金合欢素调节NF-κB信号通路对幽门螺旋菌感染小鼠胃黏膜损伤的研究

The Effect of Acacetin on Gastric Mucosal Injury in Helicobacter Pylori-Infected Mice by Regulating NF-κB Signaling Pathway

目的:探讨金合欢素调节NF-κB信号通路对幽门螺旋菌(Hp)感染小鼠胃黏膜损伤的影响及机制。方法:C57BL/6小鼠以109 CFU/mL Hp(0.3mL)灌胃,并将建模成功小鼠随机分为Hp组、金合欢素低(金合欢素-L,30mg/kg)、高剂量(金合欢素-H,75mg/kg)组、阳性对照[奥美拉唑(400μg/kg)、克拉霉素(7.15mg/kg)及阿莫西林(14.25mg/kg)]组以及金合欢素-H+Prostratin(75mg/kg金合欢素+0.5mg/kg Prostratin)组,并以灌胃0.3mL生理盐水的小鼠为对照组,随后检测血清中胃肠激素[胃动素(MTL),胃饥饿素(Ghrelin),5-色羟胺(5-HT)]指标;分离胃组织,检测其病理学变化、评分,并检测组织中白细胞介素(IL)-1β、IL-10、肿瘤坏死因子(TNF)-α水平、闭锁蛋白(Occludin),闭锁小带蛋白(ZO-1)mRNA表达、细胞凋亡变化及凋亡蛋白Bax、Bcl-2、p-NF-kB p65、NF-kB p65表达。结果:与对照组相比,Hp组Ghrelin水平、IL-10水平、Occludin、ZO-1 mRNA表达、Bcl-2表达显著降低,MTL、5-HT水平、损伤评分、IL-1β、TNF-α水平、细胞凋亡率、Bax、p-NF-kB p65/NF-kB p65表达显著增加(P<0.05);与Hp组相比,金合欢素-L、金合欢素-H组、阳性对照组Ghrelin水平、IL-10水平、Occludin、ZO-1 mRNA表达、Bcl-2表达显著增加,MTL、5-HT水平、损伤评分、IL-1β、TNF-α水平、细胞凋亡率、Bax、p-NF-kB p65/NF-kB p65表达显著降低,不同金合欢素组间有差异(P<0.05);与金合欢素-H组相比,金合欢素-H+Prostratin组Ghrelin水平、IL-10水平、Occludin、ZO-1 mRNA表达、Bcl-2表达显著降低,MTL、5-HT水平、损伤评分、IL-1β、TNF-α水平、细胞凋亡率、Bax、p-NF-kB p65/NF-kB p65表达显著增加(P<0.05)。结论:金合欢素可通过NF-κB信号通路改善Hp感染小鼠胃黏膜损伤。

Objective:To investigate the effect of Acacetin on gastric mucosal injury in Helicobacter pylori(Hp)-infected mice by regulating NF-κB signaling pathway.Methods:C57BL/6 mice were given 109 CFU/mL Hp(0.3 mL)gavage,and the successfully modeled mice were randomly divided into Hp group,low Acacetin(Acacetin-L,30 mg/kg),high dose(Acacetin-H,75 mg/kg)group,positive control[omeprazole(400μg/kg),clarithromycin(7.15 mg/kg)and amoxicillin(14.25 mg/kg)]group,and Acacetin-H+Prostratin(75 mg/kg Acacetin+0.5 mg/kg Prostratin)group,and mice given 0.3 mL of normal saline by gavage were made the control group.Gastrointestinal hormones[motilin(MTL),Ghrelin,5-tryptamine(5-HT)]in serum were measured.Gastric tissue was isolated and the pathological changes and scores were detected.The levels of interleukin(IL)-1β,IL-10,tumor necrosis factor(TNF)-α,mRNA expression of occludin(Occludin),atresia band protein(ZO-1),apoptosis and the expression of apoptotic proteins Bax,Bcl-2,p-NF-kB p65 and NF-kB p65 were detected.Results:Compared with the control group,the Ghrelin level,IL-10 level,Occludin,ZO-1 mRNA expression and Bcl-2 expression in the Hp group were greatly reduced,the MTL,5-HT levels,damage score,IL-1β,TNF-αlevels,apoptosis rate,Bax,p-NF-kB p65/NF-kB p65 expression were greatly increased(P<0.05).Compared with the Hp group,the Ghrelin level,IL-10 level,Occludin,ZO-1 mRNA expression and Bcl-2 expression in the Acacetin-L,Acacetin-H group,positive control group were greatly increased,the MTL,5-HT levels,damage score,IL-1β,TNF-αlevels,apoptosis rate,Bax,p-NF-kB p65/NF-kB p65 expression were greatly reduced,there were differences among different Acacetin groups(P<0.05).Compared with the Acacetin-H group,the Ghrelin level,IL-10 level,Occludin,ZO-1 mRNA expression and Bcl-2 expression in the Acacetin-H+Prostratin group were greatly decreased,the MTL,5-HT levels,damage score,IL-1β,TNF-αlevels,apoptosis rate,Bax,p-NF-kB p65/NF-kB p65 expression were greatly increased(P<0.05).Conclusion:Acacetin can improve gastric mucosal injury in Hp infected mice through NF-κB signaling pathway.