18α甘草次酸对葡聚糖硫酸钠诱导小鼠急性溃疡性结肠炎的保护作用及机制研究  

The protective effect and mechanism of 18αglycyrrhetinic acid on acute ulcerative colitis induced by dextran sulfate sodium in mice

作　　者：张娟[1] 周萍[2] 穆先敏[3] Zhang Juan;Zhou Ping;Mu Xianmin(Department of Clinical Trials Center,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China;Department of Geriatrics,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China;Department of Biotherapy,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,China)

机构地区：[1]南京医科大学第二附属医院临床试验中心,南京210011 [2]南京医科大学第二附属医院老年医学科,南京210011 [3]南京医科大学第二附属医院生物治疗科,南京210011

出　　处：《中国医师杂志》2024年第2期234-239,共6页Journal of Chinese Physician

摘　　要：目的探究18α甘草次酸(18α-GA)对葡聚糖硫酸钠(DSS)诱导小鼠急性溃疡性结肠炎(UC)的保护作用,为18α-GA的临床应用提供理论依据和实验基础。方法将40只雄性C57BL/6J小鼠随机分为5组:DSS模型组,阳性药对照组,18α-GA高、中、低剂量组,每组8只,5组小鼠均采用3%DSS溶液连续喂养7 d建立急性UC动物模型,同时各组分别每天腹腔注射100 mg/kg生理盐水、100 mg/kg柳氮磺吡啶、40 mg/kg 18α-GA、20 mg/kg 18α-GA、10 mg/kg 18α-GA。每天测量并记录小鼠的体重,评估小鼠疾病活动指数(DAI)。第8天处死小鼠,取小鼠结肠测量其长度;切片观察结肠黏膜并进行病理学评分;蛋白免疫印迹法(Western blot)检测结肠组织中NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体通路相关蛋白表达;酶联免疫吸附试验(ELISA)测定结肠组织中IL-1β含量。结果与DSS模型组比较,18α-GA高、中剂量组第7天时的体重减轻幅度明显更小(均P<0.05);结肠长度更长(均P<0.05),结肠黏膜病理学评分明显更低(均P<0.05);结肠组织中GSDMD、cleaved-caspase1及IL-1β的表达显著更低(均P<0.05);18α-GA高剂量组DAI评分更低(P<0.05);结肠组织中NLRP3表达更低(P<0.05)。结论18α-GA可通过抑制NLRP3炎症小体通路的激活,改善DSS诱导的小鼠急性溃疡性结肠炎。Objective To explore the protective effect of 18αglycyrrhetinic acid(18α-GA)on acute ulcerative colitis(UC)induced by dextran sulfate sodium(DSS)in mice,providing theoretical and experimental basis for the clinical application of 18α-GA.Methods Forty male C57BL/6J mice were randomly divided into 5 groups:DSS model group,positive drug control group,high,medium,and low dose groups of 18α-GA,with 8 mice in each group.The 5 groups of mice were continuously fed with 3%DSS solution for 7 days to establish an acute UC animal model.At the same time,each group was intraperitoneally injected with 100 mg/kg physiological saline,100 mg/kg sulfasalazine,40 mg/kg 18α-GA,20 mg/kg 18α-GA,and 10 mg/kg 18α-GA daily.The weight of mice was measured and recorded daily,and the Disease Activity Index(DAI)of mice was evaluated.On the 8th day,the mice were euthanized and their colon length was measured;After slicing,the colon mucosa was observed and pathological scoring was performed;Western blot was used to detect the expression of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome pathway related proteins in colon tissue;Enzyme linked immunosorbent assay(ELISA)was used to determine the content of interleukin(IL)-1βin colon tissue.Results Compared with the DSS model group,the weight loss amplitude of the 18α-GA high and medium dose groups was significantly smaller on the 7th day(all P<0.05);Colon length was longer(all P<0.05),the pathological score of colon mucosa was significantly lower(all P<0.05);The expression of GSDMD,cleaved caspase1,and IL-1βin colon tissue was significantly lower(all P<0.05);The 18α-GA high-dose group had lower DAI scores(P<0.05);The expression of NLRP3 was lower in colon tissue(P<0.05).Conclusions 18α-GA can improve DSS induced acute ulcerative colitis in mice by inhibiting the activation of NLRP3 inflammasome pathway.

关 键 词：结肠炎 溃疡性 18α-甘草次酸 NLRP3蛋白 白细胞介素1Β 炎性肠疾病 

分 类 号：R574.62[医药卫生—消化系统]