重度阻塞性睡眠呼吸暂停低通气综合征患者血清缺氧诱导因子-1α和胰岛素样生长因子-1及脑源性神经营养因子与认知功能的关系

Relationship between hypoxia-inducible factor-1α,insulin-like growth factor-1,brain-derived neurotrophic factor and the cognitive function of patients with severe obstructive sleep apnea hypopnea syndrome

目的:探讨缺氧诱导因子-1α(HIF-1α)、胰岛素样生长因子-1(IGF-1)及脑源性神经营养因子(BDNF)在重度阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血清中的变化及与认知功能改变的关系。方法:纳入经多导睡眠监测确诊OSAHS的患者67例(OSAHS组),同时选取17例健康人作为对照组。运用蒙特利尔认知评估量表(MoCA)对其进行认知功能评估,根据分值分为认知功能正常组(MoCA≥26)及认知功能异常组(MoCA<26),采用酶联免疫吸附法测定血清中HIF-1α、IGF-1及BDNF水平。结果:OSAHS组共筛查出MCI 20例,对照组无认知功能异常者,两组比较差异有统计学意义(P<0.05)。对照组与认知功能正常组比较HIF-1α、IGF-1存在差异(分别P<0.05和P<0.01),BDNF、BMI无明显差异(P>0.05);对照组与认知功能异常组比较HIF-1α、BDNF存在差异(均P<0.05),IGF-1、BMI无明显差异(P>0.05);认知功能正常组与异常组比较IGF-1、BDNF存在明显差异(分别P<0.01和P<0.05),HIF-1α、BMI无明显差异(P>0.05)。认知功能正常组血清BDNF与IGF-1呈正相关(r=0.663,P<0.01),BDNF与HIF-1α呈正相关(r=0.562,P<0.01),IGF-1与HIF-1α呈正相关(r=0.657,P<0.01);三者分别与AHI、MoCA及BMI比较无明显相关(P>0.05)。认知功能异常组血清BDNF与MoCA呈正相关(r=0.304,P<0.05);其余各因素相互间无明显相关性(P>0.05)。结论:①重度OSAHS患者与健康人比较存在轻度认知障碍;②重度OSAHS认知功能正常者的血清HIF-1α、IGF-1及BDNF三者水平密切相关,认知功能异常者的血清HIF-1α、IGF-1及BDNF三者水平无明显相关;③血清HIF-1α、IGF-1及BDNF三种物质可能共同参与并维持机体正常认知功能,IGF-1、BDNF对机体认知功能变化较为敏感。

Objective： To explore the change of hypoxia-inducible factor-1α, insulin-like growth factor-1, brain-derived neurotrophic factor in serum in patients with severe obstructive sleep apnea hypopnea syndrom and their relationship with cognitive function change. Method：Sixty-seven cases of patients diagnosed with OSAHS by polysomnography were defined as OSAHS group,while 17 cases of healthy people as control group. Montreal cog- nitive assessment scale （MoCA） was employed to assess the cognitive function,and accordingly the subjects were divided into normal cognitive function group （MoCA≥26） and abnormal group （MoCA〈26）. The level of HIF- 1α,IGF-1 and BDNF in serum were detected by enzyme-linked immunosorbent （ELISA）. Result： Twenty cases with mild cognitive impairment （MCI）were screened in severe OSAHS group, and no case with cognitive impairment in the control group （P〈0.05）. Compared between the control group and normal cognitive function group, significant differences were found in the level of H1F-1（P〈0.05） and IGF-1 （P〈0.01）, and no significant differences were found in that of BDNF and BMI （P〉0.05）. Compared between the control group and abnormal cognitive function group, significant differences were found in the level of HIF-1α and BDNF （P〈0.05）, and no significant differences were found in that of IGF-1 and BMI （P〉0.05）. Compared between normal and abnormal cognitive function group, significant differences were found in the level of IGF-1 （P〈0. 01） and BDNF （P〈 0.05）, and no significant differences were found in that of HIF-1α and BMI （P〉0.05）. In normal cognitive function group, the level of serum BDNF was positively correlated with that of IGF-1 （r=0. 663,P〈0.01） and HIF- 1α（r=0. 562, P〈0.01）, respectively ; and the level of IGF-1 was positively correlated with that of HIF-1α（r= 0. 657 ,P〈0. 01）. However, there were no correlation between the level of BDNF,IGF-1 ,and HIF-1α and that of AHI, BMI and MoCA score, respectively （P〉0.05）. In the abnormal cognitive function group,the level of serum BDNF were positively related to that of MoCA （r=0. 304,P〈0. 05）, and there were no correlation between the rest factors（P〉0.05）. Conclusion：（1） Compared with healthy people, the severe OSAHS patients exist mild cognitive impairment;（2） In patients with severe OSAHS, the level of serum HIF-1α, IGF-1 and BDNF were closely correlated in the normal cognitive function group, while those were not correlated in the abnormal cognitive function group; （3）The serum HIF-1α,IGF-1 and BDNF may jointly engage in and maintain normal cognitive function; and IGF-1 ,BDNF are sensitive to the changes of cognitive function.