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Archive > Volume 17 Issue 2 > 2025,17(2):380-391. DOI:https://doi.org/10.1016/j.chmed.2024.02.004 Prev Next

半夏瀉心湯通過調(diào)節(jié)STAT3信號傳導(dǎo)和腸道微生物群抑制結(jié)腸炎相關(guān)性結(jié)直腸癌的發(fā)展

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Banxia Xiexin Decoction inhibits colitis-associated colorectal cancer development by modulating STAT3 signaling and gut microbiota

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    摘要:
    目的：基于炎癥和腸道菌群平衡闡明半夏瀉心湯改善氧偶氮甲烷(AOM)/葡聚糖硫酸鈉(DSS)誘導(dǎo)的結(jié)直腸癌小鼠的作用機制。方法：將 75只C57BL/6隨機分為正常對照組（NC）、模型組（Model）、半夏瀉心湯低劑量組（L-BXD）、半夏瀉心湯高劑量（H-BXD）和美沙拉嗪組（MS）.BXD（3.915 g/kg和15.66 g/kg）和美沙拉秦（0.6 g/kg）治療周期為3周。使用蘇木精-伊紅（HE）染色觀察結(jié)腸的組織病理學(xué)變化。通過酶聯(lián)免疫吸附試驗（ELISA）檢測血清中炎癥因子的含量，并評估免疫、細(xì)胞凋亡、炎癥和炎癥因子相關(guān)基因的mRNA和蛋白表達(dá)?；?6S rRNA高通量測序測定小鼠糞便中腸道菌群的變化。結(jié)果：與模型組相比，低、高劑量BXD減少小鼠的結(jié)腸腫瘤數(shù)量，逆轉(zhuǎn)體重減輕趨勢，縮短結(jié)腸長度。病理染色顯示BXD減輕結(jié)腸腫瘤的惡性程度。抑制信號轉(zhuǎn)導(dǎo)子和轉(zhuǎn)錄激活子3（STAT3）、基質(zhì)金屬蛋白酶-9（MMP-9）和轉(zhuǎn)化生長因子β1（TGF-β1）的表達(dá)，同時增加結(jié)腸組織中緊密連接蛋白ZO-1的表達(dá)。此外，參與炎癥的關(guān)鍵通路蛋白（磷酸化的STAT3、Bcl-2、COX-2）和細(xì)胞周期調(diào)節(jié)分子（c-Myc和PCNA）的水平降低。結(jié)合16S rRNA序列分析，BXD提高潛在有益細(xì)菌的相對豐度，降低癌癥相關(guān)細(xì)菌的相對富集度。結(jié)論：BXD對結(jié)直腸癌的發(fā)生具有一定的預(yù)防作用；其機制與抑制炎癥和腫瘤增殖以及維持腸道穩(wěn)態(tài)有關(guān)。

    Abstract:
    Objective: To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS). Methods: A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high throughput sequencing of the 16S rRNA microbial gene. Results: Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-b1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased. Conclusion: BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.

    關(guān)鍵詞:
    半夏瀉心湯;結(jié)直腸腫瘤;腸道菌群;炎癥;信號轉(zhuǎn)導(dǎo)因子和轉(zhuǎn)錄激活因子3（STAT3）

    Keywords:


    Project Supported:
    This work was supported by the Natural Science Foundation of Nanjing University of Chinese Medicine (No. XZR2020038); Science and Technology Innovation Project of Suzhou Medical and Health Care (No. SKJY2021136, SKY2023216) and Fifth Batch of Gusu Health Personnel Training Project in Suzhou (No. GSWS2020085).

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