丁酸增加酒精性肝病小鼠单核细胞性髓源性抑制细胞数量及抑炎因子水平  

Butyrate increases the monocytic myeloid-derived suppressor cells and promotes the secretion of anti-inflammatory cytokines in mice with alcoholic liver disease

作　　者：任艺 张晓霞 何芳[2] 鲍婷 汪婷 李一唯 汪蕊 王浩[4] 杨少奇[2] REN Yi;ZHANG Xiaoxia;HE Fang;BAO Ting;WANG Ting;LI Yiwei;WANG Rui;WANG Hao;YANG Shaoqi(Clinical Medical College,Department of Gastroenterology,General Hospital,Ningxia Medical University,Yinchuan 750004,China;College of Chinese Traditional Medicine,Ningxia Medical University,Yinchuan 750004,China;Department of Pathogenic Biology and Medical University,Ningxia Medical University,Yinchuan 750004,China;School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏医科大学临床医学院,宁夏银川750004 [2]宁夏医科大学总医院消化内科,宁夏银川750004 [3]宁夏医科大学中医学院中医基础系,宁夏银川750004 [4]宁夏医科大学病原生物学与医学免疫学系,宁夏银川750004

出　　处：《细胞与分子免疫学杂志》2022年第10期865-871,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81602713,82160122);宁夏“十三五”重大科技项目(2016BZ02)。

摘　　要：目的探讨丁酸对酒精性肝病(ALD)小鼠单核细胞性髓源性抑制细胞(M-MDSC)以及血浆炎症因子的影响。方法将60只雌性C57BL/6J小鼠随机分为阴性对照组、ALD模型组、丁酸钠(NaB)干预对照组、NaB干预模型组。对照组给予Lieber-DeCarli对照液体饮食,模型组给予等热量Lieber-DeCarli酒精液体饮食,同时NaB干预组给予含NaB(0.6 g/kg)的液体饮食喂养。喂养6周后,采用流式细胞术检测小鼠外周血、肝脏和脾脏细胞中M-MDSC比例;细胞因子流式微球阵列(CBA)技术检测血浆中肿瘤坏死因子α(TNF-α)、白细胞介素10(IL-10)的表达水平,并分析M-MDSC比例与血浆炎症因子的相关性。结果与阴性对照组相比,ALD模型组外周血、肝脏和脾脏细胞中M-MDSC比例显著增加,血浆中TNF-α水平升高,IL-10水平降低。与ALD模型组相比,NaB模型组外周血、肝脏和脾脏细胞中M-MDSC比例明显增加。NaB干预后血浆TNF-α水平降低,IL-10水平升高。外周血、肝脏和脾脏中M-MDSC分别与TNF-α呈负相关,与IL-10呈正相关。结论NaB通过招募外周血、肝脏、脾脏细胞中M-MDSC和抑制小鼠炎症反应进而缓解ALD的进展。Objective To investigate the effect of butyrate on monocytic myeloid-derived suppressor cells(M-MDSCs)and plasma inflammatory cytokines in mice with alcoholic liver disease(ALD).Methods Sixty female C57BL/6J mice were randomly divided into 4 groups:negative control group,ALD model group,sodium butyrate(NaB)-treated control group and NaB-treated ALD model group.The control groups were fed with ethanol-free modified Lieber-DeCarli liquid diets,while the model groups were fed with ethanol-containing modified Lieber-DeCarli liquid diets.Meanwhile,mice in the NaB-treated groups were given a liquid diet containing NaB(0.6 g/kg).After 6 weeks of feeding,the proportions of M-MDSCs in the peripheral blood,liver and spleen cells were detected by flow cytometry.Concentrations of plasma inflammatory cytokines including tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)were determined by cytometric bead array(CBA).The correlation between the proportion of M-MDSCs and plasma inflammatory cytokines were analyzed.Results Compared with negative control group,the proportions of M-MDSCs of the peripheral blood,liver and spleen cells in ALD model group increased significantly;plasma TNF-α level also dramatically increased;plasma IL-10 concentration,however,decreased considerably.In contrast,compared to ALD model group,the proportions of M-MDSCs of the peripheral blood,liver and spleen cells in NaB-treated ALD model group significantly increased.The level of plasma TNF-α decreased and plasam IL-10 concentration increased after NaB treatment.Moreover,the proportions of M-MDSCs in peripheral blood,liver and spleen were negatively correlated with TNF-α and positively correlated with IL-10.Conclusion NaB may alleviate the progression of ALD by involving M-MDSCs in the peripheral blood,liver,spleen and suppressing inflammation in mice.

关 键 词：酒精性肝病(ALD) 丁酸 单核细胞性髓源性抑制细胞(M-MDSC) 炎症因子 

分 类 号：R575.1[医药卫生—消化系统] R392.3[医药卫生—内科学] R364.5[医药卫生—临床医学] R333.6