小檗碱通过抑制凋亡和炎症减轻大鼠慢性萎缩性胃炎病变的效果  

Berberine Attenuates Chronic Atrophic Gastritis in Rats by Inhibiting Apoptosis and Inflammation

作　　者：田家豪 石悰悰 费素娟 TIAN Jiahao;SHI Congcong;FEI Sujuan(Department of Gastroenterology,the Affiliated Hospital of Xuzhou Medical University,Xuzhou 221000,China)

机构地区：[1]徐州医科大学附属医院消化内科,徐州221000

出　　处：《世界中医药》2023年第2期200-205,共6页World Chinese Medicine

基　　金：2021年江苏省科研与实践创新计划项目(SJCX21_1146)。

摘　　要：目的:探究小檗碱对慢性萎缩性胃炎(CAG)的改善作用及其作用机制。方法:将SD大鼠随机分为对照组、模型组、小檗碱低剂量组、小檗碱中剂量组、小檗碱高剂量组和DUSP19组,每组9只。除对照组外均构建CAG模型,小檗碱低、中、高剂量分别灌胃给与25、50、100 mg/kg的小檗碱,DUSP19组灌胃给与100 mg/kg的小檗碱和尾静脉注射JAK激酶2/信号转导及转录激活因子3(JAK2/STAT3)通路激活剂DUSP19100μmol/L。苏木精-伊红(HE)染色法检测病理学变化;蛋白质印迹法检测JAK2/STAT3信号通路及凋亡相关蛋白表达;酶联免疫吸附试验(ELISA)检测血清相关因子表达水平;原位末端转移酶标记技术(TUNEL)检测胃黏膜细胞凋亡。结果:与模型组比较,小檗碱观察组磷酸化JAK2(p-JAK2)、磷酸化JAK3(p-JAK3)、胃动素(MTL)、肿瘤坏死因子-α(TNF-α)、白细胞介素6(IL-6)、白细胞介素-1β(IL-1β)、前列腺素E 2(PGE 2)、内皮素(ET)、B淋巴细胞瘤-2相关X蛋白(Bax)、裂解胱天蛋白酶3(Cl-caspase-3)、裂解胱天蛋白酶9(Cl-caspase-9)水平及细胞凋亡率显著降低(P<0.05),胃泌素(GAS)、分泌型免疫球蛋白A(sIgA)、谷胱甘肽(GSH)、B淋巴细胞瘤-2(Bcl-2)水平显著升高(P<0.05);JAK2/STAT3通路激活剂DUSP19可显著扭转小檗碱对上述指标的影响(P<0.05),且HE结果显示小檗碱可显著改善CAG大鼠胃组织病理病变。结论:小檗碱可通过JAK2/STAT3信号通路抑制细胞凋亡和炎症反应减轻大鼠慢性萎缩性胃炎。Objective:To investigate the ameliorative effect of berberine on chronic atrophic gastritis(CAG)and its mechanism.Methods:SD rats were randomly divided into a control group,a model group,a low-dose berberine group,a medium-dose berberine group,a high-dose berberine group,and a DUSP19 group,with 9 rats in each group.Except the control group,CAG models were constructed.Berberine was given 25,50,and 100 mg/kg by gavage at low,medium,and high doses,respectively.The DUSP19 group was given 100 mg/kg of berberine by gavage and the tail vein was injected with 100μmol/L DUSP19,the protein tyrosine kinase 2/cytoplasmic transcription factor 3(JAK2/STAT3)pathway activator.The pathological changes were detected by hematoxylin-eosin(HE)staining.Western blot was used to detect the JAK2/STAT3 signaling pathway and apoptosis-related protein expression.Enzyme-linked immunosorbent assay(ELISA)was used to detect the expression level of serum-related factors.The apoptosis of gastric mucosa cells was detected by TdT-mediated dUTP Nick-End Labeling(TUNEL).Results:As compared with the model group,the levels of phosphorylated protein tyrosine kinase 2(p-JAK2),phosphorylated protein tyrosine kinase 3(p-JAK3),motilin(MTL),and tumor necrosis factor-α(TNF-α),interleukin 6(IL-6),and interleukin 1β(IL-1β),prostaglandin E 2(PGE 2),endothelin(ET),B-lymphoma toma-2 associated X protein(Bax),cystatin 3(Cl caspase-3),and cystatin 9(Cl caspase-9)and the cell apoptosis rate were significantly decreased(P<0.05),while the levels of gastrin(GAS),secretory immunoglobulin A(sIgA),glutathione(GSH),and B-lymphomatoma-2(Bcl-2)were significantly increased(P<0.05).DUSP19,the activator of JAK2/STAT3 pathway,significantly reversed the effect of berberine on the above indexes(P<0.05),and HE results showed that berberine significantly improved the pathological changes in gastric tissues in rats with CAG.Conclusion:Berberine can alleviate CAG in rats by inhibiting apoptosis and inflammation through the JAK2/STAT3 signaling pathway.

关 键 词：小檗碱 慢性萎缩性胃炎 JAK2/STAT3信号通路 信号通路 凋亡 炎症反应 病理病变 大鼠 

分 类 号：R285.5[医药卫生—中药学]