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1.黑龙江中医药大学实验实训中心,哈尔滨 150040
2.黑龙江中医药大学药学院,哈尔滨 150040
张文娓,Email:wenwei0452@163.com,研究方向:中药经典名方效应机制及新药创制研究。
都晓伟,Email: xiaoweidu@hotmail.com。
收稿:2024-12-17,
修回:2025-04-10,
录用:2025-05-14,
纸质出版:2025-08-28
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张文娓,孟凡佳,闫丽莉,等.当归芍药散调控TLR4/MyD88/NF-κB信号通路减轻溃疡性结肠炎大鼠结肠损伤的机制研究[J].重庆医科大学学报,2025,50(8):1064-1070.
Zhang Wenwei,Meng Fanjia,Yan Lili,et al.Mechanism of Danggui Shaoyao powder regulating TLR4/MyD88/NF-κB signaling pathway to reduce colonic injury in ulcerative colitis rats[J].Journal of Chongqing Medical University,2025,50(8):1064-1070.
张文娓,孟凡佳,闫丽莉,等.当归芍药散调控TLR4/MyD88/NF-κB信号通路减轻溃疡性结肠炎大鼠结肠损伤的机制研究[J].重庆医科大学学报,2025,50(8):1064-1070. DOI: 10.13406/j.cnki.cyxb.003868.
Zhang Wenwei,Meng Fanjia,Yan Lili,et al.Mechanism of Danggui Shaoyao powder regulating TLR4/MyD88/NF-κB signaling pathway to reduce colonic injury in ulcerative colitis rats[J].Journal of Chongqing Medical University,2025,50(8):1064-1070. DOI: 10.13406/j.cnki.cyxb.003868.
目的
2
探究当归芍药散(Danggui Shaoyao powder,DGSYP)对溃疡性结肠炎(ulcerative colitis,UC)大鼠Toll样受体4(Toll-like receptor 4,TLR4)/髓样分化因子88(myeloid differentiation factor 88,MyD88)/核因子-κB(nuclear factor-κB,NF-κB)信号通路的影响。
方法
2
将48只SD雄性大鼠随机分为6组,正常组、模型组、DGSYP低剂量组(11.61 g/kg)、中剂量组(23.22 g/kg)、高剂量组(46.44 g/kg)及柳氮磺吡啶组(0.36 g/kg),每组8只。除正常组外,其余各组用5%三硝基苯磺酸钠(sodium trinitrobenzene sulfonate,TNBS)诱导,构建UC大鼠模型。成功建模后,各治疗组持续给药14 d,正常组与模型组给予等量生理盐水。计算大鼠疾病活动指数(disease activity index,DAI)评分;苏木素-伊红(hematoxylin-eosin,HE)染色,对大鼠结肠组织病理学变化展开观察。酶联免疫吸附测定(enzyme-linked immunosorbent assay,ELISA)结肠中白细胞介素(interleukin,IL)-6、IL-1β、肿瘤坏死因子-α(tumor necrosis factor α,TNF-α)含量。借助实时荧光定量聚合酶链式反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)和蛋白免疫印迹(Western blot,WB)检测结肠组织中TLR4、MyD88、NF-κB p65的mRNA和蛋白表达水平。
结果
2
对比正常组,模型组大鼠DAI评分上升,结肠缩短,组织病理变化明显,结肠组织中炎性因子IL-6、IL-1β、TNF-α水平明显升高(
P
<
0.01),TLR4、MyD88、NF-κB p65的mRNA和蛋白表达也明显提高(
P
<
0.05、
P
<
0.01)。与模型组相比,DGSYP各治疗组大鼠上述疾病相关状况均得到改善,DAI分数明显下降(
P
<
0.05),结肠增长,未见明显水肿或水肿程度减轻,结肠组织病理情况均有不同程度改善;炎性因子IL-6、IL-1β、TNF-α水平明显降低(
P
<
0.01),TLR4、MyD88、NF-κB p65的mRNA和蛋白表达水平明显下降(
P
<
0.05、
P
<
0.01)。
结论
2
DGSYP能够对TLR4/MyD88/NF-κB信号通路发挥调控作用,减少炎症因子释放量,缓解UC大鼠结肠炎性损伤程度。
Objective
2
To explore the effect of Danggui Shaoyao Powder(DGSYP) on the Toll-like receptor 4(TLR4)/Myeloid differentiation factor 88(MyD88)/Nuclear factor-κB(NF-κB) signaling pathway in ulcerative colitis(UC) rats.
Methods
2
Forty-eight male SD rats were randomly divided into 6 groups: normal group,model group,DGSYP low-dose group(11.61 g/kg),medium-dose group(23.22 g/kg),high-dose group(46.44 g/kg) and salazosulapyridine group(0.36 g/kg). There were 8 rats in each group. In addition to the normal group,the rats in other groups were induced by 5% sodium trinitrobenzene sulfonate(TNBS) to establish a UC rat model. After successful modeling,each drug treatment group continued to administer the intervention for 14 days. At the same time,the rats in the normal group and the model group were given equal volume of normal saline. The disease activity index(DAI) score was calculated.hematoxylin-eosin(HE) staining was used to observe the histopathological changes in the colon of rats. The levels of interleukin-6(IL-6),IL-1β,and tumor necrosis factor α(TNF-α) in colon tissue were measured by enzyme-linked immunosorbent assay(ELISA). Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR) was used to detect the mRNA expression levels of TLR4,MyD88 and NF-κB p65 in colon tissues. The expression levels of TLR4,MyD88 and NF-κB in colon tissues were detected by Western blot(WB).
Results
2
Compared with the normal group,the DAI score of the model group was increased,the colon was shortened,the histopathological changeswere obvious. The levels of inflammatory factors IL-6,IL-1β and TNF-α in colon tissue of model group were significantly increased(
P
<
0.01),the mRNA and protein expressions of TLR4,MyD88 and NF-κB p65 were also significantly increased(
P
<
0.05,
P
<
0.01). Compared with the model group,the above disease-related conditions of rats in each treatment group of DGSYP were improved to varying degrees,DAI fraction decreased significantly(
P
<
0.05),colon growth,no obvious edema or edema degree decreased,the histopathological changes of colon were improved to varying degrees. The levels of inflammatory factors IL-6,IL-1β and TNF-α in colon tissues were significantly decreased(
P
<
0.01),and the mRNA and protein expressions of TLR4,MyD88 and NF-κB p65 were significantly decreased(
P
<
0.05,
P
<
0.01).
Conclusion
2
DGSYP can regulate the TLR4/MyD88/NF-κB signaling pathway,thereby reducing the release of inflammatory factors,and then alleviating the degree of inflammatory damage in the colon of UC rats.
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