Liu Lu, Zhang Li, Li Longjiang, Chen Mengting, Wang Zhe, Shen Yi, Huang Jiayi, Tang Ling
Department of Rehabilitation Medicine and Physical Therapy, The Affiliated Rehabilitation Hospital of Chongqing Medical University, 50 Xiejiawan Cultural Seventh Village, Jiulongpo District, Chongqing, 400050, China.
Department of Pathophysiology, Chongqing Medical University, 1 Yixueyuan Road, Chongqing, 400016, China.
Inflamm Res. 2020 Nov;69(11):1133-1142. doi: 10.1007/s00011-020-01393-3. Epub 2020 Aug 18.
Sleep loss is common in patients with liver injury, but the effects of sleep deprivation (SD) on liver injury remain unclear. In the present study, the potential effects of SD on acute liver injury and the underlying mechanisms have been investigated.
The sleep of male BALB/c mice has been deprived by using a modified multiple platform water bath for 3 days and acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). The degree of liver injury was detected by aminotransferase determination, histopathology and survival rate analysis. Inflammatory response and melatonin (MT) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, hepatocyte apoptosis was determined by caspase activity measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
We observed that SD increased plasma aminotransferases, TUNEL-positive hepatocytes, histological abnormalities and mortality rates in mice with LPS/D-Gal treatment. SD also promoted LPS/D-Gal-induced production of TNF-α and upregulated hepatic caspase-8, caspase-9, and caspase-3 activities in LPS/D-Gal-exposed mice. In addition, SD significantly decreased MT contents in plasma of mice with acute liver injury, but supplementation with MT reversed these SD-promoted changes.
Our data suggested that SD exacerbated LPS/D-Gal-induced liver injury via decreasing melatonin production.
睡眠不足在肝损伤患者中很常见，但睡眠剥夺（SD）对肝损伤的影响仍不清楚。在本研究中，研究了SD对急性肝损伤的潜在影响及其潜在机制。
使用改良的多平台水浴剥夺雄性BALB/c小鼠的睡眠3天，并通过腹腔注射脂多糖（LPS）和D-半乳糖胺（D-Gal）诱导急性肝损伤。通过测定转氨酶、组织病理学和生存率分析来检测肝损伤程度。通过酶联免疫吸附测定（ELISA）测量炎症反应和褪黑素（MT）。此外，通过测量半胱天冬酶活性和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）试验来确定肝细胞凋亡。
我们观察到，在接受LPS/D-Gal治疗的小鼠中，SD增加了血浆转氨酶、TUNEL阳性肝细胞、组织学异常和死亡率。SD还促进了LPS/D-Gal诱导的TNF-α产生，并上调了LPS/D-Gal暴露小鼠肝脏中半胱天冬酶-8、半胱天冬酶-9和半胱天冬酶-3的活性。此外，SD显著降低了急性肝损伤小鼠血浆中的MT含量，但补充MT可逆转这些由SD促进的变化。
我们的数据表明，SD通过减少褪黑素的产生加剧了LPS/D-Gal诱导的肝损伤。
