睡眠呼吸暂停所致的相关障碍性免疫损伤对雌性大鼠生殖系统的影响研究
The Impact of Sleep Apnea Induced Immune Dysfunction on the Reproductive System of Female Rats
王筝 1张栋 1高志华1
作者信息
- 1. 300350 天津市，天津大学海河医院妇产科 天津市呼吸疾病研究所
- 折叠
摘要
背景 睡眠呼吸暂停（OSA）是临床高发的睡眠障碍性疾病，随生活方式改变发病率持续攀升，可引发心血管、代谢等多系统损伤。近年发现女性睡眠呼吸暂停患者常出现月经紊乱、不孕等生殖功能异常，但睡眠呼吸暂停诱导雌性生殖系统损伤的免疫调控机制，尤其是树突状细胞（DCs）介导的免疫应答异常的作用，仍缺乏深入解析。目的 研究睡眠呼吸暂停所致的相关障碍性免疫损伤对雌性大鼠生殖系统的影响。方法 2023—2024年，将30只动情周期规律的4~6月龄雌性SD大鼠随机分为空白对照组、短期组、长期组，各10只，空白对照组正常饲养6周；短期组正常饲养3周后，在制备睡眠呼吸暂停模型基础上饲养3周；长期组在制备睡眠呼吸暂停模型基础上饲养6周。分析各组大鼠动情周期，卵巢组织雌激素受体α亚型（ERα）、雌激素受体β亚型（ERβ）表达量，卵巢组织中卵泡数量；观察DCs迁徙能力、DCs刺激同种T淋巴细胞增殖反应（MLR）能力及DCs内Toll样受体4（TLR4）、RelB表达量变化。并分析各组大鼠生育力和子代小鼠生长发育情况。结果 与空白对照组比较，长期组动情周期紊乱率升高（P<0.05）。与空白对照组比较，短期组、长期组卵巢组织ERα、ERβ表达量降低（P<0.05）；与短期组比较，长期组卵巢组织ERα、ERβ表达量降低（P<0.05）。与空白对照组比较，短期组、长期组原始卵泡、初级卵泡、窦状卵泡数目降低，闭锁卵泡数目增加（P<0.05）；与短期组比较，长期组原始卵泡、初级卵泡、窦状卵泡数目降低，闭锁卵泡数目增加（P<0.05）。与空白对照组比较，短期组、长期组DCs迁徙比例降低，MLR升高（P<0.05）；与短期组比较，长期组DCs迁徙比例降低，MLR升高（P<0.05）。与空白对照组比较，短期组、长期组DCs内TLR4、RelB表达量均升高（P<0.05）；与短期组比较，长期组DCs内TLR4、RelB表达量均升高（P<0.05）。与空白对照组比较，长期组妊娠率、活产率均降低（P<0.05）。3组活产子代小鼠出生21d每日体质量均有所升高，但与空白对照组比较，短期组与长期组生长迟滞，尤其是长期组。结论 睡眠呼吸暂停可引起雌性大鼠卵巢功能减退，降低生育力，推测其可能通过改变DCs迁徙能力来激活TLR4/RelB引起免疫损伤，从而导致生殖系统紊乱。
Abstract
Background Sleep apneaOSA is a high incidence sleep disorder disease in clinic. With the change of lifestylethe incidence rate continues to risewhich can cause cardiovascularmetabolic and other multi system damage. In recent yearsit has been found that female sleep apnea patients often experience reproductive dysfunction such as menstrual disorders and infertility. Howeverthe immune regulatory mechanism of sleep apnea induced damage to the female reproductive systemespecially the abnormal immune response mediated by dendritic cellsDCsstill lacks in-depth analysis. Thereforethis study is conducted. Objective To study the effects of sleep apnea induced immune dysfunction on the reproductive system of female rats. Methods The research period was from January 2023 to December 2024. Thirty 4-6 month old female SD rats with regular estrous cycles were randomly divided into a blank control groupa short-term groupand a long-term groupwith 10 rats in each group. The blank control group was fed normally for 6 weeksthe short-term group was fed for 3 weeks on the basis of preparing a sleep apnea modeland the long-term group was fed for 6 weeks on the basis of preparing a sleep apnea model. The estrous cycle of each group of ratsthe expression levels of estrogen receptor alphaER alpha and estrogen receptor betaER beta subtypes in ovarian tissueand the number of follicles in ovarian tissue were analyzed. the migration ability of DCsthe ability of DCs to stimulate homologous T lymphocyte proliferation responseMLRand the changes in toll like receptor 4 TLR4 and RelB expression levels in DCs were observed. The fertility of each group of rats and the growth and development of offspring mice were analyzed. Results Compared with the blank control groupthe long-term groups showed an increased rate of dysregulation in the estrous cycleP<0.05. Compared with the blank control groupthe expression levels of ER and ER in ovarian tissues were reduced in the short-term and long-term groupsP<0.05. Compared with the short-term groupthe long-term group showed a decrease in the expression levels of ER and ER in ovarian tissueP<0.05. Compared with the blank control groupthe number of primordial folliclesprimary folliclesand antral follicles decreased in the short-term and long-term groupswhile the number of blocked follicles increasedP<0.05. Compared with the short-term groupthe long term group showed a decrease in the number of primordial folliclesprimary folliclesand antral folliclesand an increase in the number of blocked folliclesP<0.05. Compared with the blank control groupthe migration rate of DCs decreased and the MLR increased in the short-term and long-term groupsP<0.05. Compared with the short-term groupthe long-term group showed a decrease in the migration rate of DCs and an increase in MLRP<0.05. Compared with the blank control groupthe expression levels of TLR4 and RelB in DCs in both the short-term and long-term groups increasedP<0.05. Compared with the short-term groupthe long-term group showed an increase in the expression levels of TLR4 and RelB in DCsP<0.05. Compared with the blank control groupthe pregnancy rate and live birth rate of long-term groups decreasedP<0.05. Three groups of live born offspring mice showed an increase in daily weight after 21 days of birthbut compared with the blank control groupthe short-term and long-term groups showed growth retardationespecially the long-term group. Conclusion Sleep apnea can cause ovarian dysfunction and reduced fertility in female ratssuggesting that it may activate TLR4/RelB by altering the migration ability of DCsleading to immune damage and reproductive system disorders.关键词
睡眠呼吸暂停/免疫损伤/生殖系统/卵巢功能引用本文复制引用
王筝,张栋,高志华.睡眠呼吸暂停所致的相关障碍性免疫损伤对雌性大鼠生殖系统的影响研究[EB/OL].(2026-03-19)[2026-03-21].https://chinaxiv.org/abs/202603.00107.学科分类
基础医学
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