模拟睡眠对脓毒症患者生物钟基因Bmal1、Per2表达和免疫功能、短期临床转归的影响

Effect of Simulated Sleep on the Expression of Circadian Clock Genes Bmal1,Per2,Immune Function,and Short-term Clinical Outcomes in Patients with Sepsis

【目的】探讨模拟睡眠对脓毒症患者生物钟基因脑-骨骼肌ARNT样基因1(Bmal1)、周期基因2(Per2)表达和免疫功能、短期临床转归的影响。【方法】80例脓毒症患者,随机分为对照组(常规对症治疗)和观察组(常规对症治疗联合模拟睡眠干预),每组40例。比较两组患者治疗前及治疗7 d后炎症因子[白细胞介素-6(IL-6)、IL-8、肿瘤坏死因子-α(TNF-α)和C反应蛋白(CRP)]、Bmal1和Per2表达水平、免疫功能、序贯器官衰竭评估评分(SOFA)、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)及机械通气时间、EICU住院时间和28 d病死率。【结果】两组治疗7 d后IL-6、IL-8、TNF-α、CRP均较治疗前降低(P<0.05),且观察组各指标低于对照组(P<0.05);两组Bmal1、Per2 mRNA表达较治疗前升高(P<0.05),且观察组上述指标高于对照组(P<0.05);两组CD4^(+)、CD4^(+)/CD8^(+)较治疗前升高(P<0.05),CD8^(+)较治疗前降低(P<0.05),且观察组CD4^(+)、CD4^(+)/CD8^(+)高于对照组(P<0.05),CD8^(+)低于对照组(P<0.05);两组SOFA评分和APACHEⅡ评分较治疗前降低(P<0.05),且观察组低于对照组(P<0.05)。观察组机械通气时间、EICU住院时间短于对照组(P<0.05);观察组28 d病死率低于对照组,但差异无统计学意义(P>0.05)。【结论】模拟睡眠能改善脓毒症患者生物钟基因Bmal1、Per2节律异常情况,增强免疫功能,减轻患者全身炎症反应,改善短期临床转归。

【Objective】To explore the effect of simulated sleep on the expression of circadian clock genes Brain and Muscle ARNT-Like 1(Bmal1)and Period 2(Per2),immune function,and short-term clinical outcomes in patients with sepsis.【Methods】Eighty sepsis patients were randomly divided into the control group(with standard symptomatic treatment)and the observation group(with standard symptomatic treatment combined with simulated sleep intervention),with 40 patients in each group.The study compared the levels of inflammatory factors[interleukin-6(IL-6),IL-8,tumor necrosis factor-alpha(TNF-α),and C-Reactive Protein(CRP)],Bmal1 and Per2 expression,immune function,Sequential Organ Failure Assessment(SOFA)score,Acute Physiology and Chronic Health EvaluationⅡ(APACHEⅡ)score,mechanical ventilation duration,ICU stay duration,and 28-day mortality rate between the two groups before treatment and 7 days after treatment.【Results】After 7 days of treatment,both groups showed reduced levels of IL-6,IL-8,TNF-α,and CRP compared to before treatment(P<0.05),with the observation group presenting even lower levels than the control group(P<0.05).Both groups exhibited increased expression of Bmal1 and Per2 mRNA(P<0.05)after 7 days of treatment compared to before treatment,with higher expression of Bmal1 and Per2 in the observation group than the control group(P<0.05).The levels of CD4^(+),CD4^(+)/CD8^(+)increased,while CD8^(+)decreased in both groups compared to before treatment(P<0.05),and the observation group showed higher CD4^(+),CD4^(+)/CD8^(+)and lower CD8^(+)than the control group(P<0.05).Both groups had reduced SOFA and APACHEⅡscores compared to before treatment(P<0.05),with lower scores in the observation group(P<0.05).The observation group had shorter mechanical ventilation and ICU stay durations(P<0.05),but the difference in 28-day mortality rate was not statistically significant between the two groups(P>0.05).【Conclusion】Simulated sleep can improve the dysregulation of circadian clock genes Bmal1 and Per2 in sepsis patients,enhance immune function,reduce systemic inflammatory response,and improve short-term clinical outcomes.