隔物灸通过上调克罗恩病模型小鼠 A20 的表达改善肠道上皮细胞紧密连接。
Herbs-partitioned moxibustion improves intestinal epithelial tight junctions by upregulating A20 expression in a mouse model of Crohn's disease.
机构信息
Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Outpatient Department, Shanghai Research Institute of Acupuncture and Meridian, Shanghai, 200030, China.
Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
出版信息
Biomed Pharmacother. 2019 Oct;118:109149. doi: 10.1016/j.biopha.2019.109149. Epub 2019 Jul 12.
BACKGROUND
To investigate effects moxibustion exerts on A20 expression and regulation of intestinal epithelial tight junctions via the TNF-α-NF-κB-MLCK pathway in Crohn's disease (CD).
METHODS
C57BL/6 wild type (WT) and A20 mice (48 each) were randomly divided into normal control (NC), model control (MC), mesalazine (MESA) and herbs-partitioned moxibustion (HPM) groups (12 mice per group). An experimental model of CD was established using 2, 4, 6 trinitrobenzene sulfonic acid. MESA and HPM mice were treated with MESA and HPM (at Tianshu (ST25) and Qihai (CV6)), respectively. In HPM group, moxa cones (0.5 cm in diameter and 0.3 cm in height) made of refined mugwort floss were placed on herbal cakes (medicinal formula dispensing [radix] Aconiti praeparata, [cortex] Cinnamomi, etc.) at Tianshu (ST25) and Qihai (CV6) and ignited. The moxa cones were ignited, and two moxa cones were used for each treatment once daily for 10 days. In MESA group, mice were fed MESA, which was prepared at a proportion of 1:0.0026, twice daily for 10 days.
RESULTS
Intestinal epithelial ultrastructure of WT HPM mice improved more than A20 HPM mice compared to MC mice. WT HPM mice exhibited greater expression of A20 compared with MC mice (P < 0.01). TNF-α, NF-kB p65, MLCK, MLC, TRAF6 and RIP1 levels in A20 and WT HPM mice were all decreased compared to MC mice (P < 0.01). NF-κB p65、MLCK and TRAF6 levels were increased in A20 HPM mice as compared to WT HPM mice (P < 0.05). Intestinal epithelial levels of occludin, claudin-1, ZO-1 and F-actin increased in all HPM mice (P < 0.01-0.05), while occludin, claudin-1, and ZO-1 levels were lower in A20 HPM mice (P < 0.05, P < 0.01, P < 0.01).
CONCLUSION
HPM downregulates abnormal activation of the TNF-α-NF-κB-MLCK pathway by upregulating expression of A20 in a mouse model of CD, thereby protecting intestinal epithelial tight junctions and repairing the damage CD causes to the intestinal epithelial barrier.
背景
研究艾灸通过 TNF-α-NF-κB-MLCK 通路对克罗恩病（CD）中 A20 表达和肠上皮紧密连接的调节作用。
方法
将 48 只 C57BL/6 野生型（WT）和 A20 小鼠随机分为正常对照组（NC）、模型对照组（MC）、美沙拉嗪（MESA）和艾灸组（HPM）（每组 12 只）。采用 2,4,6-三硝基苯磺酸建立 CD 实验模型。MESA 和 HPM 组分别给予 MESA 和 HPM（ST25 和 CV6）治疗。在 HPM 组中，将直径 0.5cm、高 0.3cm 的精制艾绒制成艾炷置于天枢（ST25）和气海（CV6）的药饼上（处方配药[制]乌头、[肉桂]桂皮等）并点燃。艾炷点燃后，每天治疗一次，每次 2 个艾炷。在 MESA 组中，每天两次给予 MESA，比例为 1:0.0026，连续 10 天。
结果
与 MC 组相比，WT HPM 组小鼠肠上皮超微结构改善优于 A20 HPM 组。与 MC 组相比，WT HPM 组小鼠 A20 的表达更高（P<0.01）。与 MC 组相比，A20 和 WT HPM 组小鼠的 TNF-α、NF-κB p65、MLCK、MLC、TRAF6 和 RIP1 水平均降低（P<0.01）。与 WT HPM 组相比，A20 HPM 组小鼠的 NF-κB p65、MLCK 和 TRAF6 水平升高（P<0.05）。所有 HPM 组小鼠的肠上皮 occludin、claudin-1、ZO-1 和 F-actin 水平均升高（P<0.01-0.05），而 A20 HPM 组小鼠的 occludin、claudin-1 和 ZO-1 水平较低（P<0.05，P<0.01，P<0.01）。
结论
HPM 通过上调 CD 模型中小鼠 TNF-α-NF-κB-MLCK 通路异常激活的 A20 表达，下调该通路，从而保护肠上皮紧密连接，修复 CD 对肠上皮屏障的损伤。
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