雄性性腺功能减退并上调睾丸内皮素-1系统。

Strontium fructose 1,6-diphosphate rescues adenine-induced male hypogonadism and upregulates the testicular endothelin-1 system.

作者信息

Feng Yu, Zhang Qi, Dai De-Zai, Ying Han-Jie, Dai Yin

机构信息

Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China.

出版信息

Clin Exp Pharmacol Physiol. 2007 Nov;34(11):1131-7. doi: 10.1111/j.1440-1681.2007.04693.x.

DOI:10.1111/j.1440-1681.2007.04693.x
PMID:17880366
Abstract
  1. Male hypogonadism is a major problem that starts to affect middle-aged men and has adversely effects on human sexual life. The aim of the present study was to investigate the effect of strontium fructose 1,6-diphosphate (FDP-Sr) on male hypogonadism in rats. 2. The pharmacological model of testis dysfunction was created by administration of adenine (200 mg/kg per day, i.g.) for 30 days. Three doses of FDP-Srs (200, 100 and 50 mg/kg per day, i.g.) were administered in parallel with adenine. Finally, mating behaviour index (the mounting latency and the number of mounting events), the total number of spermatozoa and sperm motility, related enzyme function and gene regulation and the mRNA levels of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), prepro-endothelin (ET)-1, endothelin-converting enzyme (ECE) and endothelin receptor A (ET(A)) were analysed. 3. The results showed that adenine significantly prolonged the mounting latency and decreased the number of mounting events, markedly reduced the total number of spermatozoa, slowed sperm motility and decreased testicular enzyme activity in the testes. At the mRNA level, adenine significantly downregulated serum testosterone, StAR, P450sc and 3beta-HSD. In parallel, adenine also targeted the ET-1 system, significantly downregulating mRNA levels of prepro-ET-1, ECE and ET(A). Administration of FDP-Sr dose-dependently reversed these effects. 4. In conclusion, adenine-induced testis dysfunction appears to be manifested as loss of sexual function in association with decreased spermatogenesis and reduced mRNA levels of steroidogenesis and the testicular ET-1 system. These abnormalities were significantly restored by FDP-Sr in a dose-dependent manner. These data indicate the possibility of using FDP-Sr to treat male hypogonadism.
摘要
  1. 男性性腺功能减退是一个主要问题,它开始影响中年男性,并对人类性生活产生不利影响。本研究的目的是探讨1,6 - 二磷酸果糖锶(FDP - Sr)对大鼠男性性腺功能减退的影响。2. 通过每天腹腔注射腺嘌呤(200毫克/千克)持续30天建立睾丸功能障碍的药理模型。与腺嘌呤同时给予三剂FDP - Sr(每天200、100和50毫克/千克,腹腔注射)。最后,分析交配行为指数(爬跨潜伏期和爬跨次数)、精子总数和精子活力、相关酶功能和基因调控以及类固醇生成急性调节蛋白(StAR)、细胞色素P450侧链裂解酶(P450scc)、3β - 羟基类固醇脱氢酶(3β - HSD)、前内皮素(ET)-1、内皮素转换酶(ECE)和内皮素受体A(ET(A))的mRNA水平。3. 结果表明,腺嘌呤显著延长了爬跨潜伏期并减少了爬跨次数,明显减少了精子总数,减缓了精子活力并降低了睾丸中的睾丸酶活性。在mRNA水平上,腺嘌呤显著下调血清睾酮、StAR、P450sc和3β - HSD。同时,腺嘌呤还靶向ET - 1系统,显著下调前ET - 1、ECE和ET(A)的mRNA水平。给予FDP - Sr可剂量依赖性地逆转这些作用。4. 总之,腺嘌呤诱导的睾丸功能障碍似乎表现为性功能丧失,伴有精子发生减少以及类固醇生成和睾丸ET - 1系统的mRNA水平降低。这些异常通过FDP - Sr以剂量依赖性方式得到显著恢复。这些数据表明使用FDP - Sr治疗男性性腺功能减退的可能性。

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