基于PPARγ信号通路和T细胞免疫调节探讨戊己丸对炎症性肠病大鼠的治疗作用  

Exploration of Therapeutic Effect of Wujiwan on Inflammatory Bowel Disease in Rats Based on PPARγSignaling Pathway and T-cell Immunoregulation

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作  者:郭诗韵 郭雨轩 孙奕[1] 朱晓新[1] 李玉洁[1] 陈颖[1] 杨庆[1] 王娅杰[1] 李琦[1] 翁小刚[1] 邓志灏[2] GUO Shiyun;GUO Yuxuan;SUN Yi;ZHU Xiaoxin;LI Yujie;CHEN Ying;YANG Qing;WANG Yajie;LI Qi;WENG Xiaogang;DENG Zhihao(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Tongzhou Campus,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 101100,China)

机构地区:[1]中国中医科学院中药研究所,北京100700 [2]北京中医药大学东直门医院通州院区,北京101100

出  处:《中国实验方剂学杂志》2024年第23期237-245,共9页Chinese Journal of Experimental Traditional Medical Formulae

基  金:中国中医科学院科技创新工程项目(C12021A04911);北京市自然科学基金项目(M23012);国家自然科学基金项目(82174275)。

摘  要:目的:从过氧化物酶体增殖物激活受体γ(PPARγ)信号通路和T细胞免疫方面探讨戊己丸对大鼠炎症性肠病(IBD)的药效及药效机制,为中医药治疗IBD提供参考。方法:对35只大鼠采用2,4,6-三硝基苯磺酸(TNBS)灌肠诱导大鼠急性炎症性肠病,24 h后,模型动物分正常组、模型组、戊己丸给药组及阳性药组,各组连续灌胃给药8 d后解剖大鼠,比较大鼠结肠组织的疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)、脾脏指数;酶联免疫吸附测定法(ELISA)检测血清中白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平,实时荧光定量聚合酶链式反应(Real-time PCR)测定结肠组织中T-box家族的新型转录因子(T-bet)、Gata转录因子家族的转录因子3(Gata3)的mRNA表达水平;蛋白免疫印迹法(Western blot)检测大鼠结肠PPARγ、T-bet、核转录因子-κB p65(NF-κB p65)的蛋白表达水平。结果:IBD大鼠模型建造成功,且与模型组比较,戊己组大鼠DAI评分降低,CMDI评分降低(P<0.05),脾脏指数降低,血清中TNF-α含量显著降低(P<0.01),IL-10含量显著升高(P<0.01),结肠组织中T-bet mRNA含量升高,Gata3 mRNA含量明显升高(P<0.05),PPARγ蛋白表达量明显升高(P<0.05),T-bet、NF-κB p65蛋白表达明显降低(P<0.05,P<0.01)。结论:戊己丸可通过激活或上调IBD大鼠PPARγ的表达抑制促炎因子生成,参与炎症免疫进程,减轻炎症反应,作用机制与PPARγ调节NF-κB通路及增强Th2细胞转录表达、减少Th1细胞转录有关。Objective:This study explores the efficacy and pharmacological mechanism of Wujiwan in rats with inflammatory bowel disease(IBD)from the perspectives of the peroxisome proliferator-activated receptorγ(PPARγ)signaling pathway and T-cell immunity,providing reference for the treatment of IBD with traditional Chinese medicine.Method:The study involved administering 2,4,6-trinitrobenzenesulfonic acid(TNBS)enemas to 35 rats to induce acute IBD.After 24 hours,the animals were divided into the following groups:normal group,model group,Wujiwan treatment group,and positive drug control group.Each group received gastric gavage for 8 consecutive days before the rats were dissected to compare the disease activity index(DAI)of the rat colon tissue,the colon mucosal damage index(CMDI),and the spleen index.Enzymelinked immunosorbent assay(ELISA)was used to measure the levels of interleukin-1β(IL-1β),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α)in the serum.Quantitative real-time polymerase chain reaction(Real-time PCR)was used to determine the mRNA expression levels of T-bet(T-box expressed in T cells)and Gata3(Gata-binding protein-3)in the colon tissue.Western blot analysis was conducted to detect the protein expression levels of PPARγ,T-bet,and nuclear factor-κB p65(NF-κB p65)in the rat colon.Result:The rat model of IBD was successfully established.Compared with the model group,the Wujiwan treatment group showed reduced DAI,CMDI,and spleen index,decreased content of TNF-αin the serum(P<0.01),significantly increased content of IL-10(P<0.01),and elevated mRNA content of T-bet and Gata3(P<0.05)in the colon tissue.The expression of PPARγprotein was augmented(P<0.05),and the expression of T-bet and NF-κB p65 protein was decreased(P<0.05,P<0.01).Conclusion:Wujiwan activates or upregulates PPARγexpression in IBD rats to inhibit the generation of pro-inflammatory factors,participates in the inflammatory immune process,and alleviates inflammatory reactions.Its mechanism may involve regulating the NF-κB pathway

关 键 词:戊己丸 炎症性肠病 过氧化物酶体增殖物激活受体γ(PPARγ) T细胞 

分 类 号:R2-0[医药卫生—中医学] R33R289R574.4

 

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