School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.
Zhejiang Famous Chinese Medicine Clinic, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Aging (Albany NY). 2024 Feb 28;16(5):4541-4562. doi: 10.18632/aging.205607.
Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.14, 20.27, 40.54 g/kg;) or estradiol valerate (0.15 mg/kg), ovarian function, oxidative stress (OS) and protein expression of Sirt1/p53 were evaluated. For experiments, H2O2 (200 μM) was used to treat KGN to construct ovarian granulosa cells (OGCs) cell senescence model. Pretreatment with NTZF (1.06 mg/mL) or p53 inhibitor (Pifithrin-α, 1 μM) was performed before induction of senescence, and further evaluated the cell senescence, OS, mRNA and protein expression of Sirt1/p53. , NTZF improved ovarian function, alleviated OS and Sirt1/p53 signaling abnormalities in POI mice. experiments showed that NTZF reduced the level of OS and alleviated the senescence of H2O2-induced KGN. In addition, NTZF activated the protein expression of Sirt1, inhibited the mRNA transcription and protein expression of p53 and p21. Alleviating OGCs senescence and protecting ovarian function through Sirt1/p53 is one of the potential mechanisms of NTZF in the treatment of POI.
宁心通郁滋肾方（NTZF）是一种治疗卵巢早衰（POI）的临床经验方，其潜在机制尚不清楚。在实验中，通过皮下注射 D-半乳糖（D-gal，200mg/kg）构建 POI 小鼠模型（C57BL/6 小鼠）。用 NTZF（10.14、20.27、40.54g/kg）或戊酸雌二醇（0.15mg/kg）治疗后，评估卵巢功能、氧化应激（OS）和 Sirt1/p53 蛋白表达。在实验中，用 H2O2（200μM）处理 KGN 构建卵巢颗粒细胞（OGCs）衰老模型。在诱导衰老前用 NTZF（1.06mg/mL）或 p53 抑制剂（Pifithrin-α，1μM）预处理，进一步评估细胞衰老、OS、Sirt1/p53 的 mRNA 和蛋白表达。NTZF 改善了 POI 小鼠的卵巢功能，减轻了 OS 和 Sirt1/p53 信号异常。实验表明，NTZF 降低了 OS 水平，减轻了 H2O2 诱导的 KGN 衰老。此外，NTZF 激活了 Sirt1 蛋白表达，抑制了 p53 和 p21 的 mRNA 转录和蛋白表达。通过 Sirt1/p53 减轻 OGCs 衰老并保护卵巢功能是 NTZF 治疗 POI 的潜在机制之一。
