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环氧化酶抑制剂长期治疗对雄性大鼠生殖参数的影响。

Effect of chronic treatment with a cyclooxygenase inhibitor on reproductive parameters in male rat.

作者信息

Saeed Sheikh A, Anwar Naheed, Khan Khalid M, Sarfraz Noorjehan

机构信息

Department of Biological & Biomedical Sciences, Aga Khan University, Karachi, Pakistan.

出版信息

J Ayub Med Coll Abbottabad. 2009 Jul-Sep;21(3):66-71.

Abstract

BACKGROUND

Indomethacin is a member of non-steroidal anti-inflammatory drugs (NSAIDs) commonly used for treatment of gout, arthritis, and other inflammatory conditions. It has been shown to inhibit ovarian prostaglandins synthesis in mammals, birds, fish and reptiles. However, the effects of its chronic administration on male reproductive functions remain largely unknown. Using rat as a model, we studied the effect of chronic treatment with indomethacin on the male reproductive system.

METHODS

Testosterone was measured in the serum, testicular tissue, and testicular interstitial fluid by radioimmunoassay. Moreover, we also studied the direct effect of indomethacin in vitro on luteinizing hormone stimulated testosterone secretion from the Leydig cells isolated from various treatment groups.

RESULTS

Indomethacin treatment for 50 days caused a significant but reversible decrease in prostate weight, epididymal sperm reserves and sperm motility score compared with control rats (p < 0.05). In vitro stimulation of Leydig cells isolated from treated rat's testes with luteinizing hormone (250 microIU) produced significantly reduced testosterone compared with cells from control groups (p < 0.05). Furthermore, stimulatory effect of luteinizing hormone on the control Leydig cells was significantly reduced when these cells were challenged with luteinizing hormone in the presence of indomethacin, (p < 0.05). Testosterone concentration in the testicular tissue and testicular interstitial fluid reduced after indomethacin treatment (p < 0.05).

CONCLUSION

Due to its significant inhibition of key reproductive hormones, indomethacin effectively inhibits reproductive functions if used on a long-term basis. In his study, we have identified potential risks in the long-term use ofcyclooxygenase inhibitors.

摘要

背景

吲哚美辛是非甾体抗炎药(NSAIDs)的一种,常用于治疗痛风、关节炎和其他炎症性疾病。研究表明,它能抑制哺乳动物、鸟类、鱼类和爬行动物卵巢中前列腺素的合成。然而,其长期给药对雄性生殖功能的影响仍 largely 未知。我们以大鼠为模型,研究了吲哚美辛长期治疗对雄性生殖系统的影响。

方法

采用放射免疫分析法测定血清、睾丸组织和睾丸间质液中的睾酮水平。此外,我们还研究了吲哚美辛在体外对从不同治疗组分离的睾丸间质细胞中促黄体生成素刺激的睾酮分泌的直接影响。

结果

与对照大鼠相比,吲哚美辛治疗50天导致前列腺重量、附睾精子储备和精子活力评分显著但可逆地降低(p < 0.05)。与对照组细胞相比,用促黄体生成素(250微国际单位)体外刺激经治疗大鼠睾丸分离的睾丸间质细胞产生的睾酮显著降低(p < 0.05)。此外,当在吲哚美辛存在下用促黄体生成素刺激对照睾丸间质细胞时,促黄体生成素对这些细胞的刺激作用显著降低(p < 0.05)。吲哚美辛治疗后睾丸组织和睾丸间质液中的睾酮浓度降低(p < 0.05)。

结论

由于其对关键生殖激素的显著抑制作用,吲哚美辛长期使用会有效抑制生殖功能。在本研究中,我们确定了长期使用环氧化酶抑制剂的潜在风险。

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