Applying Complex Network and Cell-Cell Communication Network Diagram Methods to Explore the Key Cytokines and Immune Cells in Local Acupoint Involved in Acupuncture Treating Inflammatory Pain

Kuo Zhang; Xue Zhao; Shasha Ding; Yangyang Liu; Yuan Xu; Yawen Yan; Shouhai Hong; Fuming Yang; Shenjun Wang; Zhifang Xu; Yongming Guo; Yi Guo; Guangchang Pang; Jiang Wang; Xinmeng Guo; Miao Zhao

doi:10.1155/2020/2585960

Applying Complex Network and Cell-Cell Communication Network Diagram Methods to Explore the Key Cytokines and Immune Cells in Local Acupoint Involved in Acupuncture Treating Inflammatory Pain

Evid Based Complement Alternat Med. 2020 Jul 29:2020:2585960. doi: 10.1155/2020/2585960. eCollection 2020.

Authors

Kuo Zhang^{1

2}, Xue Zhao², Shasha Ding³, Yangyang Liu², Yuan Xu², Yawen Yan², Shouhai Hong⁴, Fuming Yang⁵, Shenjun Wang², Zhifang Xu², Yongming Guo², Yi Guo⁶, Guangchang Pang⁷, Jiang Wang⁸, Xinmeng Guo⁸, Miao Zhao⁷

Affiliations

¹ Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China.
² Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
³ Department of Acupuncture and Physical Therapy, Tianjin Nankai Hospital, Tianjin 300100, China.
⁴ Acupuncture Department, Zhejiang Provincial Hospital of TCM, Hangzhou, Zhejiang 310006, China.
⁵ Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, Jiangsu 210093, China.
⁶ School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
⁷ Tianjin Key Laboratory of Food Biotechnology, Faculty of Biotechnology and Food Science, Tianjin University of Commerce, Tianjin 300134, China.
⁸ School of Electrical Engineering and Automation, Tianjin University, Tianjin 300072, China.

Abstract

Manual acupuncture (MA) can effectively treat a variety of diseases, but its specific mechanism remains unclear. The "acupoint network" activated by MA participates in MA signal transduction, in which immune-related cells and cytokines play an important role. However, which cells and cytokines in the acupoint have changed after MA? What is the network relationship between them? Which cells and cytokines may play the most important role in MA effect? These problems are unclear. In this study, on the basis of affirming the analgesic, detumescence, and anti-inflammatory effect of MA, the concentration of 24 cytokines in ST36 acupoint in rats with inflammatory pain after MA treatment was detected by multiplex immunoassay technology. Then, using statistical and complex network and cell-cell communication (CCC) network diagram method to analyze the detected data depicts the network relationship between the cytokines and related cells objectively and establishes cytokine connection network and CCC network, respectively. The results showed that MA reinforced communication intensity between cells while reducing the overall correlation intensity. On this basis, the key cytokines and key cells at three MA time-points were screened out, cytokines IL-6, MCP-1, fibroblasts cell, and monocyte macrophage screened by the three methods at three MA time-points might be the key cytokines or key cells. After that, we detected the macrophages in ST36 acupoint by flow cytometry and immunofluorescence and found that the relative amount of macrophages increased significantly after MA, especially the macrophage of the dermis of skin. This study provided a basis for revealing the initiated mechanism of MA effect.