桦木酸对右旋糖酐硫酸钠诱导的小鼠结肠炎的保护作用  

Protective Effect of Betulinic Acid against Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

作　　者：杨茗淇 黄优 孔丽 何家宇 伍娇 杨宇[1] 姚欢 朱利娟[1,2] 易金娥 YANG Mingqi;HUANG You;KONG Li;HE Jiayu;WU Jiao;YANG Yu;YAO Huan;ZHU Lijuan;YI Jin’e(Hunan Engineering Research Center of Livestock and Poultry Health Care,College of Veterinary Medicine,HunanAgricultural University,Changsha 410128,China;School of Public Health,University of South China,Hengyang 421001,China)

机构地区：[1]湖南农业大学动物医学院,畜禽保健湖南省工程研究中心,湖南长沙410128 [2]南华大学公共卫生学院,湖南衡阳421001

出　　处：《食品科学》2024年第17期88-95,共8页Food Science

基　　金：国家自然科学基金面上项目(32273084);湖南省研究生科研创新基金项目(CX20220670);湖南农业大学研究生科研创新基金项目(2022XC010)。

摘　　要：目的:研究桦木酸(betulinic acid,BA)对右旋糖酐硫酸钠(dextran sodium sulfate,DSS)诱导结肠炎的影响。方法:将84只C57BL/6小鼠随机分为7组,即对照组,BA组(0.5 mg/kg),DSS组(质量分数4%),BA低、中、高剂量(0.25、0.5、1 mg/kg)+DSS组,5-氨基水杨酸(5-aminosalicylic acid,5-ASA)(50 mg/kg)+DSS组。BA或5-ASA连续灌胃14 d,从第8天开始每天饮用4%DSS水溶液,连续7 d诱导小鼠结肠炎,随后测量小鼠结肠长度,苏木精&伊红染色和透射电镜观察结肠病理变化与超微结构,免疫荧光染色法检测活性氧(reactive oxygen species,ROS)水平,实时聚合酶链式反应仪检测结肠炎性因子水平以及TUNEL染色检测细胞凋亡。结果:DSS诱导结肠的长度显著缩短(P<0.05),肠道隐窝排列紊乱且表面不规则,杯状细胞数量减少,肠道紧密连接不完整,微绒毛稀疏;同时,DSS诱导ROS累积和炎性因子白细胞介素-1β(interleukin-1β,IL-1β)、IL-6和IL-10 mRNA水平极显著性上调(P<0.01),下调肿瘤坏死因子-αmRNA的表达(P<0.01),促进细胞凋亡(P<0.01)。然而,BA或5-ASA预处理均能逆转这一趋势,并且BA的作用效果优于5-ASA。结论:BA通过改善肠道结构的完整性,减少ROS产生和改善炎症反应,抑制细胞凋亡,从而对DSS诱导的结肠炎具有预防性的保护作用。Objective:To study the effect of betulinic acid(BA)on dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods:Eighty-four C57BL/6 mice were randomly divided into 7 groups,namely control,BA(0.5 mg/kg),DSS(4%by mass),low-,medium-and high-dose(0.25,0.5 and 1 mg/kg)BA+DSS,and 5-aminosalicylic acid(5-ASA)(50 mg/kg)+DSS groups.BA or 5-ASA was gavaged continuously for 14 days,and 4%DSS solution was consumed every day from the 8th day to induce colitis in mice for 7 consecutive days.Afterwards,the length of the colon was measured,the pathological changes and ultrastructure were observed by hematoxylin and eosin(H&E)staining and transmission electron microscopy,the level of reactive oxygen species(ROS)was measured by immunofluorescence staining,inflammatory factors were detected by real-time polymerase chain reaction(real-time PCR),and cell apoptosis was observed by TUNEL staining.Results:After DSS treatment,the length of the colon was significantly decreased(P<0.05),the arrangement of intestinal crypts became disordered with irregular surfaces,and the number of goblet cells was reduced,which was accompanied by incomplete intestinal tight junctions and sparse microvilli.Meanwhile,DSS induced the accumulation of ROS and significantly up-regulated the mRNA levels of the inflammatory cytokines interleukin-1β(IL-1β),IL-6,and IL-10(P<0.01),down-regulated the mRNA expression of tumor necrosis factor-α(P<0.01)in the colon,and promoted cell apoptosis(P<0.01).However,pretreatment with either BA or 5-ASA could reverse these phenomena,and the effect of BA was better than that of 5-ASA.Conclusion:BA has a preventive or protective effect against DSS-induced colitis by improving the integrity of intestinal structure,reducing ROS production,improving the inflammatory response and inhibiting apoptosis.

关 键 词：桦木酸 右旋糖酐硫酸钠 结肠炎 活性氧 细胞凋亡 

分 类 号：TS201.4[轻工技术与工程—食品科学]