Abstract：Objective: To investigate the regulatory mechanism of mesalazine (MSLZ) on Let-7i-5p and TLR4/MyD88 signaling pathway in a mouse model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced ulcerative colitis (UC). Methods: A UC model was established using the TNBS/ethanol method. Forty-four male mice were randomly divided into four groups: control group, model group, MSLZ group, and Let-7i-5p inhibitor group, with 11 mice in each group. Mice were gavaged or intraperitoneally injected with corresponding drugs or saline for 14 consecutive days. The expression levels of Let-7i-5p in colon tissues and serum of mice were detected by real-time quantitative polymerase chain reaction (qRT-PCR). The pathological changes of colon tissues were observed by hematoxylin and eosin (HE) staining under a microscope. The mRNA and protein levels of TLR4/MyD88 signaling pathway-related genes in colon tissues of mice were detected by qRT-PCR, Western blot, and immunohistochemistry, respectively. The expression levels of TNF-α and IL-1β in mouse serum were detected by ELISA. Results: According to the disease activity index (DAI), colon damage score, and pathological lesion score, the mouse UC model was successfully established. The expression levels of Let-7i-5p in colon tissues and serum of mice in the model group were significantly higher than those in the control group (P<0.0001). Compared with the model group, both MSLZ and Let-7i-5p inhibitor treatment could significantly inhibit the expression of Let-7i-5p (P<0.0001). Compared with the control group, the mRNA and protein levels of TLR4/MyD88 signaling pathway-related genes (including TLR4, MyD88, TRAF-6, and NF-κB) in colon tissues of mice in the model group were significantly upregulated. MSLZ and Let-7i-5p inhibitor treatment could significantly inhibit the expression of these genes, and the inhibitory effect of MSLZ was slightly stronger than that of Let-7i-5p inhibitor. Compared with the control group, the mRNA levels of IL-1β and TNF-α in colon tissues and the protein levels in serum of mice in the model group were significantly upregulated. MSLZ and Let-7i-5p inhibitor treatment could inhibit the expression levels of IL-1β and TNF-α. Conclusion: In the TNBS/ethanol-induced UC mouse model, MSLZ can inhibit the expression of Let-7i-5p in colon tissues and serum. In addition, MSLZ can also inhibit the release of inflammatory factors by inhibiting the TLR4/MyD88-dependent pathway in UC mice.
毛珍珍, 刘靖, 张晨华, 闫娜娜, 赵玲玲, 卢军仪, 许伟光, 王婧. 美沙拉嗪对小鼠溃疡性结肠炎模型中Let-7i-5p/TLR4/MyD88依赖性通路的调控机制[J]. 河北医学, 2024, 30(4): 549-555.
MAO Zhenzhen, LIU Jing, ZHANG Chenhua, et al. Regulatory Mechanism of Mesalazine on Let-7i-5p/TLR4/MyD88 Signaling Pathway in a Mouse Model of Ulcerative Colitis. HeBei Med, 2024, 30(4): 549-555.
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2024, Vol. 30 
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