男性生殖道炎症可影响精子发生，导致精子成熟障碍。左卡尼汀（LC）可改善炎症对精子成熟的抑制作用,LC的主要转运蛋白为OCTN2,然而OCTN2如何介导炎症影响精子成熟尚不清楚。Toll样受体4（TLR4）介导的先天免疫和TGF-β/BMPs介导的免疫平衡对维持精子免疫屏障尤为重要。已有报道OCTN2含PDZ结合域，并能够与PDZK1相互作用。PDZK1可通过调节PLC-β3/STAT5信号而调节TGF-β信号。我们前期研究表明LPS/TLR4信号抑制OCTN2，LPS大鼠实验中TGF-β1表达明显降低。据此，我们推测LPS可通过抑制OCTN2调控TGF-β/BMPs,降低TGF-β信号,使免疫微环境调控失败,精子成熟障碍;我们通过在LPS大鼠模型过表达OCTN2和LC干预进行验证OCTN2的作用机制。本研究将对炎症通路转归的理解以及阐明炎症导致精子成熟障碍的机制具有重要的意义。

Influence of male reproductive tract inflammation on spermatogenesis result in dysfunction of sperm maturation. L-carnitine(LC) had a improve role to the procdure of sperm maturation and its transporter, organic cation transporter2(OCTN2), mediated inflammation influence on sperm maturation, but the mechanism remains elusive.Innate immunity mediated by TLR4 and immune balance mediated by TGF-β/BMPs are particularly important to maintain immunologic barrier of sperm.Previous studies suggested that OCTN2 contains PDZ domain-containing 1 (PDZK1) and certified that OCTN2 can interact with PDZK1.PLC-β3 pathway can be regulated by PDZK1 and active STAT5 to inhibit the TGF-β pathway. Our preliminary studies suggested that OCTN2 was down-rgulated by LPS/TLR4 signal and the expresion of TGF-β1 was significantly decreased when LPS effect in rats. Accordingly,we hypothesized thatLPS can derease TGF-β/BMPs signal by inhibiting OCTN2 ,resulted in regulatory failures of immuno-microenvironment and dysfunction of sperm maturation.In order to verify mechanism of OCTN2,the overexpression of OCTN2 and LC intervention would be proceeded in rats with LPS effected.This study would have a significant sense of theory to understand inflammatonry normal outcomes and reactivation, and to clarify the mechanisim influencing sperm maturation;It also posesses great amplication value to the clinical treatment of infertility.