腹水草抗大鼠乙醇型胃溃疡的作用及其对NO、iNOS和VEGF表达的影响

摘要

[目的]观察腹水草水提液抗大鼠乙醇型胃溃疡的作用效果，以及对一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）、和血管内皮生长因子（VEGF）表达的影响。[方法]48只SPF级SD大鼠随机分成正常对照组、模型组、雷尼替丁组，腹水草高、中、低剂量组，每组8只。正常对照组和模型组分别给予0.9%生理盐水灌胃；而雷尼替丁组则给予0.18%雷尼替丁混悬液灌胃（0.027g·kg-1·d-1）；腹水草各剂量组分别给予高、中、低剂量腹水草水提液灌胃（浓度分别为2.8、1.4、0.7 g·kg-1·d-1)，每天1次，连续14d。于最后1次灌胃1h后，采用无水乙醇造模1h。然后处死大鼠，比较各组大鼠胃溃疡指数及溃疡抑制率，分别采用硝酸还原酶法，夹心ELISA和荧光定量PCR法分析不同剂量腹水草水提液对NO含量、iNOS活力， VEGF蛋白，iNOS、VEGF mRNA表达的影响。[结果]腹水草水提液可以显著的抑制溃疡的发生。腹水草水提液高、中、低剂量给药组的溃疡抑制率分别为90.83%、70.26%、45.93%。与模型组相比，腹水草高剂量给药组大鼠胃黏膜组织中NO含量显著提高（P<0.01），腹水草各给药组大鼠胃黏膜组织中iNOS活力和iNOS mRNA的表达量均显著提高（P<0.01），而对于VEGF则无统计学差异。[结论]腹水草水提液具有显著地抗大鼠乙醇型胃溃疡的作用，其作用机制可能与提高胃组织中NO含量，iNOS活力及其mRNA的表达有关。%[Aim] To observe the antiulcer effect of the water extract of Veronicastrum axillare(Sieb. et Zucc) Yamazaki(VAY) on rats, and the effects of nitric oxide(NO), inducibie nitric oxide synthase(iNOS) and vascular endothelial growth factor(VEGF) expressions. [Method] Total y 48 SPF SD rats were random-ly divided into 6 groups, i. e. the normal group, the model group, the ranitidine group, the high dose VAY group, the medium dose VAY group and the low dose VAY group, 8 in each group. Rats in the normal group and the model group were respectively administered with 0.9%normal saline. Rats in the raniti-dine group were administered with 0.18%ranitidine suspension(at the daily dose of 0.027 g·kg-1) by gastrogavage. Those in the high dose VAY group, the medium dose VAY group and the low dose VAY group were administrated with VAY at the daily dose of 2.8g·kg-1, 1.4g·kg-1 and 0.7 g·kg-1 by gastrogav-age, once daily for 14 days successively. The gastric ulcer model was established using absolute ethanol after the last gastrogavage one hour later. The ulcer in-dex and ulcer inhibitory rate were compared in different groups after kil ing the rats. The NO concentration and iNOS vitality, the protein concentration of VEGF, mRNA expressions of iNOS and VEGF were respectively analyzed by nitrate reductase method, sandwich ELISA and real-time fluorescent quantita-tive PCR about the effects of different doses VAY. [Results] The water extract of VAY could significantly restrain gastric ulcer. The ulcer inhibitory rate of high, middle and low dosage group were respectively 90.83%,70.26%,45.93%. Compared with model group, NO concentration in high dose VAY group in-creased significantly(P<0.01), iNOS vitality and iNOS mRNA expressions in al VAY groups both promoted significantly( P<0.01), but it had no statistical y significant differences on VEGF. [Conclusion] Water extract of VAY had significant effects against gastric ulcer induced by absolute ethanol in rats. The mechanism of VAY might relate to improving NO concentration, iNOS vitality and promoting mRNA expressions.