香参丸对结肠炎小鼠结肠黏膜TLR/NF-κB信号的调控作用  

Regulatory Effect of Xiangshenwan on TLR/NF-κB Signal in Colonic Mucosa of Mice with Colitis

作　　者：王梦雪 刘妙华 潘源乐 魏思逸 刘端勇[2] 黄小英[3] 赵海梅[4] WANG Meng-xue;LIU Miao-hua;PAN Yuan-le;WEI Si-yi;LIU Duan-yong;HUANG Xiao-ying;ZHAO Hai-mei(Graduate School of Jiangxi University of Chinese Medicine,Nanchang 330004,China;Prescription and Syndrome Research Center of Jiangxi University of Chinese Medicine,Nanchang 330004,China;Key Laboratory of Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China;College of Traditional Chinese Medicine,Jiangxi University of Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学研究生院,南昌330004 [2]江西中医药大学方证研究中心,南昌330004 [3]江西中医药大学,教育部重点实验室,南昌330004 [4]江西中医药大学中医学院,南昌330004

出　　处：《中国实验方剂学杂志》2021年第20期1-6,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82060838,82060799);江西省自然科学基金项目(20202ACBL206026,20192ACB20015,20202ACBL206028,20181BAB205082);江西省教育厅科技项目(GJJ196049,GJJ170733)。

摘　　要：目的:基于Toll样受体(TLR)/核转录因子-κB(NF-κB)经典信号通路,探究香参丸对葡聚糖硫酸钠(DSS)诱导的小鼠溃疡性结肠炎(UC)的作用及机制。方法:实验小鼠分为正常组,模型组,香参丸组,美沙拉嗪组。除正常组外,其余各组均自由饮用3%DSS溶液7 d以建立急性UC模型,从造模第1天至第10天连续予香参丸(5 g·kg^(-1))和美沙拉嗪(300 mg·kg^(-1))给药治疗,分别观察各组小鼠体质量,疾病活动指数(DAI),结肠质量,肠重指数,结肠长度,单位长度结肠质量和结肠病理改变以评价其疗效,同时蛋白免疫印迹法(Western blot)检测小鼠结肠组织内TLR5,髓样分化因子88(MyD88),白细胞介素-1受体相关激酶4(IRAK4),肿瘤坏死因子受体相关因子6(TRAF6),转化生长因子-β活化激酶1(TAK1),p38丝裂原活化蛋白激酶(MAPK),NF-κB,白细胞介素-1受体相关激酶1(IRAK1),转化生长因子-β活化激酶1结合蛋白1(TAB1),转化生长因子-β活化激酶1结合蛋白2(TAB2),丝裂原活化蛋白激酶激酶3(MKK3),丝裂原活化蛋白激酶激酶6(MKK6),环磷腺苷效应元件结合蛋白(CREB)蛋白表达。结果:与正常组比较,模型组小鼠体质量减轻,DAI评分升高,结肠质量,肠重指数和单位长度结肠质量升高,结肠长度缩短,结肠黏膜损伤严重,结肠组织TLR5,MyD88,IRAK4,TRAF6,TAK1,p38 MAPK,NF-κB,IRAK1,TAB1,TAB2,MKK3,MKK6,CREB蛋白表达均明显上升(P<0.05,P<0.01);与模型组比较,香参丸组和美沙拉嗪组小鼠体质量增加,DAI评分下降,结肠质量,肠重指数和单位长度结肠质量降低,结肠长度增加,结肠黏膜损伤程度好转,结肠组织TLR5,MyD88,IRAK4,TRAF6,TAK1,p38 MAPK,NF-κB,IRAK1,TAB1,TAB2,MKK3,MKK6,CREB蛋白表达明显下降(P<0.05,P<0.01)。结论:香参丸有效治疗DSS诱导的小鼠UC,可能与其抑制TLR/NF-κB信号通路有关。Objective: To explore the effect and mechanism of Xiangshenwan on ulcerative colitis(UC)induced by dextran sulfate sodium(DSS)in mice based on the classic Toll-like receptor(TLR)/nuclear factor kappa B(NF-κB)signaling pathway. Method:The experimental mice were divided into a normal group,a model group,a Xiangshenwan group,and a mesalazine group. The mice,except for those in the normal group, received 3% DSS solution for 7 days to establish the acute UC model and were treated with Xiangshenwan(5 g·kg^(-1))and mesalazine(300 mg·kg^(-1))continuously from the 1 st day to the 10 th day of modeling. The body weight,disease activity index(DAI),colon weight,intestinal weight index,colon length,colon weight per unit length, and pathological changes of mice were evaluated respectively. The protein expression of TLR5,myeloid differentiation factor 88(MyD88),interleukin-1 receptor-associated kinase 4(IRAK4),tumor necrosis factor receptor-associated factor 6(TRAF6),transforming growth factor β-activated kinase 1(TAK1),p38 mitogen-activated protein kinase(MAPK),NF-κB,IRAK1,TAK1-binding protein 1(TAB1), TAB2, mitogen-activated protein kinase kinase 3(MKK3), MKK6 and cyclic adenosine monophosphate response element-binding protein(CREB)in colon tissues of mice was detected by Western blot. Result: Compared with the normal group,the model group showed decreased body weight of mice,increased DAI scores,elevated colon weight,intestinal weight index,and colon weight per unit length,shortened colon length,severe colonic mucosal injury,and up-regulated protein expression of TLR5,MyD88,IRAK4,TRAF6,TAK1,p38 MAPK,NF-κB,IRAK1,TAB1,TAB2,MKK3,MKK6,and CREB in colon tissues(P<0.05,P<0.01). Compared with the model group,the Xiangshenwan group and the mesalazine group displayed increased body weight of mice,decreased DAI scores,declining colon weight,intestinal weight index,and colon weight per unit length,increased colon length,improved colonic mucosal injury,and downregulated protein expression of TLR5,MyD88,IRAK4,TRAF6,TAK1,p38 MAPK,NF

关 键 词：香参丸 溃疡性结肠炎 Toll样受体(TLR)/核转录因子-κB(NF-κB)通路 疗效评价 

分 类 号：R2-0[医药卫生—中医学] R22