养血柔肝复方改善睡眠剥夺所致糖脂代谢异常的作用及肝内生物钟基因Per所介导的机制研究

睡眠不足、不规律是困扰现代人群（医生、警察、军人等轮班工作人群）健康和生命质量的重要疾患，也是代谢类疾病形成的重要危险因素，现有的治疗方式大多直接靶向中枢神经递质但疗效有限。中医传统理论提出 “人卧则血归于肝”，提示睡眠与肝的密切联系。结合“肝藏血、主疏泄”的脏象理论，我们提出从肝论治，探索养血柔肝复方治疗睡眠剥夺引起的糖脂代谢紊乱的可能性和机制。我们的临床研究发现，养血柔肝复方有效改善患者睡眠情况；动物研究发现养血柔肝复方有效改善睡眠剥夺小鼠的糖脂代谢水平，且伴随肝脏组织结构的变化和肝内生物钟基因Per的显著变化。近年来诸多高水平研究指出肝内生物钟基因广泛参与肝脏免疫、代谢等功能的调节。基于此，本课题拟运用睡眠剥夺小鼠模型明确肝内Per基因参与介导养血柔肝复方改善睡眠剥夺小鼠糖脂代谢紊乱的作用及分子机制，为养血柔肝复方治疗睡眠剥夺引起的糖脂代谢紊乱提供新的理论和实验依据。

Sleep deprivation and irregularity are important health and quality of life problems for the modern population (doctors, police, military, etc.) and are also important risk factors for the formation of metabolic diseases. Traditional Chinese medicine theory proposes that "if a person lies down, the blood returns to the liver", suggesting the close connection between sleep and liver. Combined with the theory of "Liver harbors blood, main drainage", we propose to treat the liver and explore the possibility and mechanism of Yangxue Rougan Compound to treat the disorders of glycolipid metabolism caused by sleep deprivation. Our clinical studies have found that Yangxue Rougan Compound effectively improves patients' sleep; animal studies have found that Yangxue Rougan Compound effectively improves glycolipid metabolism levels in sleep-deprived mice, accompanied by changes in liver tissue structure and significant changes in the intrahepatic biological clock gene Per. In recent years, a number of high-level studies have shown that biological clock genes in the liver are widely involved in the regulation of liver immune and metabolic functions. Based on this, we propose to clarify the role and molecular mechanism of the intrahepatic Per gene in ameliorating the disorders of glycolipid metabolism in sleep-deprived mice by using a sleep-deprived mouse model, and provide a new theoretical and experimental basis for the treatment of disorders of glycolipid metabolism caused by sleep deprivation with Yangxue Rougan Compound.