Department of Gynecology, Huzhou Maternity & Child Health Care Hospital, Huzhou, Zhejiang 313000, China.
Department of Gynaecology, Lishui Hospital of Traditional Chinese Medicine, Lishui, Zhejiang 323000, China.
Reprod Biol. 2023 Jun;23(2):100763. doi: 10.1016/j.repbio.2023.100763. Epub 2023 Apr 17.
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder. Sitagliptin (Sit) and rosiglitazone (Ros) are widely used to treat PCOS, but the mechanism is unclear. This study explored the mechanism that Sit and Ros inhibited autophagy and inflammation in PCOS. In this study, 50 female SD rats were divided into 5 groups (n = 10): control, PCOS, Sit, Ros, and Sit+Ros group. The body weight and ovarian weight were measured 2 h after the last administration, and fasting blood glucose, insulin levels were determined. Lipid metabolism and pathological changes were detected by an automatic biochemical analyzer and HE staining. Sex hormone, oxidative stress and inflammatory levels were detected by ELISA. PCR detected IL-18, TNF-α, IL-6, IL-1β, ATG3, and ATG12 mRNA. The PI3K/AKT/mTOR, TLR4/NF-κB pathway and autophagy-related proteins were detected by western blot. Finally, the number of autophagolysosomes was detected by transmission electron microscopy. Sit or Ros alone reduced body weight, ovarian weight, fasting blood glucose, and insulin levels in PCOS rats. It also improved lipid metabolism, sex hormone levels, oxidative stress and pathological changes, restored the estrous cycle, and corpus luteum quantity. In addition, it could reduce the levels of IL-18, TNF-α, IL-6, IL-1β, ATG3, and ATG12 mRNA, inhibit the expression of Beclin1, LC3, PI3K/AKT/mTOR, and TLR4/NF-κB pathway proteins. The Sit+Ros group was more effective than single administration. In conclusion, Sit+Ros inhibited the PI3K/AKT/mTOR, TLR4/NF-κB pathways, thereby inhibiting the autophagy and inflammation of PCOS rats, which will provide a theoretical basis for PCOS.
多囊卵巢综合征（PCOS）是一种常见的内分泌和代谢紊乱。西他列汀（Sit）和罗格列酮（Ros）被广泛用于治疗 PCOS，但作用机制尚不清楚。本研究探讨了 Sit 和 Ros 抑制 PCOS 自噬和炎症的机制。在这项研究中，将 50 只雌性 SD 大鼠分为 5 组（n=10）：对照组、PCOS 组、Sit 组、Ros 组和 Sit+Ros 组。末次给药后 2h 测量体重和卵巢重量，检测空腹血糖和胰岛素水平。通过自动生化分析仪和 HE 染色检测脂代谢和病理变化。通过 ELISA 检测性激素、氧化应激和炎症水平。PCR 检测 IL-18、TNF-α、IL-6、IL-1β、ATG3 和 ATG12 mRNA。Western blot 检测 PI3K/AKT/mTOR、TLR4/NF-κB 通路和自噬相关蛋白。最后，通过透射电子显微镜检测自噬溶酶体的数量。单独使用 Sit 或 Ros 可降低 PCOS 大鼠的体重、卵巢重量、空腹血糖和胰岛素水平。还改善了脂代谢、性激素水平、氧化应激和病理变化，恢复了发情周期和黄体数量。此外，它可以降低 IL-18、TNF-α、IL-6、IL-1β、ATG3 和 ATG12 mRNA 的水平，抑制 Beclin1、LC3、PI3K/AKT/mTOR 和 TLR4/NF-κB 通路蛋白的表达。Sit+Ros 组的效果优于单独给药。总之，Sit+Ros 抑制了 PI3K/AKT/mTOR、TLR4/NF-κB 通路，从而抑制了 PCOS 大鼠的自噬和炎症，为 PCOS 提供了理论依据。
