基于静息态功能核磁共振观察天王补心丹加减方对功能性便秘伴情绪障碍的影响

Effect of Modified Tianwang Buxin Dan on Functional Constipation with Mood Disorder Based on Resting State Functional Magnetic Resonance Imaging

目的探讨天王补心丹加减方对功能性便秘(FC)患者便秘症状、情绪障碍及血清5-羟色胺(5-HT)、P物质(SP)和血管活性肠肽(VIP)水平的影响,并采用静息态功能核磁共振(fMRI)观察治疗前后患者脑功能的变化特征。方法选取2021年8月至2022年3月于江苏省中医院肛肠科门诊就诊的阴虚肠燥型FC患者70例,随机分为治疗组与对照组各35例(对照组脱落5例,治疗组脱落6例)。对照组予聚乙二醇散剂口服治疗,治疗组使用天王补心丹加减方口服治疗,2组疗程均为8周。治疗前后观察2组患者中医临床症状及体征(包括排便间隔、排便困难程度、大便性状等)变化,并使用汉密尔顿抑郁量表(HAMD)和汉密尔顿焦虑量表(HAMA)、90项症状自评量表(SCL-90)评估患者情绪及心理状态变化。随机抽取40例患者(治疗组21例、对照组19例)进行大脑静息态fMRI扫描,分析大脑低频震荡振幅(ALFF)的变化特征。结果治疗后,2组患者中医临床症状及体征均明显改善(P<0.05,P<0.01),HAMD、HAMA、SCL-90中抑郁及焦虑因子评分显著改善(P<0.05),治疗组优于对照组(P<0.05,P<0.01);2组血清5-HT、SP水平均较治疗前明显升高(P<0.05),血清VIP水平均明显降低(P<0.05),治疗组优于对照组(P<0.05)。经fMRI扫描发现,治疗后2组负责情绪调节的前扣带回、眶额回、海马脑活动降低,负责躯体感觉及控制运动的辅助运动区、中央前回的脑区活动增加(P<0.01),此外,治疗组在情绪唤醒网络和下丘脑-垂体-肾上腺(HPA)轴相关的内侧前额叶皮层、杏仁核、下丘脑等脑区也存在活动减少(P<0.01)。结论天王补心丹加减方在缓解FC患者便秘症状的同时,还能改善其抑郁及焦虑评分,其机制可能与调节负责情绪、躯体感觉以及HPA轴等脑区的活动相关。

OBJECTIVE To investigate the effects of modified Tianwang Buxin Dan on constipation symptoms,mood disorders,serum 5-HT,substance P(SP)and vasoactive intestinal peptide(VIP)levels in patients with functional constipation,and to observe the changes in brain function of patients before and after treatment with resting state functional magnetic resonance imaging(fMRI).METHODS A total of 70 functional constipation patients with Yin deficiency and intestinal dryness and treated at the proctology department of Jiangsu Provincial Hospital of Traditional Chinese Medicine from August 2021 to March 2022 were randomly divided into a treatment group and a control group,with 35 cases each(5 cases dropped out of the control group and 6 cases dropped out of the treatment group).The control group was orally treated with polyethylene glycol powder,and the treatment group was orally treated with modified Tianwang Buxin Dan.The course of treatment for both groups was 8 weeks.Before and after treatment,the changes in TCM clinical symptoms and signs(including defecation interval,defecation difficulty level,and faces characteristics)of the two groups of patients were observed,and the Hamilton depression scale(HAMD),Hamilton anxiety scale(HAMA),and symptom checklist-90(SCL-90)were adopted to evaluate the emotional and psychological state changes of the patients.Forty patients(21 patients in the treatment group and 19 patients in the control group)were randomly selected for brain resting state fMRI to analyze the characteristics of the amplitude of low-frequency fluctuations(ALFF).RESULTS After treatment,the TCM clinical symptoms and signs in both groups of patients were significantly improved(P<0.05,P<0.01),the HAMD score,HAMA score,and depression and anxiety factors in SCL-90 were significantly improved(P<0.05),the therapeutic efficacy of the treatment group was superior to the control group(P<0.05,P<0.01).The levels of serum 5-HT and SP in both groups were significantly higher than those before treatment(P<0.05),and the content of serum VIP was significantly reduced(P<0.05),with the treatment group demonstrating better improvement(P<0.05).fMRI scanning showed that after treatment,the brain activity of the anterior cingulate gyrus,orbitofrontal gyrus and hippocampus responsible for emotional regulation in the two groups decreased,and the brain activity of the auxiliary motor area responsible for somatic sensation and motor control and the precentral gyrus increased(P<0.01).In addition,in the treatment group,decreased activity in the medial prefrontal cortex,amygdala,hypothalamus and other brain regions related to the emotional arousal network and hypothalamus pituitary adrenal(HPA)axis was noticed(P<0.01).CONCLUSION The modified Tianwang Buxin Dan can not only alleviate the constipation symptoms of functional constipation patients,but also improve depression and anxiety scores.The mechanism may be related to regulating the activities of brain regions responsible for emotion,somatic sensation and HPA axis.