百秋李醇对幽门螺杆菌致小鼠胃炎的保护作用

目的: 探讨百秋李醇对幽门螺杆菌(Helicobacter pylori)感染小鼠胃炎的保护作用及其作用机制。方法: 采用化学致癌剂和幽门螺杆菌联合诱导法建立胃炎模型, 将C57BL/6小鼠分为正常组、模型组、阳性对照组(铋剂四联疗法)、百秋李醇高剂量组(40 mg·kg^-1)、百秋李醇低剂量组(20 mg·kg^-1)。灌胃给药, 连续治疗4周后, 行快速尿素酶试验, 评价胃组织中幽门螺杆菌的定植程度; 酶联免疫吸附法测定血清中白细胞介素8(IL-8)和肿瘤坏死因子α(TNF-α)浓度, 免疫组织化学法和实时定量聚合酶链反应法测定胃黏膜Wnt2、β联蛋白(β-catenin)及核因子κB(NF-κB)的蛋白及基因表达。结果: 各给药组小鼠胃黏膜的腺体排列、炎性细胞浸润及不典型增生等病变现象均有显著减轻, 百秋李醇高、低剂量组对幽门螺杆菌根除率分别为78%、70%, 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, 百秋李醇高、低剂量组小鼠血清IL-8和TNF-α水平均有显著降低(P＜0.01);与模型组相比, 百秋李醇高、低剂量组小鼠胃黏膜Wnt2、β-catenin和NF-κB蛋白及基因表达均有显著降低(P＜0.05或P＜0.01)。结论: 百秋李醇可通过抑制NF-κB信号转导通路及Wnt/β-catenin信号转导通路的持续活化及相关炎性细胞因子的高表达, 减轻胃黏膜炎症反应, 防止胃黏膜细胞上皮-间质样转化的发生, 从而阻止或延缓胃肠癌前病变的进程。

Protective effects of patchouli alcohol on Helicobacter pylori-induced gastritis in mice

OBJECTIVE To investigate the protective effects of patchouli alcohol on Helicobacter pylori-induced gastritis (HPG) in mice and its mechanism involved.METHODS Mice model of HPG was prepared by a combination of MNNG inducement and Helicobacter pylori infection. And then C57BL/6 mice were divided randomly into five groups, normal group, model group, positive (bismuth quadruple therapy) group, patchouli alcohol high dose (40 mg·kg^-1) and low dose (20 mg·kg^-1) groups. Drugs were orally administered for 4 weeks. Rapid urase test was carried out to evaluate the Helicobacter pylori colonization in mice. The IL-8 and TNF-α levels in sera were measured by ELISA. The protein and mRNA expression of Wnt2, β-catenin and NF-κB in gastric mucosa were examined by immunohistochemistry and RT-qPCR, respectively.RESULTS The pathological changes including gastric glandular disorder, inflammatory cell infiltration and atypical hyperplasia in mice with HPG were all significantly improved after the administration of drugs. Helicobacter pylori eradication rates in groups treated with 40 and 20 mg·kg^-1 of patchouli alcohol were 78% and 70%, respectively, which were evidently increased compared with that of model group (P < 0.01). The sera levels of IL-8 and TNF-α in groups administered with patchouli alcohol were all significantly decreased compared with those of model group (P < 0.01). Compared with model group, patchouli alcohol (40, 20 mg·kg^-1) evidently reduced the protein and mRNA expression of Wnt2, β-catenin and NF-κB in gastric mucosa of HPG mice (P < 0.05 or P < 0.01).CONCLUSION Oral administration of patchouli alcohol may show protective effects on gastric mucosa in HPG mice complicated with gastric precancerous lesions. The effectiveness of patchouli alcohol against HPG appears to be associated with the inhibition of NF-κB and Wnt/β-catenin signal pathways activation, down-regulation of inflammatory cytokines, improvement of gastric mucosa injuries caused by inflammatory reaction and prevention of epithelial-mesenchymal transition, etc.