包春辉^１，汪　迪^１，刘　鹏^２，施　茵^１，金小明^３，吴璐一^１，曾晓清^４，张建业^５，刘慧荣^１，吴焕淦^１

（1 上海市针灸经络研究所针灸免疫研究室，上海　200030；，2 西安电子科技大学生命科学与技术学院，陕西西安　710071；3  Stark Neurosciences Research Institute，Indiana University School of Medicine，Indianapolis，Indiana 46202，USA；4复旦大学附属中山医院胃肠科，上海　200032；5上海交通大学医学院附属上海市精神卫生中心放射科，上海　200030）

摘要：研究目的：克罗恩病是一种慢性非特异性炎症性肠病，患者以腹痛、腹泻和体重减轻为主要特征。针灸治疗克罗恩病（CD）已经证实确有疗效，但其起效机制尚不明确。近来研究证实，脑-肠互动功能异常可能在CD的发生发展中占有重要地位。本研究旨在观察电针和艾灸疗法治疗缓解期CD患者脑神经响应特征的差异。研究方法：65名缓解期CD患者随机分为电针组（n=32）和艾灸组（n=33），两组均选取天枢（双）、气海和中脘穴。电针组采用0.30×40mm毫针刺入得气后接韩氏穴位神经刺激仪（HANS-100），疏密波刺激，频率2/100Hz，电流强度1-2mA，留针30min。艾灸组采用附子、黄连、木香、红花、丹参、当归加麦芽糖3g用温水调成厚糊状，用模具按压成直径23mm、厚5mm大小药饼，上置艾条高16mm，直径18mm艾柱进行隔药灸。每次每穴灸2壮。两组均隔日1次，每周3次。共治疗12周。电针组18人和艾灸组20人分别于治疗前和治疗12周后各完成了静息态脑功能磁共振（fMRI）扫描一次，采用基于种子点的全脑功能连接度分析方法对两组患者双侧海马的静息态功能连接度（rsFC）进行组内和组间比较。采用克罗恩病活动指数（CDAI）和炎症性肠病问卷（IBDQ）评分评估患者病情严重度和生活质量。Pearson相关性分析用来观察静息态功能连接度（rsFC）的改变与临床疗效变化量的相关性。研究结果：经过电针和艾灸治疗后，两组患者的CDAI评分均显著降低，IBDQ评分均显著增加。电针组双侧海马与中扣带回（MCC）和脑岛（insula）的rsFC显著增加，且与CDAI评分的改变量呈显著负相关；艾灸组患者双侧海马与楔前叶和下顶叶的rsFC显著增加且与CDAI评分的改变量呈显著负相关。研究结论：电针和艾灸疗法治疗缓解期CD患者具有不同的脑神经响应特征。以稳态传入网络为主的调节可能是电针疗法的脑响应特征；以默认模式网络（DMN）为主的调节可能是艾灸疗法的脑响应特征。　

关键词: 针刺；艾灸；克罗恩病；功能磁共振成像；功能连接

The Effect of Electro-acupuncture and Moxibustion on Brain Function in Patients with Crohn’s Disease: a Resting-state Functional Magnetic Resonance Imaging Study

Chunhui Bao¹，Di Wang¹, Peng Liu², Yin Shi¹, Xiaoming Jin³, Luyi Wu¹, Xiaoqing Zeng⁴, Jianye Zhang⁵, Huirong Liu^1#, Huangan Wu1#

(1 Shanghai Research Institute of Acupuncture and Meridian, Shanghai, 200030, China;2 Life Sciences Research Center, School of Life Sciences and Technology, Xidian University, Xi’an, Shaanxi, 710071, China;3 Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA;4 Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China;5 Department of Radiology, Shanghai Mental Health Center, Shanghai Jiaotong University School of Medicine, Shanghai, 200030, China)

Abstract: Background and Objective: Crohn's disease (CD) is a chronic inflammatory disease characterized by abdominal pain, diarrhea, and weight loss. Acupuncture and moxibustion have been shown to be effective in treating Crohn's disease (CD), but their precise therapeutic mechanisms of action remain unclear. Recent studies have confirmed that the abnormal brain - bowel interaction may play an important role in the development of CD. The purpose of this study was to observe the difference between electro-acupuncture and moxibustion in CD patients. Study Design/Materials and Methods: A total of 65 patients were randomly divided into an electro-acupuncture group (n=32) or a moxibustion group (n=33), and treated for 12 weeks. Four acupoints were selected in both groups, including ST25 (stomach, Tianshu, bilateral), CV6 (conception vessel, Qihai) and CV12 (Zhongwan; Figure 1). The electro-acupuncture group used 0.30 x 40mm needle. After achieving the Qi of acupuncture, needles were connected to a Han's Acupoint Nerve Stimulator (HANS-100). Dense disperse waves were generated (frequency 2/100 Hz, current intensity 1-2 mA), and the needles were left in place for 30 min. Moxibustion group was composed of Monkshood, Coptis chinensis, Radix aucklandiae, Carthamus tinctorius, Salvia, and Angelica sinensis mixed with maltose (3g) and made into a paste with warm water. The herbal cake was prepared to a uniform size using a mold (23 mm in diameter, 5 mm in thickness). For each herbal cake, two16mm high and 18mm diameter moxa-cones were performed. Two moxa-cones each time. Both groups was treated in once every two days with three times a week. Eighteen patients in the electro-acupuncture group and 20 patients in the moxibustion group underwent resting-state functional magnetic resonance imaging at baseline and after treatment. Seed-based analysis was used to compare the resting-state functional connectivity (rsFC) between the bilateral hippocampus and other brain regions before and after each treatment, as well as between the two groups. The CD activity index (CDAI) and inflammatory bowel disease questionnaire (IBDQ) were used to evaluate disease severity and patient quality of life. Pearson correlation analysis was used to observe the correlation between changes in the functional connectedness (rsFC) and the change in clinical efficacy. Results: Following treatment in both groups, the CDAI values were significantly reduced, while the IBDQ scores were significantly increased. In the electro-acupuncture group, the rsFC values were significantly increased between the bilateral hippocampus and the anterior middle cingulate cortex and the insula, the strengths of which were negatively correlated with the CDAI scores. In the moxibustion group, the rsFC values between the bilateral hippocampus and the precuneus as well as the inferior parietal lobe were significantly elevated, and negatively correlated with the CDAI scores. Conclusions: The therapeutic effects of electro-acupuncture and moxibustion might be due to the modulation of the homeostatic afferent processing network and the default mode network, respectively.

Keywords: acupuncture, moxibustion, Crohn’s disease, fMRI, functional connectivity