芸香甙对应激性胃粘膜损伤保护作用的机制研究

Study of the protective mechanism of rutoside on the gastric mucosal injury induced by stress

目的初步研究芸香甙（Ｒｕ）对应激性胃粘膜损伤保护作用的机制。方法采用大鼠冷冻－束缚应激模型，评价胃粘膜损伤指数的变化。ＭＤＡ和ＧＳＨ含量测定分别应用ＴＢＡ和ＤＴＮＢ法，胃粘膜局部血流量（ＧＭＢＦ）测定应用氢气清除法。结果给予Ｒｕ抗溃疡剂量（５，２０ｍｇｋｇ－１，ｉｇ）ｂｉｄ，连续５ｄ，使血清和胃粘膜中因应激而升高的ＭＤＡ含量明显降低，并可升高应激后降低的胃粘膜ＧＳＨ含量。高Ｃａ２＋／低Ｃａ２＋分别可拮抗／增强Ｒｕ的胃粘膜保护作用。Ｒｕ尚可提高应激后降低的ＧＭＢＦ。Ｒｕ的构效关系研究显示，３个剂量（８．２，１６．４，３２．８μｍｏｌｋｇ－１）的Ｒｕ和槲皮素（ｑｕｅｒｃｅｔｉｎ，Ｑｕｅ）均可减轻应激所致的胃粘膜损伤，但Ｒｕ和Ｑｕｅ相同剂量组之间的胃粘膜损伤指数差异无显著性。结论Ｒｕ对应激性胃粘膜损伤保护作用的机制可能与其抗氧化作用、Ｃａ２＋拮抗和改善ＧＭＢＦ有关。Ｒｕ结构中的甙元部分在保护胃粘膜中起主要作用。

AIM To investigate primarily the protective mechanism of rutoside(Ru) on gastric mucosal injury induced by stress in rats. METHOD To use restraincold stress (RCS) model to evaluate the change of the index of gastric mucosal injury. The contents of MDA and GSH were determined by TBA and DTNB methods, respectively. The gastric mucosal blood flow (GMBF) was measured with hydrogen gas cleanrance method. RESULTS After giving antiulcer doses of Ru(5,20 mg·kg-1,ig) twice daily for 5 d, the MDA contents in gastric mucosa and blood serum which were elevated by RCS were decreased, while the reduced GSH contents were elevated. High/low level Ca2+ could inhibit/enhance the protective effects of Ru. Ru could increase the GMBF which was decreased by RCS. The study of structureactivity relationship of Ru showed that 3 doses (82,164,328 μmol·kg-1) of Ru or Quercetin (Que) all reduced the gastric mucosal injury by RCS, but there was no significant differences in injuryindex between two groups of same doses of Ru and Que. CONCLUSION This protective mechanism of Ru relates to antioxidative effect, Ca2+ inhibition and improving GMBF. The aglycone in the structure of Ru is important in this protective gastric mucosal effect.