Wang Chao-Yung, Hsieh Ming-Jer, Hsieh I-Chang, Shie Shian-Sen, Ho Ming-Yun, Yeh Jih-Kai, Tsai Ming-Lung, Yang Chia-Hung, Hung Kuo-Chun, Wang Chun-Chieh, Wen Ming-Shien
Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
Department of Cardiology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
Biochem Biophys Res Commun. 2016 Sep 16;478(2):935-41. doi: 10.1016/j.bbrc.2016.08.054. Epub 2016 Aug 9.
Polymicrobial sepsis is a potentially fatal condition and a significant burden on health care systems. Acute lung injury is the most common complication of sepsis and results in high mortality. However, there has been no recent significant progress in the treatment of sepsis or acute lung injury induced by sepsis. Here we show that mice deficient in the circadian protein CLOCK had better survival than wild-type mice after induction of polymicrobial sepsis by cecal ligation and puncture. Inflammatory cytokine production was attenuated and bacterial clearance was improved in CLOCK-deficient mice. Moreover, acute lung injury after induction of sepsis was significantly decreased in CLOCK-deficient mice. Genome-wide profiling analysis showed that inhibin signaling was reduced in CLOCK-deficient mice. These data establish the importance of circadian CLOCK-inhibin signaling in sepsis, which may have potential therapeutic implications.
多微生物败血症是一种潜在的致命疾病，给医疗保健系统带来沉重负担。急性肺损伤是败血症最常见的并发症，死亡率很高。然而，败血症或败血症引起的急性肺损伤的治疗最近并没有取得重大进展。在这里，我们表明，通过盲肠结扎和穿刺诱导多微生物败血症后，缺乏昼夜节律蛋白CLOCK的小鼠比野生型小鼠具有更好的存活率。CLOCK缺陷小鼠的炎性细胞因子产生减少，细菌清除改善。此外，CLOCK缺陷小鼠在诱导败血症后的急性肺损伤明显减少。全基因组分析表明，CLOCK缺陷小鼠中抑制素信号传导减少。这些数据证实了昼夜节律CLOCK-抑制素信号传导在败血症中的重要性，这可能具有潜在的治疗意义。
