Clinical Trials Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 4986-4996
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4986
Moxibustion combined with acupuncture increases tight junction protein expression in Crohn’s disease patients
Hai-Xia Shang, An-Qi Wang, Chun-Hui Bao, Huan-Gan Wu, Wei-Feng Chen, Lu-Yi Wu, Rong Ji, Ji-Meng Zhao, Yin Shi
Hai-Xia Shang, An-Qi Wang, Lu-Yi Wu, Rong Ji, Ji-Meng Zhao, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Chun-Hui Bao, Huan-Gan Wu, Yin Shi, Shanghai Institute of Acupuncture-Moxibustion and Meridian, Shanghai 200030, China
Wei-Feng Chen, Zhongshan Hospital affiliated to Fudan University, Shanghai 200032, China
Author contributions: Shang HX, Wang AQ and Bao CH contributed equally to this work; Shi Y designed the study; Wang AQ, Bao CH and Wu LY contributed to the patient enrollment; Bao CH and Wu LY performed the moxibustion and acupuncture procedure; Chen WX performed enteroscopy and tissue sampling; Ji R and Shang HX performed the assays; Zhao JM analyzed the data; Wang AQ and Shang HX drafted the figures and wrote the manuscript; Wu HG and Shi Y conducted the study and revised the manuscript.
Supported by National Natural Science Foundation of China, No. 30772831, No. 81473757; and the National Basic Research Program of China, 973 Program, No. 2009CB522900.
Ethics approval: This study has been approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine approved the research project, No. 2009-02.
Clinical trial registration: This study is registered at the Chinese Clinical Trial Register Center. The registration identification number is ChiCTR-TRC-10000950.
Informed consent: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest: All authors stated that there is no conflict of interest related to the manuscript.
Data sharing: Technical appendix, statistical code, and dataset available from the corresponding author at flysy0636@163.com. Participants gave informed consent for data sharing.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yin Shi, MD, PhD, Shanghai Institute of Acupuncture-Moxibustion and Meridian, No. 650 South Wanping Road, Xuhui District, Shanghai 200030, China. flysy0636@163.com
Telephone: +86-21-64383910 Fax: +86-21-64644238
Received: November 13, 2014
Peer-review started: November 15, 2014
First decision: December 2, 2014
Revised: December 9, 2014
Accepted: February 5, 2015
Article in press: February 5, 2015
Published online: April 28, 2015
Abstract

AIM: To investigate the effect of herb-partitioned moxibustion combined with acupuncture on the expression of intestinal epithelial tight junction (TJ) proteins.

METHODS: Sixty patients diagnosed with mild to moderate Crohn’s disease (CD) were allocated into the herb-partitioned moxibustion combined with acupuncture (HMA) group (n = 30) or the mesalazine (MESA) group (n = 30) using a parallel control method. There were 2 sets of acupoints used alternately for HMA treatment. The following points were included in Set A: ST25 (Tianshu), RN6 (Qihai), and RN9 (Shuifen) for herb-partitioned moxibustion and ST36 (Zusanli), ST37 (Shangjuxu), LI11 (Quchi), and LI4 (Hegu) for acupuncture. The points for Set B included BL23 (Shenshu) and BL25 (Dachangshu) for herb-partitioned moxibustion and EX-B2 of T6-T1 (Jiajixue) for acupuncture. The patients received the same treatment 6 times a week for 12 consecutive weeks. The MESA group received 1 g of mesalazine enteric coated tablets 4 times daily for 12 consecutive weeks. Intestinal tissues were stained and examined to compare the morphological and ultrastructural changes before and after the treatment session. Immunohistochemistry and in situ hybridization assays were used to detect the expression of intestinal epithelial TJ proteins zonula occludens-1 (ZO-1), occludin, and claudin-1. The mRNA levels were also evaluated.

RESULTS: After the treatment, both herb-partitioned moxibustion combined with acupuncture and mesalazine improved intestinal morphology and ultrastructure of CD patients; the patients treated with HMA showed better improvement. HMA significantly increased the expression of ZO-1 (P = 0.000), occludin (P = 0.021), and claudin-1 (P = 0.016). MESA significantly increased the expression of ZO-1 (P = 0.016) and occludin (P = 0.026). However, there was no significant increase in the expression of claudin-1 (P = 0.935). There was no statistically significant difference between the two groups for the expression of occludin and claudin-1 (P > 0.05). The HMA group showed a significant improvement in ZO-1 expression compared to the MESA group (2333.34 ± 352.51 vs 2160.38 ± 307.08, P = 0.047). HMA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.017), and claudin-1 mRNA (P = 0.017). MESA significantly increased the expression of ZO-1 mRNA (P = 0.000), occludin mRNA (P = 0.042), and claudin-1 mRNA (P = 0.041). There was no statistically significant difference between the two groups in the expression of occludin and claudin-1 mRNA (P > 0.05). However, the HMA group showed a significant improvement in ZO-1 mRNA expression compared with the MESA group (2378.17 ± 308.77 vs 2200.56 ± 281.88, P = 0.023).

CONCLUSION: HMA can repair intestinal epithelial barrier lesions and relieve inflammation by upregulating the expression of TJ proteins and their mRNAs.

Keywords: Crohn’s disease, Herb-partitioned moxibustion, Acupuncture, Intestinal epithelial cells, Tight junction proteins

Core tip: Crohn’s disease (CD) is a chronic relapsing inflammatory condition involving all layers of the gastrointestinal tract. Although its etiopathogenesis remains unclear, increased permeability of the intestinal epithelial barrier is one of the crucial factors in CD onset. Tight junctions (TJs) within intestinal epithelial cells form the structural basis of the intestinal epithelial barrier, and reduced expression of TJ proteins is positively correlated with CD severity. This study investigated the therapeutic effect of herb-partitioned moxibustion combined with acupuncture on CD. We found that this treatment upregulated the expression of intestinal epithelial TJ proteins and their mRNAs.