Curcumin Alleviates Bisphenol A‑Induced Blood-Testis Barrier Disruption in Mice by Targeting Surfactant Protein B (SFTPB) to Suppress Oxidative Stress-Activated NLRP3 Inflammasome

Bisphenol A (BPA), a globally prevalent industrial chemical,
significantly
harms the male reproductive health. Curcumin has anti-inflammatory,
antioxidation, and antiapoptosis pharmacological properties, but the
effect and mechanism of curcumin against BPA-induced testicular damage
are still unknown. This study investigates the protective effect of
curcumin against Bisphenol A (BPA)-induced blood-testis barrier (BTB)
injury in mice. BPA exposure caused oxidative stress, activated the
NOD-like receptor protein 3 (NLRP3) inflammasome in Sertoli cells,
and disrupted BTB integrity. Curcumin treatment alleviated these effects
by reducing oxidative stress and inhibiting NLRP3 activation. We identified
Surfactant Protein B (SFTPB) as a key target, finding that curcumin
directly interacts with and down-regulates it. Functionally, SFTPB
knockdown mimicked curcumin’s protection, while its overexpression
exacerbated BPA-induced damage. Our findings demonstrate that curcumin
mitigates BPA-induced testicular injury by targeting SFTPB to suppress
the oxidative stress-NLRP3 pathway, revealing a novel mechanism for
the therapeutic action of curcumin.

双酚A（Bisphenol A, BPA）是一种全球广泛分布的工业化学品，可对男性生殖健康造成显著损害。姜黄素具备抗炎、抗氧化及抗凋亡的药理特性，但其对抗双酚A诱导的睾丸损伤的作用与机制仍未明确。本研究探究了姜黄素对双酚A诱导的小鼠血睾屏障（blood-testis barrier, BTB）损伤的保护作用。双酚A暴露可引发氧化应激，激活支持细胞（Sertoli cells）中的NOD样受体蛋白3（NOD-like receptor protein 3, NLRP3）炎症小体，并破坏血睾屏障的完整性。姜黄素给药可通过减轻氧化应激、抑制NLRP3激活缓解上述损伤。我们鉴定出表面活性蛋白B（Surfactant Protein B, SFTPB）为关键靶点，发现姜黄素可直接与其结合并下调其表达。功能实验显示，敲低SFTPB可模拟姜黄素的保护作用，而过表达SFTPB则会加重双酚A诱导的损伤。本研究结果表明，姜黄素可通过靶向SFTPB抑制氧化应激-NLRP3通路，从而缓解双酚A诱导的睾丸损伤，揭示了姜黄素治疗作用的全新机制。