昼夜节律紊乱诱导的氧化应激在绝经后心血管功能中枢调控中的作用及其机制

The incidence of cardiovascular disease in postmenopausal women is significantly increased, and is closely related to oxidative stress and sympathetic output hyperfunction in the rostral ventrolateral medulla (RVLM). The study suggests that circadian rhythm disorder is an important factor in inducing cardiovascular disease. However, it is not clear that the central regulation and mechanism of the circadian rhythm disorder on postmenopausal cardiovascular and sympathetic activities. Therefore, the objective of this project is to clarify the role and mechanism of circadian rhythmic disorder in the regulation of postmenopausal oxidative stress and sympathetic nerve activity. On the basis of menopausal rats, we will be clear: (1) the role and significance of postmenopausal circadian rhythm disorder on sympathetic nerve activity and cardiovascular function; (2) the role and significance of postmenopausal circadian rhythm disorder on the central role of oxidative stress; (3) the role of the estrogen replacement therapy on the central oxidative stress and sympathetic hyperfunction induced by circadian rhythm disorder. The result of this study provides a new theory and prevention strategy for the abnormal cardiovascular function of postmenopausal women in the circadian rhythm disorder.

绝经后女性心血管疾病的发生率明显升高，并与交感中枢头端延髓腹外侧区（RVLM）内的氧化应激和交感输出亢进密切相关。研究提示昼夜节律紊乱是诱发心血管疾病的一个重要因素。但目前并不清楚昼夜节律紊乱对绝经后心血管和交感活动的中枢调控作用和机制。因此，本项目的研究目标是明确昼夜节律紊乱对绝经后中枢氧化应激和交感神经活动调控中的作用及机制。在绝经大鼠模型基础上，我们将明确：（1）绝经后昼夜节律紊乱对交感神经活动和心血管功能的作用特点和意义；（2）绝经后昼夜节律紊乱对中枢氧化应激的作用和机制；（3）雌激素替代治疗对昼夜节律紊乱诱导的中枢氧化应激和交感亢进中的作用。本课题的结果为昼夜节律紊乱对绝经后女性心血管功能异常提供新的理论和防止策略。

绝经后女性心血管疾病的发生率升高与交感中枢头端延髓腹外侧区（RVLM）内氧化应激增强和交感输出亢进密切相关。研究提示昼夜节律紊乱是诱发心血管疾病的一个重要因素。但目前并不清楚昼夜节律紊乱对绝经后心血管和交感活动的中枢调控作用和机制。在绝经大鼠模型基础上，进行昼夜节律紊乱，我们明确了（1）OVX组大鼠血压、RSNA和血浆中NE浓度显著增加，而昼夜节律紊乱一周后，OVX大鼠这些指标进一步增加；（2）绝经后昼夜节律紊乱对交感神经活动和血压的效应与RVLM中抗氧化蛋白Nrf2和HO-1表达下调，导致氧化应激增强相关；（3）补充雌激素可改善OVX和节律紊乱引起的大鼠血压、RSNA、血浆中NE和RVLM中ROS含量增加，并且与E2增加RVLM中Nrf2和HO-1蛋白表达相关。以上研究结果表明绝经后昼夜节律紊乱可加重RVLM内氧化应激水平，补充E2可上调抗氧化蛋白Nrf2和HO-1表达，减轻氧化应激，从而改善绝经后昼夜节律紊乱导致的交感亢进和高血压。本项目重点关注绝经后昼夜节律紊乱对RVLM调控交感神经活动功能的影响和作用机制，为更好的防治绝经女性心血管疾病提供了新的策略。