封堵器
血睾丸屏障
粘合连接
支持细胞
精子发生
糖尿病
紧密连接
医学
内分泌学
并行传输
内科学
化学
细胞生物学
生物
细胞
磁导率
生物化学
钙粘蛋白
膜
作者
Jingxun Wei,Xuanzhao Lu,Xiaowen Bao,Chi Zhang,Jiaqi Li,Chaoxing Ren,Zhiming Zhu,Beiting Ma,Nan Zhang,Xin Jin,Bo Ma
标识
DOI:10.1016/j.ejphar.2022.175430
摘要
Disruption of blood-testis barrier (BTB) was a crucial pathological feature of diabetes induced-testicular injury at early phase. Aucubin (AU), a main active component in Eucommiae Cortex, has drawn attention for its benefits against male reproductive system disease. The current study was aimed at investigating the protective role of AU and exploring the underlying mechanism in diabetic model. A murine model of type 2 diabetes mellitus (T2DM) was induced by high-fat diet (HFD) combined with streptozocin (STZ). Testicular weight index and morphology, sperm quality, integrity of BTB and protein levels were analyzed. The underlying mechanism of the protective effect of AU was further explored in Sertoli cells (SCs) cultured with high glucose (HG). Our results showed AU inhibited testicular structural destruction, restored disruption of BTB and improved abnormal spermatogenic function in diabetic mice. Consistent with in vivo results, HG induced decreased transcellular resistance and increased permeability in SCs monolayers, while AU exposure reverses this trend. Meanwhile, reduced expression of Zonula occludin-1(ZO-1) and Connexin43(Cx43) in testicular tissue diabetic mice and HG-induced SCs was prominently reversed via AU treatment. Mechanistic studies suggested a high affinity interaction between AU and c-Src protein was identified based on molecular docking, and the activation of c-Src was significantly inhibited in AU treatment. Furthermore, AU significantly increased the expression of Cx43 and ZO-1 proteins HG-induced SCs, which can be further enhanced in gene-silenced c-Src cells to some extent. Our results suggested that AU ameliorated disruption of BTB and spermatogenesis dysfunction in diabetic mice via inactivating c-Src to stabilize cell junction integrity.
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