高良姜黄酮组合物抑制PI3K/Akt通路对幽门螺杆菌胃炎小鼠的保护作用  

Protective Effect against Helicobacter pylor Gastritis in Mice by Flavonoid Combinations of Alpiniae Officinarum Rhizoma via Inhibition of PI3K/Akt Pathway

作　　者：罗鑫 郑吴殷晓 杨敬宇 詹健婷 马浩然 叶晓川 干国平 刘丹 LUO Xin;ZHENG Wuyinxiao;YANG Jingyu;ZHAN Jianting;MA Haoran;YE Xiaochuan;GAN Guopin;LIU Dan(Hubei Key Laboratory of Resource and Chemistry of Chinese Medicine,School of Pharmacy,Hubei University of Chinese Medicine,Wuhan 430065,China;Hubei Engineering Research Center for Traditional Chinese Medicine Processing,Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院中药资源与中药化学湖北省重点实验室,武汉430065 [2]湖北省中药炮制工程技术研究中心,武汉430065

出　　处：《中国实验方剂学杂志》2025年第8期61-68,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82173960,31400302)。

摘　　要：目的:探讨高良姜黄酮组合物对幽门螺杆菌(Helicobacter pylori)胃炎小鼠的保护作用及其机制。方法:健康SPF级C57BL/6J小鼠56只适应喂养1周后,所有小鼠灌胃混合抗生素,连续3 d。按照体质量随机分为正常组,模型组,阳性药组(三联治疗组),高良姜黄酮组合物低、高剂量组(100、200 mg·kg^(-1))。除正常组外各组通过灌胃H. pylori悬液建立H. pylori胃炎小鼠模型。造模成功后灌胃给药,每天1次,连续给药2周。苏木素-伊红(HE)染色观察胃组织病理学变化;快速尿素酶试纸检测H. pylori阳性率;采用银染色观察胃组织表面H. pylori附着情况;免疫组化法检测胃组织白细胞介素(IL)-8、髓样分化因子88(MyD88)蛋白的表达情况;酶联免疫吸附测定法(ELISA)检测胃组织中IL-6、肿瘤坏死因子-α(TNF-α)、IL-8和IL^(-1)β的含量;蛋白免疫印迹法(Western blot)检测磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)蛋白表达。结果:与正常组比较,模型组小鼠胃重系数降低、胃液pH升高、H. pylori感染率为100%,胃组织病理学显著改变。模型组小鼠胃组织中的IL-8、MyD88蛋白表达显著升高,小鼠血清中炎症因子水平IL-6、TNF-α、IL-8和IL^(-1)β均显著上调(P<0.01)。与模型组比较,高良姜黄酮组合物各治疗组小鼠胃重系数显著升高(P<0.01),胃液pH显著降低(P<0.01),H. pylori感染率显著降低,小鼠胃组织中的IL-8和MyD88蛋白表达显著降低(P<0.01),血清中IL-6、TNF-α、IL-8和IL^(-1)β炎症因子水平均显著降低(P<0.01),呈现剂量依赖性。高良姜黄酮组合物下调H. pylori胃炎细胞中PI3K和Akt蛋白的表达(P<0.01)。结论:高良姜黄酮组合物对H. pylori胃炎具有一定的保护作用,其机制与降低H. pylori感染率、调控PI3K/Akt相关信号通路抑制炎症因子释放相关。Objective:To investigate the protective effect and mechanism of action of flavonoid combination of Alpiniae Officinarum Rhizoma(A.officinarum)against Helicobacter pylori(H.pylori)gastritis in mice.Methods:After acclimatization for one week,56 SPF-grade healthy C57BL/6J mice were gavaged with mixed antibiotics for three consecutive days.They were randomly divided into a normal group,model group,positive drug group(triple therapy group),and low-and high-dose groups(100,200 mg·kg^(-1))of flavonoid combination of A.officinarum.The H.pylori gastritis mice model was established by gavage with H.pylori bacterial suspension in each group except for the normal group.After successful modeling,mice were administrated with corresponding drugs once a day for two weeks.Hematoxylin-eosin(HE)staining was used to observe the pathological changes in gastric tissue.Rapid urease test paper was used to detect the positive rate of H.pylori.Silver staining was used to observe the H.pylori adherence on the surface of gastric tissue.Immunohistochemistry was used to detect the protein expression of interleukin-8(IL)-8 and myeloid differentiation factor(MyD88)in gastric tissue.The serum levels of IL-6,tumor necrosis factor-α(TNF-α),IL-8,and IL^(-1)βwere detected by enzyme-linked immunosorbent assay(ELISA).The expressions of phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)protein were detected by Western blot.Results:Compared with those in the normal group,mice in the model group had lower gastric weight coefficients,higher pH of gastric juice,100%H.pylori infection rate,and significantly changed gastric histopathology.The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the model group were significantly elevated,and the serum levels of inflammatory factors IL-6,TNF-α,IL-8,and IL^(-1)βwere significantly up-regulated in mice.Compared with that in the model group,the gastric weight coefficient of mice in each treatment group of the flavonoid combinations of A.officinarum was elevated(P<0.01),and the pH of

关 键 词：幽门螺杆菌 幽门螺杆菌胃炎 高良姜 黄酮组合物 炎症因子 

分 类 号：R259[医药卫生—中西医结合] R285[医药卫生—中医内科学] R289[医药卫生—中医学]