哇巴因与弱精子症关系的研究进展

Ouabain and asthenospermia

弱精子症在男性不育因素中约占30%。目前临床上针对弱精子症尚缺乏特异性治疗药物。探讨弱精子症发病机制,对开发弱精子症特异性治疗药具有重要意义。成熟睾丸组织以及成熟精子尾部均特异性存在Na^+/K^+-ATP酶α4亚型(Na^+/K^+-ATPaseα4 isoform,NKA4)的蛋白,该蛋白缺失或活性下降可使精子活力明显下降。哇巴因是NKA4的天然抑制剂,能特异性结合NKA4上的哇巴因位点来抑制NKA4的活性。人体下丘脑和肾上腺皮质均能分泌哇巴因样甾体激素,称为内源性哇巴因(EO)。EO与弱精子症发病有一定联系,其机制可能是通过抑制精子NKA4的活性继发影响精子的Na^+/H^+交换、Na^+/Ca^(2+)交换以及精子细胞膜电位,最终使精子活动率下降。

Asthenospermia accounts for about 30% of the causes of male infertility. Currently,most drugs for asthenospermia lack specificity and desirable therapeutic efficiency. An insight into the pathogenesis of asthenospermia is important for the development of specific therapies for this disease. The protein Na^＋/ K^＋- ATPase α4 isoform（ NKA4） presents in both mature testis tissue and the sperm tail,the absence or reduced activity of which may significantly decrease sperm motility. Ouabain is a natural inhibitor of NKA4,suppressing its activity by specifically binding the ouabain site in it. The hypothalamus and adrenal cortex excrete an ouabain-like steroid hormone called endogenous ouabain（ EO）,which may be associated with the pathogenesis of asthenospermia by inhibiting the activity of NKA4,affecting Na^＋/ H^＋exchange,Na^＋/ Ca^2＋ exchange and sperm cell membrane potential,and eventually reducing sperm motility.