世界中医药

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DUSP19 100 μmol/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E2（PGE2）、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。

English Summary:

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 100 μ mol/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 E2(PGE2)，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.

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