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红醇通过增强Nrf2来缓解辐射引起的过早卵巢衰竭
Lingli Xin1,2, Fengsheng Li3, Huijie Yu3
1Department of Graduate Administration, General Hospital of Chinese PLA, Beijing, China.
American journal of reproductive immunology (New York, N.Y. : 1989)
|September 28, 2023
概括
霍诺基 (HKL) 通过抑制亡和热亡,防止辐射诱导的过早卵巢衰竭 (POF). 这项研究表明,在暴露于电离辐射 (IR) 后,HKL可提高生育能力和卵巢功能.
科学领域:
- 生殖生物学和毒理学.
- 瘤学和放射治疗的副作用
- 药理学和天然产品研究.
背景情况:
- 卵巢对辐射的敏感性在放射治疗患者中构成早期卵巢衰竭 (POF) 的重大风险.
- 电离辐射 (IR) 可以诱导卵巢损伤,影响生育能力和内分泌功能.
- 探索辐射保护剂对于减轻IR诱导的卵巢毒性至关重要.
研究的目的:
- 调查基醇 (HKL) 对电离辐射 (IR) 诱导的过早卵巢衰竭 (POF) 的辐射保护作用.
- 在小鼠模型中评估HKL预治疗对卵巢组织学,功能和生育能力的影响.
- 阐明HKL对红外线引起的卵巢损伤的保护作用背后的分子机制.
主要方法:
- 雌性C57BL/6小鼠被用Honokiol (HKL) 或载体治疗,然后暴露在3.2 Gy全身电离辐射 (IR) 中.
- 卵巢功能通过淋巴体指数 (GSI),血清激素水平 (E2,AMH),卵泡计数和生育测试 (活下来的后代) 来评估.
- 分子分析包括免疫组织化学,免疫光,TUNEL测定,西部斑点和qPCR来评估亡,烧亡和氧化应激标志物 (Nrf2,HO-1).
主要成果:
- IR显著诱导POF,其特点是卵泡数量减少,血清E2和AMH减少,GSI降低,生育能力受损.
- 在IR上调调节的前性 (Pho-P53,Bax,C-caspase-3) 和 pyroptotic (Pho-NF-κB p65,NLRP3,caspase-1) 蛋白质,同时降低了抗性Bcl-2.
- 预先治疗HKL (10 mg/kg) 有效地防止IR诱导的卵巢损伤,保持卵巢功能和生育能力,并增强Nrf2/HO-1表达.
结论:
- 红醇 (HKL) 显示出显著的辐射保护作用,防止电离辐射 (IR) 诱导的过早卵巢衰竭 (POF).
- 通过抑制亡和亡途径,HKL改善了IR诱导的卵巢损伤.
- 保护机制涉及Nrf2表达和转位的增强,这表明在抗氧化剂防御中发挥作用.
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