藏药日官孜玛通过NF-κB信号通路对小鼠乙醇性胃溃疡的胃保护作用  

Gastroprotective Effect of Corydalis Hendersonii on Ethanolic Gastric Ulcer in Mice Via NF-κB Signaling Pathway

作　　者：完地高 安拉太 黄先菊[4] 郭肖 李啟恩 WAN Digao;AN Latai;HUANG Xianju;GUO Xiao;LI Qien(Tibetan Medical College,Qinghai University,Xining 810016,China;Tibetan Medicine Research Center,Qinghai University,Xining 810016,China;State Key Laboratory of Tibetan Medicine Research and Development,Xining 810016,China;School of Pharmaceutical Sciences,South-Central Minzu University,Wuhan 430074,China)

机构地区：[1]青海大学藏医学院,青海西宁810016 [2]青海大学藏医药研究中心,青海西宁810016 [3]藏药新药开发国家重点实验室,青海西宁810016 [4]中南民族大学药学院,湖北武汉430074

出　　处：《高原科学研究》2024年第1期92-101,共10页Plateau Science Research

基　　金：国家自然科学基金项目(31860585);青海省十大国家级科技创新平台培育建设项目(2023-ZJ-J05).

摘　　要：目的:通过灌胃无水乙醇建立小鼠乙醇性胃溃疡模型,研究日官孜玛总提物对小鼠乙醇性胃溃疡的保护作用。方法:随机将60只KM系小鼠分为空白对照组、模型组、奥美拉唑阳性组、日官孜玛总提物低、中、高剂量组,共6组每组10只。灌胃给药一周后,禁食不禁水24h,末次给药1.5h后,除空白对照组给同等体积的生理盐水外,其余五组按照体重灌胃0.1mL/10g的无水乙醇造模1h,建立小鼠乙醇性胃溃疡模型。造模1h后,取血取胃,计算乙醇性胃溃疡的损伤发生率及损伤抑制率,制备血清上层液和胃组织匀浆液,苏木精-伊红(HE)染色观察胃组织病理学变化;试剂盒检测血清中一氧化氮(NO)、超氧化物歧化酶(SOD)和胃组织中丙二醛(MDA)、髓过氧化物酶(MPO)的水平;实时荧光定量PCR(qRT-PCR)检测胃组织中p65、IKK-β、TNF-α和IL-1β的mRNA表达情况。结果:正常对照组小鼠胃黏膜光滑完整,无出血现象,其余各组小鼠均出现了黏膜出血、组织不同程度坏死。模型组小鼠胃损伤最为严重,表现为大块的出血面积,呈鲜红色。与正常组相比,模型对照组HE染色图表现为组织整体结构异常,黏膜层小面积坏死,黏膜下层结缔组织排列疏松,少见淋巴细胞浸润,血清中NO、胃组织中MDA、MPO及胃组织中p65、IKK-β、TNF-α和IL-1β的mRNA表达水平显著升高(P<0.05),血清中SOD水平降低(P<0.05);与模型组相比,阳性组和高、中、低剂量日官孜玛总提物给药组则表现为点状或条状出血,出血面积明显缩小、损伤发生率明显下降(P<0.05)、小鼠胃组织病理损伤有明显改善,血清、组织相关指标均出现不同程度的改善。结论:日官孜玛总提物能通过抑制NF-κB信号通路中关键基因p65、IKK-β、TNF-α和IL-1β的mRNA表达,抑制氧化应激和炎症反应,对小鼠乙醇性胃溃疡产生保护性作用。Objective The model of ethanolic gastric ulcer in mice was established by gavage of anhydrous etha-nol,and the protective effect of the total extract of Corydalis nepalensis on ethanolic gastric ulcer in mice was studied.Methods Sixty KM mice were randomly divided into six groups:blank control group,model group,omeprazole-positive group,and low-dose,medium-dose and high-dose groups of daily Guanzima total extract,with 10 mice in each group.After one week of gavage administration,fasting without water for 24 hours,and 1.5 hours after the last administration,except for the blank control group receiving the same volume of physiologi-cal saline,the other five groups were given 0.1 mL/10g anhydrous ethanol by gavage according to body weight for 1 hour to establish a mouse ethanol induced gastric ulcer model.After 1 hour of modeling,blood was taken from the stomach to calculate the incidence and inhibition rate of ethanol induced gastric ulcer injury.Serum su-pernatant and gastric tissue homogenate were prepared,and hematoxylin eosin(HE)staining was used to observe pathological changes in gastric tissue;The reagent kit detects the levels of nitric oxide(NO),superoxide dis-mutase(SOD)in serum,and malondialdehyde(MDA)and myeloperoxidase(MPO)in gastric tissue.The mRNA expression of p65,IKK-β,TNF-αand IL-1βin gastric tissues was detected by quantitative fluorescence PCR(qRT PCR).Results The gastric mucosa of mice in the normal control group was smooth and intact without hem-orrhage,while the mucosal hemorrhage and tissue necrosis of different degrees were observed in the remaining mice in all groups.The mice in the model group had the most severe gastric injury,which showed a large bleed-ing area with bright red color.Compared with the normal group,the HE staining map of the model control group showed abnormal overall tissue structure,small necrosis in the mucosal layer,loose arrangement of connective tissue in the submucosal layer,rare infiltration of lymphocytes,significantly higher mRNA expression levels of NO in ser

关 键 词：日官孜玛 乙醇性胃溃疡 NF-ΚB信号通路 氧化应激 

分 类 号：R29[医药卫生—民族医学]