姜黄素对肥胖小鼠溃疡性结肠炎记忆性滤泡性T细胞的调控作用

Effects of curcumin on memory follicular T cells in obese mice with colitis

本研究在明确姜黄素有效治疗肥胖小鼠溃疡性结肠炎的基础上,评价其对结肠炎肥胖小鼠记忆性滤泡性T细胞(memory follicular T cells,mTf)的调控作用。经江西中医药大学实验动物伦理委员会审议同意并批准后,将40只瘦素突变型(ob/ob)雄性小鼠随机分为对照组、对照+姜黄素组、模型组和模型+姜黄素组,每组10只。采用葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导模型组和模型+姜黄素组小鼠建立慢性溃疡性结肠炎模型后,对照+姜黄素组和模型+姜黄素组小鼠灌胃给予姜黄素(200 mg·kg^(-1)·d^(-1))。麻醉处死小鼠,观察各组小鼠结肠质量、结肠质量指数、结肠长度等情况;HE染色后进行病理损伤评分;流式细胞术检测小鼠脾脏记忆性滤泡性辅助性T细胞(memory follicular helper T cells,mTfh)和记忆性滤泡性调节性T细胞(memory follicular regulatory T cells,mTfr)细胞亚群水平;酶联免疫吸附法检测结肠组织中白介素-10(interleukin-10,IL-10)和白介素-17A(interleukin-17A,IL-17A)的表达量。结果表明,姜黄素可明显增加结肠炎肥胖小鼠的体重和结肠长度,降低结肠重量、结肠质量指数和病理评分(P<0.05);并且姜黄素可显著降低中枢型记忆性滤泡性T细胞(central memory follicular T cells,cmTf)、mTfh1、mTfh17细胞水平和促炎细胞因子IL-17A含量(P<0.01),升高效应型记忆性滤泡性T细胞(effector memory follicular T cells,emTf)、mTfr细胞水平及抑炎细胞因子IL-10含量(P<0.05,P<0.01)。因此,姜黄素治疗肥胖小鼠结肠炎,可能是通过调控mTf细胞亚群平衡来实现的。

This study evaluated the regulatory effect of curcumin on memory follicular T cells(mTf)in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice.Forty male leptin mutant(ob/ob)mice were randomly divided into control group,control+curcumin group,dextran sodium sulfate(DSS)group and DSS+curcumin group,with 10 mice in each group.Mice in the DSS group and the DSS+curcumin group were induced by DSS to establish chronic ulcerative colitis model,and mice in the control+curcumin group and the DSS+curcumin group were given curcumin(200 mg·kg^(-1)·d^(-1))by intragastric administration.Mice were sacrificed under anesthesia,and colon mass index,colon length and other conditions were observed in each group.Pathological injury of colonic was performed after HE staining.The levels of memory follicular helper T cells(mTfh)and memory follicular regulatory T cells(mTfr)in spleen of mice were detected by flow cytometry.The expression levels of interleukin-10(IL-10)and interleukin-17A(IL-17A)in colon tissue were detected by ELISA.The results showed that curcumin significantly increased the body weight and colon length of obese mice with colitis,and decreased the colon weight,colon mass index and pathological score(P<0.05).Curcumin significantly reduced the levels of central memory follicular T cells(cmTf),mTfh1,mTfh17 cells and the content of pro-inflammatory cytokine IL-17A(P<0.01).The levels of effector memory follicular T cells(emTf)and mTfr and the content of anti-inflammatory cytokine IL-10 were increased(P<0.05,P<0.01).Therefore,curcumin may treat colitis in obese mice by regulating the balance of mTf cell subsets.