参苓控瘤方对小鼠结直肠腺瘤及TLR4/MyD88/NF-κB通路、巨噬细胞极化的影响-中国药房

参苓控瘤方对小鼠结直肠腺瘤及TLR4/MyD88/NF-κB通路、巨噬细胞极化的影响

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篇名：	参苓控瘤方对小鼠结直肠腺瘤及TLR4/MyD88/NF-κB通路、巨噬细胞极化的影响
TITLE：	Effects of Shenling kongliu formula on colorectal adenoma in mice and on the TLR4/MyD88/NF-κB pathway and macrophage polarization
摘要：	目的观察参苓控瘤方对结直肠腺瘤（CRA）小鼠的改善作用，以及对Toll样受体4（TLR4）/髓系分化初级反应蛋白88（MyD88）/核因子κB（NF-κB）信号通路和巨噬细胞极化的影响。方法将30只雄性ApcMin/+小鼠随机分为模型组、阿司匹林组[阳性对照，20.59mg/（kg·d）]和参苓控瘤方低、中、高剂量组[2.06、4.11、8.22g/（kg·d）]，每组6只；另取6只野生型雄性C57BL/6J小鼠，作为野生对照组。各组小鼠每天灌胃相应药液或生理盐水2次，连续12周。末次给药后，检测各组小鼠血清中白细胞介素10（IL-10）、肿瘤坏死因子α（TNF-α）水平，统计其全段结直肠中的腺瘤总数及平均最长径，观察其结直肠组织病理学改变，检测其结直肠组织中分化簇86（CD86）、CD206、诱导型一氧化氮合酶（iNOS）、精氨酸酶1（ARG-1）、TLR4、MyD88、NF-κBp65蛋白的表达情况。结果与模型组相比，参苓控瘤方各剂量组小鼠结直肠组织腺瘤样病变、炎症细胞浸润等病理改变均有不同程度改善；其血清中IL-10、TNF-α水平，腺瘤总数及平均最长径（低剂量组除外），CD86阳性表达、CD206阳性表达（低剂量组除外），以及iNOS、TLR4、MyD88、NF-κBp65蛋白的表达均显著降低、减少、缩短或下调，而ARG-1蛋白的表达（低剂量组除外）均显著上调（P＜0.05）。Jonckheere-Terpstra检验显示，随着参苓控瘤方剂量的增加，小鼠IL-10、TNF-α水平，腺瘤总数及平均最长径，CD86和CD206阳性表达及MyD88蛋白表达均呈递减趋势，而ARG-1蛋白表达则呈递增趋势（P＜0.05）。结论参苓控瘤方可减轻ApcMin/+小鼠CRA负荷并改善腺瘤组织病理改变，其干预效应伴随TLR4/MyD88/NF-κB通路相关蛋白、炎症因子及巨噬细胞极化相关标志物的表达变化。
ABSTRACT：	OBJECTIVE To investigate the improvement effects of the Shenling kongliu formula （SLKLF） on mice with colorectal adenoma （CRA）， as well as its impact on the Toll-like receptor 4 （TLR4）/myeloid differentiation primary response protein 88 （MyD88）/nuclear factor-κB （NF-κB） pathway and on the macrophage polarization.METHODS Thirty male Apc Min/+ mice were randomly divided into a model group， an aspirin group [positive control， 20.59 mg/（kg·d）]， and low-， medium- and high-dose SLKLF groups [2.06， 4.11 and 8.22 g/（kg·d）]， with six mice in each group. Additionally， 6 wild-type male C57BL/6J mice were used as the wild-type control group. Mice in each group were gavaged twice daily with the corresponding drug solution or normal saline for 12 consecutive weeks. After the final administration， the levels of interleukin-10 （IL-10） and tumor necrosis factor-α （TNF-α） in the serum of mice in each group were measured， the total number of adenomas and the average longest diameter in the entire colon and rectum were counted， histopathological changes in colorectal tissues were observed， and the protein expressions of cluster of differentiation 86 （CD86）， CD206， inducible nitric oxide synthase （iNOS）， arginase-1 （ARG-1）， TLR4， MyD88， and NF-κB p65 in the colorectal tissue were detected.RESULTS Compared with the model group， mice in all SLKLF dose groups showed varying degrees of improvement in pathological changes such as colorectal adenomatous lesions and inflammatory cell infiltration. Their serum levels of IL-10 and TNF-α， total number of adenomas and their average longest diameter （except in the low-dose group）， CD86-positive and CD206-positive （except in the low-dose group） expressions， as well as the protein expressions of iNOS， TLR4， MyD88， NF-κB p65 were all significantly reduced， decreased， shortened， or downregulated， while the protein expression of ARG-1 （except in the low-dose group） was significantly upregulated （ P ＜0.05）. The Jonckheere-Terpstra tests showed that， as the SLKLF dose increased， the levels of IL-10 and TNF-α， the total number of adenomas， the average longest diameter， CD86-positive and CD206-positive expressions， and the protein expression of MyD88 in mice all showed a decreasing trend， while the protein expression of ARG-1 showed an increasing trend （ P ＜0.05）.CONCLUSIONS SLKLF can reduce the CRA burden in Apc Min/+ mice and improve histopathological changes in the adenomas. Its therapeutic effects are accompanied by changes in the expression of proteins associated with the TLR4/MyD88/NF-κB pathway， inflammatory factors， and markers related to macrophage polarization.
期刊：	2026年第37卷第20期
作者：	王锦程；吴培；代博；王子涵；周素芳
AUTHORS：	WANG Jincheng，WU Pei，DAI Bo，WANG Zihan，ZHOU Sufang
关键字：	参苓控瘤方;结直肠腺瘤;巨噬细胞极化;TLR4/MyD88/NF-κB通路
KEYWORDS：	Shenling kongliu formula;colorectal adenoma;Macrophage polarization;TLR4/MyD88/NF-κB pathway
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