苦参碱治疗慢性萎缩性胃炎的实验研究  

Protective effects of matrine against experimental chronic atrophic gastritis in rats

作　　者：才真[1] 何占坤 邹江[2] 王东强[3] CAI Zhen;HE Zhan-kun;ZOU Jiang;WANG Dong-qiang(Department of Pharmacy,First Central Municipal Hospital,Tianjin 300192,China;Department of Gastroenterology,First Central Municipal Hospital,Tianjin 300192,China;Department of Integrated TCM&Western Medicine,First Central Municipal Hospital,Tianjin 300192,China)

机构地区：[1]天津市第一中心医院药学部,天津300192 [2]天津市第一中心医院消化科,天津300192 [3]天津市第一中心医院中西医结合科,天津300192

出　　处：《中国医院药学杂志》2021年第14期1400-1404,1422,共6页Chinese Journal of Hospital Pharmacy

基　　金：天津市卫生健康委员会天津市中医药管理局中医中西医结合科研课题(编号:2019097);全国中药特色技术传承人才培训项目(编号:T20184828005)。

摘　　要：目的:探讨苦参碱对大鼠慢性萎缩性胃炎(CAG)的影响及其作用机制。方法:采用多因素复合法建立CAG模型,将大鼠分为正常组、模型组、阳性对照组(维酶素300 mg·kg^(-1))、苦参碱高剂量组(200 mg·kg^(-1))、苦参碱低剂量组(100 mg·kg^(-1)),每组10只。灌胃给药,连续治疗8周后,于光镜下观察胃黏膜组织病理学并进行病理程度分级;放射免疫法测定血清胃泌素(GAS)和血浆生长抑素(SS)含量;酶联免疫吸附法测定胃黏膜匀浆液中白细胞介素Iβ(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)浓度,实时定量聚合酶链反应法测定胃黏膜Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子κB(NF-κB)基因表达。结果:各给药组大鼠胃黏膜病变有显著减轻,炎性细胞浸润程度和固有腺体萎缩程度的组间差异均有统计学意义(P<0.01);与模型组相比,苦参碱高、低剂量组大鼠血清GAS含量显著升高(P<0.01),血浆SS含量则出现显著降低(P<0.01);苦参碱高、低剂量组大鼠胃黏膜IL-1β、IL-6和TNF-α水平均有显著降低,与模型组相比组间差异均有统计学意义(P<0.01);与模型组相比,苦参碱高剂量组大鼠胃黏膜TLR4、MyD88和NF-κB mRNA相对表达量均有显著降低(P<0.05或P<0.01),苦参碱低剂量组TLR4和NF-κB mRNA相对表达量均有显著降低(P<0.05或P<0.01)。结论:苦参碱可通过抑制TLR4/MyD88/NF-κB信号转导通路的持续活化及相关炎症细胞因子的高表达,减轻CAG炎症反应,阻止炎症细胞对胃黏膜造成的损伤,发挥对胃黏膜的保护作用。OBJECTIVE To explore the protective effects of matrine on chronic atrophic gastritis(CAG)in rats and elucidate its underlying mechanism.METHODS Rat model of CAG was established by N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)inducing,ranitidine dosing,ethanol load and dietary irregularity,etc.Then rats were divided randomly into five groups of normal,model,positive(vitacoenzyme 300 mg·kg^(-1)),high-dose matrine(200 mg·kg^(-1))and low-dose matrine(100 mg·kg^(-1))(n=10 each).Drugs were orally administered for 8 weeks.The histopathology of gastric mucosa was observed and graded under light microscope.The serum level of gastrin(GAS)and the plasma level of somatostatin(SS)were detected by radioimmunoassay.The levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in gastric mucosa homogenate were measured by enzyme-linked immunosorbent assay(ELISA).And the expressions of TLR4,MyD88 and NF-κB mRNA in gastric mucosa were examined by real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS Inflammatory cell infiltration and gastric glandular atrophy all significantly improved in drug-dosing group as comparing with model group(P<0.01).Compared with those of model group,serum GAS levels in groups treated with matrine(200 and 100 mg·kg^(-1))evidently increased(P<0.01)while plasma SS level decreased markedly(P<0.01).The levels of IL-1β,IL-6 and TNF-αin gastric mucosa homogenate in groups administered with matrine all declined markedly as comparing with those of model group(P<0.01).As compared with those of model group,matrine(200 and 100 mg·kg^(-1))evidently lowered the expressions of TLR4 and NF-κB mRNA in gastric mucosa(P<0.05 or P<0.01)and matrine(200 mg·kg^(-1))markedly lowered the expression of MyD88 mRNA(P<0.05).CONCLUSION Oral dosing of matrine may show a protective effect on gastric mucosa of CAG rats.The effectiveness of matrine against CAG appears to be associated with a suppression of TLR4/MyD88/NF-κB signal pathway activation,a down-regulation of inflammatory cyt

关 键 词：苦参碱 慢性萎缩性胃炎 炎症反应 TLR4/MyD88/NF-κB信号转导通路 

分 类 号：R967[医药卫生—药理学]