脂质运载蛋白型前列腺素D合成酶水平在1型发作性睡病患者日间过度嗜睡中的作用研究

doi:10.12114/j.issn.1007-9572.2020.00.636

摘要/Abstract

摘要： 背景　前列腺素D2（PGD2）通过其受体DP1诱导腺苷生成，发挥强效促眠效果。近年来研究显示发作性睡病患者存在PGD2-DP1通路异常，合成PGD2的脂质运载蛋白型前列腺素D合成酶（L-PGDS，中枢系统PGD2关键合成酶）可能参与了该类患者日间过度嗜睡（EDS）的调节。目的　探讨1型发作性睡病患者脑脊液（CSF）和血清L-PGDS水平的变化，以及L-PGDS在EDS中的作用。方法　选取2013年12月—2015年12月北京大学人民医院睡眠中心收治的79例1型发作性睡病患者为研究对象（NT1组），选取同期就诊北京大学人民医院行腿部手术接受蛛网膜下腔阻滞麻醉（腰麻）的47例患者作为对照组。NT1组进行日间多次睡眠潜伏期试验（MSLT），计算睡眠潜伏期（SL）及睡眠起始快速眼动睡眠（SOREMPs）次数；两组均检测血清L-PGDS，CSF L-PGDS、HCRT水平及HLA-DQB1*0602表型。结果　两组年龄、性别、BMI和HLA-DQB1*0602阳性比例比较，差异有统计学意义（P<0.05）。对照组CSF HCRT水平高于NT1组，CSF（P=0.029）和血清（P<0.001）L-PGDS水平低于NT1组。NT1组、对照组CSF L-PGDS水平与CSF HCRT均无相关性（NT1组：rs=-0.160，P=0.159；对照组：rs=-0.179，P=0.229）。对照组（rs=0.358，P=0.014）和NT1组（rs=0.267，P=0.017）年龄与CSF L-PGDS水平均呈正相关。年龄与血清L-PGDS水平无相关关系（对照组：rs=-0.251，P=0.088，NT1组：rs=-0.058，P=0.612）。CSF L-PGDS及血清L-PGDS与BMI均无相关关系（CSF L-PGDS：对照组：rs=-0.097，P=0.521，NT1组：rs=0.122，P=0.283；血清L-PGDS：对照组：rs=-0183，P=0.223，NT1组：rs=0.188，P=0.098）。对NT1组和对照组年龄、性别及BMI进行1∶1匹配，获得了12组配对样本。匹配后，NT1组CSF L-PGDS及血清L-PGDS水平高于对照组（P<0.05）。结论　I型发作性睡病患者的血清和CSF L-PGDS水平较对照组明显增高，提示L-PGDS在EDS发病机制中发挥重要的作用。

关键词: 过度嗜睡性障碍, 发作性睡病, 前列腺素, 脂质运载蛋白型前列腺素D合成酶, 下丘脑激素类

Abstract: Background　Prostaglandin D2 （PGD2） induces adenosine production through its receptor DP1 to produce a strong hypnotic effect.Recent studies have showed alteration of PGD2-DP1 pathway in narcolepsy patients and the key enzyme for PGD2 synthesis in central nervous system，lipocalin-type prostaglandin D synthase （L-PGDS），has been suggested to be involved in process of excessive daytime sleepiness in type 1 narcolepsy（NT1）.Objective　This study is to explore the levels of L-PGDS in cerebral spinal fluid （CSF） and peripheral circulation of NT1 patients，and the role of L-PGDS in EDS.Methods　Eligible participants were recruited from Peking University People's Hospital during December 2013 to December 2015，including 79 NT1 patients（NT1 group） who visited the Sleep Medicine Center，and 47（control group） who underwent leg surgery under spinal anesthesia.All NT1 patients finished multiple sleep latency test，with mean sleep latency and number of sleep-onset rapid eye movement periods during the test were calculated.CSF and serum L-PGDS levels，CSF hypocretin level and HLA-DQB1*0602 phenotype were measured in both groups.Results　Significant differences between two groups were observed in age，sex ratio，mean BMI，and the rate of HLA-DQB1*0602 positivity（P<0.05）.CSF hypocretin level in control group was higher than that in NT1 group（P<0.001）.Moreover，CSF L-PGDS was much lower in the control group （P=0.029），and so was the serum L-PGDS（P<0.001）.No correlations between CSF L-PGDS and CSF hypocretin were found in neither control group（rs=-0.179，P=0.229） nor NT1 group（rs=-0.160，P=0.159）.A significant positive correlation was noticed between age and CSF L-PGDS levels in both control group（rs=0.358，P=0.014） and NT 1 group（rs=0.267，P=0.017）.Such correlation was absent between age and serum L-PGDS（control group：rs=-0.251，P=0.088；NT1 group：rs=-0.058，P=0.612）.No correlations were observed between CSF L-PGDS and BMI（control group：rs=-0.097，P=0.521；NT1group：rs=0.122，P=0.283） and between serum L-PGDS and BMI（control group：rs=-0183，P=0.223；NT1 group：rs=0.188，P=0.098）.In a subgroup of 12 age-，gender- and BMI-matched pairs，CSF and serum L-PGDS levels remained higher in NT1 patients than in controls（P<0.05，respectively）.Conclusion　NT1 patients had elevated CSF and serum L-PGDS levels，suggesting L-PGDS may play an important role in the physiopathological process of excessive daytime sleepiness.

Key words: Disorders of excessive somnolence, Narcolepsy, Prostaglandins, L-PGDS, Hypothalamic hormones

王配配,闫涵,李清华,等. 脂质运载蛋白型前列腺素D合成酶水平在1型发作性睡病患者日间过度嗜睡中的作用研究[J]. 中国全科医学, 2020, 23(35): 4454-4458. DOI: 10.12114/j.issn.1007-9572.2020.00.636.
WANG Peipei,YAN Han,LI Qinghua, et al. The Role of Lipocalin Type Prostaglandin D Synthase in Excessive Daytime Sleepiness in Patients with Narcolepsy Type 1[J]. Chinese General Practice, 2020, 23(35): 4454-4458. DOI: 10.12114/j.issn.1007-9572.2020.00.636.

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