胃黏膜保护剂的作用及其机制的研究

The effect and their mechanisms of gastric mucosal protective drugs.

目的 比较枸橼酸铋钾 1、枸橼酸铋钾 2及蔗糖硫酸酯碱式铝盐 (硫糖铝 )对胃黏膜的保护作用并研究作用机制。方法 采用乙醇、应激、阿司匹林及盐酸诱发大鼠胃黏膜急性损伤 ,用 5 0 %醋酸接触胃浆膜面产生慢性胃溃疡。枸橼酸铋钾 1、2和硫糖铝的急性损伤药物剂量分别为 37.5、40和335mg/kg。给药 3d ,每天 2次 ;慢性溃疡给药的剂量同急性损伤剂量 ,但给药 11d ,每天 2次。检查损伤指数及溃疡面积。结果 ①枸橼酸铋钾 1、枸橼酸铋钾 2和硫糖铝有抵抗乙醇、应激、阿司匹林和盐酸诱发的胃黏膜损伤作用 ,并促进醋酸溃疡的愈合。②这种保护黏膜、促进溃疡愈合的作用机制与增加胃黏膜血流量、增加胃黏膜的醌还原酶、谷胱甘肽S 转移酶 (GST)和谷胱甘肽还原酶 (GR)的活性及增加碱性成纤维生成因子 (bFGF)mRNA和诱导型一氧化氮合酶 (iNOS)mRNA的表达有关。结论 保护黏膜药枸橼酸铋钾 1、枸橼酸铋钾 2及硫糖铝有抵抗损伤 ,促进溃疡愈合的作用 ,其作用机制是增加胃黏膜血流量、减少氧自由基、增加bFGF及NOS。

Objective To compare the protective effect of colloidal bismuth subcitrate-1 (CBS-1, Lizudele), or colloidal bismuth subcitrate-2 (CBS-2, De-Nol) and sucralfate against gastric mucosal lesion and to investigate their mechanisms. Methods Gastric mucosal injury of rats was induced by ethanol, stress, aspirin and hydrochloric acid. Gastric ulcer was then induced by 50% acetic acid applied to the gastric tunica serosa. We observed the protective effects against gastric mucosal lesion and measured the injury index and the area of ulcer in each group. Statistical t test was used to compare the difference of each group. Results (1)CBS-1, CBS-2, and sucralfate had protective effect against lesions caused by ethanol, stress, aspirin and hydrochloric acid and could promote acetic acid-induced gastric ulcer healing. (2) The mechanisms of protective effect and ulcer healing promotion were that these drugs could increase gastric blood flow and increase activities of QR, GST and GR, and could also promote overexpression of bFGF mRNA and iNOS mRNA. Conclusion Gastric mucosal protective drugs, CBS and sucralfate had effect of resisting injury and promoting ulcer healing. The mechanisms were that they could increase gastric mucosal blood flow and the expression of bFGF mRNA and iNOS mRNA, and reduce oxygen free radical.