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达原饮对Hp感染模型大鼠胃组织和口周皮肤TLR4/NF-κB/NLRP3通路的影响

Effect of Dayuan Decoction(达原饮)on TLR4/NF-κB/NLRP3 Pathway in Gastric Tissue and Perioral Skin of Model Rats with Hp Infection
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摘要 目的:观察达原饮对幽门螺杆菌(Hp)感染模型大鼠胃组织和口周皮肤Toll样受体4/核因子-κB/NOD样受体蛋白3(TLR4/NF-κB/NLRP3)信号通路,以及肿瘤坏死因子-α(TNF-α)与白细胞介素-1β(IL-1β)等炎症因子的影响,探讨达原饮治疗Hp感染的机制。方法:选取44只雄性SD大鼠,随机分为空白组8只及造模组36只,造模组予以Hp菌液灌胃造模,造模成功后,将造模组随机分为模型组、达原饮高剂量组、达原饮低剂量组、西药组,每组各8只,分别予以相应药物灌胃,空白组、模型组予以等量生理盐水灌胃,灌胃2周。观察大鼠造模前后一般情况改变,苏木精-伊红(HE)染色观察口周皮肤和胃组织病理学变化,酶联免疫吸附测定(ELISA)检测大鼠口周皮肤和胃组织TLR4、NF-κB、NLRP3表达以及血清中TNF-α、IL-1β表达水平。结果:给药干预后,与模型组相比,西药组、达原饮高剂量组、达原饮低剂量组大鼠皮毛柔顺光泽,饮食水量增加,大便逐渐成型,胃黏膜上皮细胞层次基本分明,排列较整齐,炎症细胞浸润减少,口周皮肤角化过度、棘层增厚、毛囊周围轻度炎症细胞浸润等情况均有不同程度改善。与模型组相比,西药组、达原饮高剂量组、达原饮低剂量组大鼠胃组织和口周皮肤TLR4、NF-κB、NLRP3蛋白表达水平均有不同程度的下调(P<0.05或P<0.01),血清炎症因子TNF-α、IL-1β表达明显下降(P<0.01)。结论:达原饮可能通过干预TLR4/NF-κB/NLRP3信号通路,抑制TLR4、NF-κB、NLRP3及下游炎症因子的表达,减轻Hp感染模型大鼠胃组织和口周皮肤炎症损伤。 Objective:To observe the effect of Dayuan Decoction(达原饮)on the Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3(TLR4/NF-κB/NLRP3)signaling pathway and inflammatory factors such as tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in the gastric tissue and perioral skin of model rats with Helicobacter pylori(Hp)infection,to explore the mechanism of Dayuan Decoction in treating Hp infection.Methods:Total forty-four male SD rats were randomly divided into the blank group(8 rats)and the modeling group(36 rats).The modeling group was administered Hp bacterial suspension via gastric tube injection to establish the model.After the modeling was established,the modeling group was randomly divided into the model group,the high-dose group of Dayuan Decoction,the low-dose group of Dayuan Decoction,and the Western medicine group,with 8 rats in each group.The blank group and the model group were administered an equal volume of normal saline via gastric tube injection,and the rats in other group were administered the corresponding drugs via gastric tube injection for 2 weeks.The changes in the general condition of the rats before and after the modeling were observed.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in the perioral skin and gastric tissue,and the enzyme linked immunosorbent assay(ELISA)was used to detect the expression of TLR4,NF-κB,NLRP3 in the perioral skin and gastric tissue of the rats and the expression levels of TNF-αand IL-1βin the serum.Results:After drug intervention,compared with the model group,the rats in the Western medicine group,high-dose group of Dayuan Decoction,and low-dose group of Dayuan Decoction had soft and shiny fur,increased appetite and water intake,gradually formed stool,and the epithelial cells of the gastric mucosa had clear layers and were arranged relatively neatly;The infiltration of inflammatory cells was reduced,and the conditions of keratinization overgrowth,thickening of the stratum corneum,and mild infiltration of inflammatory cells around the hair follicles in the perioral skin were all improved to varying degrees.Compared with the model group,the expression levels of TLR4,NF-κB,and NLRP3 proteins in the gastric tissue and perioral skin of the rats in the Western medicine group,high-dose group of Dayuan Decoction,and low-dose group of Dayuan Decoction were all downregulated to varying degrees(P<0.05 or P<0.01),and the expression of inflammatory factors such as TNF-αand IL-1βin the serum was significantly downregulated(P<0.01).Conclusions:By intervening TLR4/NF-κB/NLRP3 signaling pathway,Dayuan Decoction may inhibit the expression of TLR4,NF-κB,NLRP3 and downstream inflammatory factors,reduce the gastric tissue and perioral skin inflammatory damage in Hp infected rats.
作者 夏习林 张平 易园园 刘雪峰 XIA Xilin;ZHANG Ping;YI Yuanyuan;LIU Xuefeng(College of Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China)
出处 《山东中医药大学学报》 2024年第4期446-452,共7页 Journal of Shandong University of Traditional Chinese Medicine
基金 湖北省自然科学基金创新发展联合基金项目(编号:2024AFD293)。
关键词 达原饮 幽门螺杆菌 口周皮肤 胃组织 Toll样受体4/核因子-κB/NOD样受体蛋白3信号通路 炎症反应 大鼠 Dayuan Decoction(达原饮) Helicobacter pylori perioral skin gastric tissue Toll-like receptor 4/nuclear factor-κB/NOD-like receptor protein 3(TLR4/NF-κB/NLRP3)pathway inflammatory reaction rats
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