基于静息态功能核磁共振成像研究针刺对早发性卵巢功能不全患者下丘脑功能连接的影响

Effect of acupuncture on hypothalamic functional connectivity in patients with premature ovarian insufficiency based on resting-state functional magnetic resonance imaging

目的:基于静息态功能核磁共振成像(rs-fMRI)比较早发性卵巢功能不全(POI)患者与健康志愿者下丘脑与全脑脑区的功能连接差异,探讨针刺治疗POI的中枢机制。方法:以12例POI患者为针刺组,12例健康志愿者为健康对照组。穴组1取百会、中脘、神庭等穴,穴组2取双侧肾俞、次髎,针刺组予两穴组交替针刺治疗,30min/次,3次/周(2次穴组1,1次穴组2),共治疗12周;健康对照组不进行任何干预。于治疗前后通过改良Kupperman指数量表(KI)、焦虑自评量表(SAS)评价患者状态;微粒子化学发光法检测两组受试者血清卵泡刺激素(FSH)、促黄体生成素(LH)、雌二醇(E_(2))、抗苗勒管激素(AMH)含量;B超检测窦卵泡计数(AFC);针刺组患者与健康志愿者分别在针刺治疗前后和入组后行rs-fMRI检查,以双侧下丘脑为感兴趣区,观察POI患者与健康志愿者的下丘脑与全脑脑区的功能连接差异以及针刺前后POI患者的下丘脑与全脑脑区的功能连接变化。结果:针刺组治疗前KI、SAS评分高于健康对照组(P<0.01),与治疗前比较,治疗后FSH、LH含量降低,KI、SAS评分降低,AFC增加(P<0.05)。与健康志愿者比较,POI患者左侧下丘脑与左侧中央沟盖、右侧枕中回、左侧中央旁小叶功能连接强度增高,与左侧豆状核苍白球功能连接强度降低(P<0.05);右侧下丘脑与左侧海马、左侧中央旁小叶、右侧中央沟盖功能连接强度增高,与右额上回功能连接强度降低(P<0.05)。与治疗前比较,针刺组POI患者治疗后右侧下丘脑与左侧额下回、右侧额下回、左侧岛叶功能连接强度增高,与左侧直回功能连接强度降低(P<0.05)。结论:下丘脑与全脑脑区的功能连接异常可能是POI患者发病的中枢因素之一。针刺可改善POI患者的卵巢功能及临床症状,其机制可能与调节下丘脑与多个脑区的功能连接有关。

Objective To compare the differences in functional connectivity(FC)between the hypothalamus and whole brain regions in patients with premature ovarian insufficiency(POI)and healthy volunteers based on resting-state functional magnetic resonance imaging(rs-fMRI)and investigate the mechanism of acupuncture on treatment of POI.Methods Twelve POI patients were recruited to the acupuncture group and 12healthy volunteers to the control group.Patients in the acupuncture group received acupuncture at two groups of acupoints alternatively,including Baihui(GV20),Zhongwan(CV12),Shenting(GV24),Shenshu(BL23),Ciliao(BL32)and so on,30min once time,3times per week for 12weeks.The state of patients was evaluated by modified Kupperman Index(KI)and self-rating anxiety scale(SAS).Follicle-stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E_(2)),and anti-mullerian hormone(AMH)were tested by microparticle-based chemiluminescence.B ultrasonography was used to detect the antral follicle count(AFC).Meanwhile,POI patients and healthy volunteers underwent the rs-fMRI examination before and after acupuncture treatment and after enrollment,respectively.With hypothalamus as the region of interest,the differences in FC between the hypothalamus and other brain regions in POI patients and healthy volunteers and the changes of FC between the hypothalamus and whole brain regions in POI patients before and after acupuncture were observed.Results The SAS and KI scores of pre-treatment POI patients were higher than those in the control group(P<0.01).In comparison with those pre-treatment,FSH,LH,and SAS and KI scores of POI patients decreased after treatment,while AFC increased(P<0.05).Compared with the control group,the FC of the left hypothalamus with left central sulcus,right middle occipital gyrus,and left paracentral lobule increased,but decreased with left globus pallidus of the lenticular nucleus in POI patients.Furthermore,the FC of the right hypothalamus with the left hippocampus,the left para-central lobule,and the right central sulcus increased,while the FC between the right hypothalamus and the right superior frontal gyrus decreased(P<0.05).For the acupuncture group,compared with the conditions before treatment,the FC of the right hypothalamus with the left inferior frontal gyrus,the left insula,and right inferior frontal gyrus was strengthened,but weakened with the left gyrus rectus(P<0.05).Conclusion The abnormal FC between the hypothalamus and whole brain regions may be one of the central pathological factors of POI.Acupuncture can improve the ovarian function and clinical symptoms of patients with POI,which may be related to its effect in regulating the FC between the hypothalamus and multiple brain regions.