加味半夏泻心汤拆方对幽门螺旋杆菌相关性胃炎小鼠的作用及机制研究OA北大核心CSTPCD
Effect and mechanism of modified Banxia Xiexin decoction disassembling prescriptions on mice with Helicobacter pylori-associated gastritis
目的:探讨加味半夏泻心汤拆方对幽门螺旋杆菌相关性胃炎小鼠的作用及机制.方法:40只SPF级雄性BALB/c小鼠随机分为空白对照组(n=6)和造模组(n=34),建立幽门螺旋杆菌相关性胃炎的脾胃湿热证小鼠模型,随机分为加味半夏泻心汤全方组、清热燥湿组、健脾和胃组、燥湿消痞组、模型组,每组 6 只.各组予相应药物灌胃,干预 4 周.观察并记录小鼠的一般生物学特征;酶联免疫吸附测定法(ELISA)检测小鼠血清白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)表达水平;采用苏木精-伊红(HE)染色和吉姆萨(Giemsa)染色以观察Hp定植情况及胃黏膜病理变化;实时荧光定量PCR法(qPCR)和免疫组织化学法(IHC)检测小鼠胃黏膜组织中核转录因子-κB(NF-κB)信号通路相关基因的mRNA及蛋白表达水平;qPCR法检测小鼠肠道乳酸杆菌(Lactobacillus)、双歧杆菌(Bifidobacterium)、肠杆菌(Enterobacteriaceae)、肠球菌(Enterococcus)含量.结果:与空白组相比,模型组小鼠饮食与饮水量减少,精神萎靡,活动量减少,胃黏膜组织病变严重,可见大量Hp定植,血清中IL-1β、IL-6、TNF-α表达水平升高(P<0.01),NF-κB p65 的mRNA和蛋白表达上调(P<0.01),而IκB-α的mRNA和蛋白表达下调(P<0.01),肠杆菌、肠球菌含量升高(P<0.01),而双歧杆菌和乳酸杆菌含量降低(P<0.01);与模型组相比,各治疗组小鼠一般状况及胃黏膜病变得到不同程度改善,Hp定植减少,血清中IL-1β、IL-6、TNF-α表达水平降低(P<0.05),NF-κB p65的mRNA和蛋白表达下调(P<0.05),IκB-α的mRNA和蛋白表达上调(P<0.05),肠杆菌、肠球菌含量降低(P<0.05),且在上述指标中全方组效果最好,拆方组中清热燥湿组优于健脾和胃组和燥湿消痞组,而双歧杆菌和乳酸杆菌含量升高(P<0.05),健脾和胃组优于燥湿消痞组和清热燥湿组.结论:加味半夏泻心汤能够抑制胃黏膜中幽门螺旋杆菌的定植,减轻胃黏膜组织损伤,可能与抑制NF-κB信号通路介导的炎症反应有关;能够促进肠道益生菌的生长,同时抑制有害菌的繁殖.清热燥湿药组在抑菌抗炎方面效果最佳,健脾和胃组药物在调和脾胃,增强人体免疫方面作用最优.全方配伍使用,发挥辛开苦降甘补的协同作用,充分体现中医学中"扶正驱邪,标本兼治"的治疗原则.
Objective:To investigate the effect and mechanism of the disassembled prescriptions of Modified Banxia Xiexin Decoction on Helicobacter pylori-associated gastritis in mice.Methods:Forty SPF-grade male BALB/c mice were randomly di-vided into the blank control group(n=6)and the model group(n=34).The mouse model of Helicobacter pylori associated gastri-tis with damp-heat syndrome of spleen and stomach was established and randomly divided into the Modified Banxia Xiexin Decoc-tion group,Qingrezaoshi group,Jianpihewei group,Zaoshixiaopi group and model group,with 6 mice in each group.Each group was given the corresponding drugs by gavage for 4 weeks.The general biological characteristics of mice were observed and record-ed;enzyme-linked immunosorbent assay(ELISA)was used to detect the expression levels of interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in the sera of mice;hematoxylin-eosin(HE)staining and Giemsa staining were used to observe Hp colonization and pathological changes of the gastric mucosa;quantitative real-time PCR(qPCR)and immuno-histochemistry were used to detect the mRNA and protein expression levels of genes related to the nuclear factor-κB(NF-κB)sig-naling pathway in the gastric mucosa tissues of mice;qPCR was used to detect the contents of Lactobacillus,Bifidobacterium,Enterobacteriaceae,and Enterococcus in the intestinal tracts of mice.Results:Compared with the blank group,the mice in the model group had a decrease in diet and water intake,listlessness,reduced activity,severe gastric mucosal tissue lesions,a large number of Hp colonization,increased serum expression levels of IL-1β,IL-6 and TNF-α(P<0.01),the mRNA and protein ex-pressions of NF-κB p65 were up-regulated(P<0.01),while the mRNA and protein expressions of IκB-α were down-regulated(P<0.01),the contents of Enterobacteriaceae and Enterococcus were increased(P<0.01),and the contents of Bifidobacterium and Lactobacillus were decreased(P<0.01);compared with the model group,the general condition and gastric mucosal lesions of the mice in each treatment group were improved to different degrees,the Hp colonization was reduced,the expression levels of IL-1β,IL-6 and TNF-α in serum were decreased(P<0.05),the mRNA and protein expressions of NF-κB p65 were down-regulated(P<0.05),and that of IκB-α were up-regulated(P<0.05),and the contents of Enterobacteriaceae and Enterococcus were decreased(P<0.05),and in the above indexes,the effect was the best in the whole formula group,and the Qingrezaoshi group was better than the Jianpihewei group and Zaoshixiaopi group in the disassembled group,while the content of Bifidobacterium and Lactobacil-lus was elevated(P<0.05),and the Jianpihewei group was superior to the Zaoshixiaopigroup and the Qingrezaoshi group.Conclu-sion:The Modified Banxia Xiexin Decoction can inhibit the colonization of Helicobacter pylori in the gastric mucosa and reduce the damage of the gastric mucosa,which may be related to the inhibition of the inflammatory response mediated by the NF-κB sig-naling pathway;and it can promote the growth of intestinal probiotic bacteria while inhibiting the reproduction of harmful bacteria.The Qingrezaoshi group has the best effect in the antibacterial and anti-inflammatory,and the Jianpihewei group plays a major role in regulating the spleen and stomach,and enhancing human immunity.The whole formula is used to play a synergistic effect of XinKai KuJiang GanBu,which fully reflects the treatment principle of"strengthening healthy Qi and eliminating pathogens,treat-ing both symptoms and root causes"in traditional Chinese medicine.
贾献玲;王海霞;邹佳辰;王学健;朱晶瑜
山东第二医科大学,山东 潍坊 261053山东第二医科大学,山东 潍坊 261053||山东第二医科大学附属医院,山东 潍坊 261031山东第二医科大学附属医院,山东 潍坊 261031
中医学
幽门螺杆菌相关性胃炎加味半夏泻心汤拆方炎症抑菌
Helicobacter pylori associated gastritisModified Banxia Xiexin DecoctionDisassembled prescriptionInflam-mationBacteria inhibition
《海南医学院学报》 2024 (016)
1210-1219 / 10
This study was supported by Co-construction of Science and Technology Project by the Science and Technology Department of the State Administration of Traditional Chinese Medicine(GZY-KJS-SD-2023-080) 国家中医药管理局科技司共建科技项目(GZY-KJS-SD-2023-080)
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