摘要
目的基于TLR4/NF-κB信号通路探讨托里消毒散治疗放射性直肠炎的作用机制。方法48只SD大鼠随机分为6组,除空白组外,其余各组均诱导造放射性直肠炎大鼠模型,造模成功后大鼠正常喂养3 d后开始灌肠,空白组、模型组以2 ml的0.9%生理盐水灌肠,阳性对照组以蒙脱石散(0.2 g/ml)联合地塞米松(1 mg/ml)2 ml灌肠,托里消毒散低(1 g/ml)、中(2 g/ml)、高剂量(4 g/ml)分别2 ml灌肠,每天1次,连续10 d。处死大鼠,测直肠直径,采用HE染色考察直肠组织病理学变化;ELISA检测血清干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)、IL-10、表皮生长因子(EGF)水平及血清免疫球蛋白IgA、IgM、IgG含量;Western blot检测直肠TLR4、Myd88、NF-κB p65、IκBα表达;qRT-PCR检测直肠TLR4、Myd88、NF-κBp65、IL-6、IL-10 mRNA表达。结果托里消毒散高剂量可改善直肠组织病理变化,降低直肠炎症评分(P<0.05);托里消毒散高剂量较模型组可升高大鼠血清中EGF、IL-4、IL-10、IgA、IgM、IgG水平(P<0.05),降低大鼠直肠组织IFN-γ、TNF-α、TLR4、Myd88、NF-κB p65、IκBα表达及TLR4、Myd88、NF-κB p65、IL-6 mRNA表达(P<0.01)。结论托里消毒散高剂量可改善放射性直肠炎大鼠的直肠组织病理学改变,对TLR4/NF-κB信号通路相关因子及炎性细胞因子的表达均具有一定作用。
Objective To explore the mechanism of modified Tuoli Xiaodu powder in the treatment of radiation proctitis based on TLR4/NF-κB signaling pathway.Methods Forty-eight SD rats were randomly divided into 6 groups,except for the control group,all the other groups were induced to make the rat model of radiation proctitis.After 3 d of normal feeding,the rats began enema,the control group and model group were enema with 2 ml 0.9%normal saline,and the positive control group were treated with 2 ml montmorillonite powder(0.2 g/ml)combined with dexamethasone(1 mg/ml)enema,modified Tuoli Xiaodu powder 2 ml enema with low(1 mg/ml),medium(2 mg/ml)and high dose(4 mg/ml)was performed once a day for 10 d.Then rats were killed,the diameter of rectum was measured,the histopathological changes of rectum were observed by HE staining,the levels of serum interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-10,epidermal growth factor(EGF)and IgA,IgM and IgG were measured by ELISA,the expressions of TLR4,Myd88,NF-κB p65,IκBαin rectum were detected by Western blot,and the expressions of TLR4,Myd88,NF-κB p65,IL-6 and IL-10 mRNA in rectum were detected by qRT-PCR.Results High dose of modified Tuoli Xiaodu powder could significantly im-prove the pathological changes of rectal tissue and reduce the score of rectal inflammation(P<0.05).Compared with the model group,the high dose of modified Tuoli Xiaodu powder could significantly increase the levels of ser-um EGF,IL-4,IL-10,IgA,IgM and IgG(P<0.05).The expression of IFN-γ,TNF-α,TLR4,Myd88,NF-κBp65,IκBαand TLR4,Myd88,NF-κBp65 and IL-6 mRNA significantly decreased in rats(P<0.01).Conclu-sion The high dose of modified Tuoli Xiaodu powder can significantly improve the pathological changes of rectum in rats with radiation proctitis and play a significant role in the expression of TLR4/NF-κB signaling pathway relat-ed factors and inflammatory cytokines.
作者
祝朝富
安佰平
黄洪婕
杜驰
吴勇俊
蓝兰
李丹
雷冬梅
李世杰
敖睿
Zhu Chaofu;An Baiping;Huang Hongjie(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610051)
出处
《安徽医科大学学报》
CAS
北大核心
2020年第9期1367-1373,共7页
Acta Universitatis Medicinalis Anhui
基金
四川省科技厅重点研发项目(编号:2017SZ0071)。
关键词
大鼠
放射性直肠炎
托里消毒散
信号通路
rats
radiation proctitis
modified Tuoli Xiaodu powder
signaling pathway
