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Objective: To explore the new mechanisms of tamoxifen(TAM)in the treatment for patients with idiopathic oligoasthenospermia—antioxidation.Methods: In a prospective,randomized,controlled clinical trial,120 cases of idiopathic oligoasthenospermia were enrolled and randomly assigned to the indomethacin group(n=60)treated with indomethacin(25 mg,bid)and TAM group(n=60)treated with TAM(10 mg,bid)for 3 months.Before and after treatment,we evaluated semen parameters,serum malonaldehyde(MDA)and total antioxidant capacity(TAC),seminal plasma MDA and TAC,spermatozoa intracellular reactive oxygen species(ROS),sperm succinate dehydrogenase(SDH)activity,sperm mitochondrial membrane potential(MMP)and sperm adenosine triphosphate(ATP)content.The independent t-test and one-way repeated measures analysis of variance(ANOVA)were used to compare the variables between and within two groups.Results: In the indomethacin group,the percentage of progressive motile sperms,total motility,sperm MMP and ATP content were increased significantly after 3 months treatment(P<0.05).In the TAM group,total sperm count,sperm concentration,the percentage of progressive motile sperms,total motility,serum and seminal plasma TAC,sperm MMP and ATP content were significandy improved or increased(P<0.05),while spermatozoa intracellular ROS was significantly decreased(P<0.05).Compared to the indomethacin group,TAM treatment showed better improvement in total sperm count,sperm concentration,serum TAC,seminal plasma TAC,spermatozoa intracellular ROS and sperm SDH activity.Conclusions: TAM treatment can significantly improve sperm quality,which is achieved through alleviating oxidative stress,improving sperm mitochondrial functionality,and subsequently increasing sperm motility.