隔药饼灸对克罗恩病大鼠模型自噬及免疫相关基因表达谱的影响
Effect of Herb-Partitioned Moxibustion on Autophagy and Immune-Associated Gene Expression Profiles in a Rat Model of Crohn's Disease.
作者信息
Zhao Ji-Meng, Liu Ya-Nan, Zheng Han-Dan, Huang Yan, Qi Qin, Liu Hui-Rong, Shi Yin, Ma Xiao-Peng, Lu Yuan, Wu Lu-Yi
机构信息
Key Laboratory of Acupuncture and Immunological Effects, Shanghai Research Institute of Acupuncture and Meridian, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China.
Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
出版信息
Evid Based Complement Alternat Med. 2019 Mar 7;2019:3405146. doi: 10.1155/2019/3405146. eCollection 2019.
OBJECTIVE
To investigate the immune regulation mechanism of herb-partitioned moxibustion in rats with Crohn's disease (CD) focusing on autophagy.
METHODS
Rats were randomly divided into normal (N) group, CD model (M) group, CD model with herb-partitioned moxibustion (MM) group, normal with herb-partitioned moxibustion (NM) group, CD model with mesalazine (western medicine, Med ) group, and normal saline (NS) group, with 10 rats in each group. The CD model rats were prepared by trinitrobenzene sulphonic expect for the N group and NM group. After the CD rats model were established, the rats in the MM and NM groups were treated with herb-partitioned moxibustion at Tianshu (ST25) and Qihai (CV6) acupoints once daily for 7 days, and rats in the Med and NS groups were respectively treated with mesalazine enteric coated tablet and normal saline once daily for 7 days. After intervention, hematoxylin-eosin staining was used to observe the histological changes of colon; RNA sequencing was used to observe the changes in autophagy- and immune-associated gene expression profiles. In addition, autophagy- and immune-associated cytokines and signaling pathways in CD rats were also screened.
RESULTS
HPM significantly increased the body weight of CD rats (<0.01) and improved the pathological injury of colon in CD rats (<0.01). HPM also changed the expression of many autophagy- and immune-associated genes, especially downregulating the expression of autophagy-associated , genes as well as the receptor of immune-associated , (, ) genes in the colon of CD rats. HPM also changed the enrichment levels of differentially expressed genes in the human T-cell leukemia virus type-1 infection pathway, the Epstein-Barr virus infection pathway, and the cell adhesion molecule pathway. In addition, the expression levels of Nod2, Irgm, IL-12b, and IL-22 mRNA were increased (all < 0.01) in the M group compared to the N group, while the expression levels of Nod2, Irgm, IL-12b, and IL-22 mRNA were decreased (<0.05 or <0.01) in the MM and Med groups compared to the M group.
CONCLUSION
Herb-partitioned moxibustion may effectively attenuate intestinal inflammation and promote the repair of colon mucosal injury of CD rats through the regulation of autophagy- and immune-associated gene expression and signaling pathways.
目的
以自噬为重点，探讨隔药灸对克罗恩病（CD）大鼠的免疫调节机制。
方法
将大鼠随机分为正常（N）组、CD模型（M）组、隔药灸治疗CD模型（MM）组、正常大鼠隔药灸（NM）组、美沙拉嗪（西药，Med）治疗CD模型组和生理盐水（NS）组，每组10只。除N组和NM组外，其余大鼠采用三硝基苯磺酸制备CD模型。CD大鼠模型建立后，MM组和NM组大鼠于天枢（ST25）和脐海（CV6）穴位每日进行1次隔药灸，共7天；Med组和NS组大鼠分别每日给予美沙拉嗪肠溶片和生理盐水，共7天。干预后，采用苏木精-伊红染色观察结肠组织学变化；采用RNA测序观察自噬和免疫相关基因表达谱的变化。此外，还筛选了CD大鼠自噬和免疫相关细胞因子及信号通路。
结果
隔药灸显著增加了CD大鼠的体重（<0.01），改善了CD大鼠结肠的病理损伤（<0.01）。隔药灸还改变了许多自噬和免疫相关基因的表达，特别是下调了CD大鼠结肠中自噬相关基因、基因以及免疫相关基因、（、）受体的表达。隔药灸还改变了人类T细胞白血病病毒1型感染途径、爱泼斯坦-巴尔病毒感染途径和细胞黏附分子途径中差异表达基因的富集水平。此外，与N组相比，M组中Nod2、Irgm、IL-12b和IL-22 mRNA的表达水平升高（均<0.01），而与M组相比，MM组和Med组中Nod2、Irgm、IL-12b和IL-22 mRNA的表达水平降低（<0.05或<0.01）。
结论
隔药灸可能通过调节自噬和免疫相关基因表达及信号通路，有效减轻肠道炎症，促进CD大鼠结肠黏膜损伤的修复。
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