Effect of Sishen Pill on Memory T Cells From Experimental Colitis Induced by Dextran Sulfate Sodium
Effect of Sishen Pill on Memory T Cells From Experimental Colitis Induced by Dextran Sulfate Sodium
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四神丸对右旋糖酐硫酸钠诱导的实验性结肠炎记忆T细胞的影响
DOI：
10.3389/fphar.2020.00908
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发表时间：
2020-07-02
影响因子：
5.6
通讯作者：
Liu, Duan-Yong
中科院分区：
文献类型：
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作者：
Ge, Wei;Wang, Hai-Yan;Liu, Duan-Yong
免疫记忆对人体具有保护作用，但异常的免疫记忆与包括炎症性肠病（IBD）在内的自身免疫性疾病的发生、发展密切相关。四神丸是中医经典方剂，常用于治疗慢性结肠炎，但四神丸是否通过重塑免疫记忆来缓解实验性结肠炎尚不清楚。本研究通过结肠长度、结肠重量指数、大体和显微评分以及病理学观察，评价SSP对葡聚糖硫酸钠（DSS）诱导的慢性结肠炎的治疗作用。采用酶联免疫吸附试验（ELISA）检测细胞因子水平，流式细胞术检测中枢记忆T细胞（Tcm）和效应记忆T细胞（Tem）百分比，Western印迹法检测磷酸肌醇3-激酶（PI 3 K）/Akt信号蛋白的活化。治疗7 d后，SSP可减轻DSS诱导的结肠炎，表现为结肠重量指数、结肠重量、组织病理学损伤评分降低，结肠长度恢复，结肠黏膜逐渐恢复，IL-2、IL-7、IL-12和IL-15水平降低，而SSP可增加IL-10的表达。SSP对Tcm和Tem细胞的数量和亚群有明显的调节作用。此外，SSP显著抑制PI 3 K/Akt信号通路中PI 3 K、Akt、磷酸化Akt、Id 2、T-bet、叉头盒O3 a、Noxa和C-myc蛋白的激活，并激活Rictor、Raptor、结节性硬化症复合体（TSC）1、TSC 2、磷酸化AMP激活激酶（AMPK）-α、AMPK-α、真核翻译起始因子4 E结合蛋白2、驱动蛋白家族成员2a、和70-kDa核糖体蛋白S6激酶。结果表明，SSP能有效抑制外周血Tem细胞，减轻DSS诱导的实验性结肠炎，其机制可能与抑制PI 3 K/Akt信号通路有关。
Immune memory has a protective effect on the human body, but abnormal immune memory is closely related to the occurrence and development of autoimmune diseases including inflammatory bowel disease (IBD). Sishen Pill (SSP) is a classic prescription of traditional Chinese medicine, which is often used to treat chronic colitis, but it is not clear whether SSP can alleviate experimental colitis by remodeling immune memory. In the present study, the therapeutic effect of SSP on chronic colitis induced by dextran sulfate sodium (DSS) was evaluated by colonic length, colonic weight index, macroscopic and microscopic scores, and pathological observation. The cytokine levels were tested by enzyme-linked immunosorbent assay (ELISA); the percentages of central memory T (Tcm) and effector memory T (Tem) cells were analyze\d by flow cytometry; and activation of phosphoinositide 3-kinase (PI3K)/Akt signaling proteins was measured by western blotting. After 7-days' treatment, SSP alleviated DSS-induced colitis, which was demonstrated by decreased colonic weight index, colonic weight, histopathological injury scores, restored colonic length, gradual recovery of colonic mucosa, and lower levels of interleukin (IL)-2, IL-7, IL-12, and IL-15, while SSP increased IL-10 expression. SSP obviously regulated the quantity and subpopulation of Tcm and Tem cells. Furthermore, SSP markedly inhibited activation of PI3K, Akt, phospho-Akt, Id2, T-bet, forkhead box O3a, Noxa, and C-myc proteins in the PI3K/Akt signaling pathway and activated Rictor, Raptor, tuberous sclerosis complex (TSC)1, TSC2, phospho-AMP-activated kinase (AMPK)-α, AMPK-α, eukaryotic translation initiation factor 4E-binding protein 2, kinesin family member 2a, and 70-kDa ribosomal protein S6 kinase. These results indicate that SSP effectively controls Tem cells in the peripheral blood to relieve experimental colitis induced by DSS, which were potentially related with inhibiting the PI3K/Akt signaling pathway.