拉唑B防治大鼠胃溃疡的实验研究

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目的评价新型质子泵抑制剂拉唑B对大鼠胃溃疡模型的防治效果,并初步探讨其机制。方法在构建大鼠消炎痛、幽门结扎、水应激型溃疡模型之前,及构建慢性醋酸型溃疡模型(醋酸注射)之后灌胃不同剂量的拉唑B、雷贝拉唑(阳性对照)和0.5%甲基纤维素钠(空白对照),比较各组实验用大鼠的溃疡指数、溃疡抑制率或溃疡面积/体积的差异。实验用大鼠乙醚麻醉下行幽门结扎术,术时经十二指肠分别给予不同剂量的拉唑B、雷贝拉唑和0.5%甲基纤维素钠(对照)。处死动物后制备胃标本,收集胃液并测量体积,用0.1molNaOH滴定法测定胃液中HCl含量,测定胃蛋白酶活性。结果予不同剂量的拉唑B预处理后,消炎痛、幽门结扎、水应激各建模组大鼠胃溃疡指数/面积明显减少,且具有较好的剂量-效应关系,与雷贝拉唑相当,但与空白对照组差异明显(P<0.05或P<0.01)。拉唑B对消炎痛、幽门结扎、水应激型大鼠胃溃疡模型抑制半数有效量(ED50)依次为14.1、16.0和18.8μmol/kg。慢性醋酸型大鼠溃疡模型给予拉唑B后,溃疡面积明显减少,作用与雷贝拉唑相似。大鼠给予拉唑B后,胃酸分泌量明显减少(P<0.01),且有较好的剂量-效应关系;胃液量也明显减少(P<0.05或P<0.01);虽然单位体积胃蛋白酶活性未见变化,但由于胃液量减少,胃蛋白酶总活性明显降低(P<0.05或P<0.01);雷贝拉唑也有相似作用。结论拉唑B能有效防治消炎痛、幽门结扎、水应激等导致的大鼠胃溃疡,主要机制与其能够抑制胃酸分泌与胃蛋白酶活性有关。 Objective To evaluate the preventive and therapeutic effects of a new proton pump inhibitor, Lazolium B, on gastric ulcer model in rats and its mechanism. Methods Different doses of prazosin B, rabeprazole (positive control) and 0.5 (n = 2) were given before indomethacin, pyloric ligation, water stress ulcer model and chronic acetic acid ulcer model % Sodium methylcellulose (blank control), the ulcer index, the ulcer inhibition rate or the ulcer area / volume difference of the rats in each group were compared. Rats were anaesthetized with pyloric ligation in rats. Rats were administered lazole B, rabeprazole and 0.5% sodium methylcellulose (control) separately through the duodenum during operation. After the animals were sacrificed, the stomach specimens were prepared, the gastric juice was collected and the volume was measured. The content of HCl in the gastric juice was measured by titration with 0.1 mol NaOH, and the pepsin activity was measured. Results After pretreatment with different doses of Lazole B, the index / area of ​​gastric ulcer in rats in each group were significantly decreased, and the dose-effect relationship was better with rabeprazole But significant difference with the blank control group (P <0.05 or P <0.01). The inhibitory half-effective dose (ED50) of pyrazole B to indomethacin and pylorus ligation and water stress-induced gastric ulcer model were 14.1,16.0 and 18.8μmol / kg, respectively. Chronic acetic acid rat ulcer model given Lazole B, the ulcer area was significantly reduced, the role of rabeprazole and similar. After administration of Lazolobis, the gastric acid secretion was significantly decreased (P <0.01), and there was a better dose-effect relationship; gastric juice volume was also significantly reduced (P <0.05 or P <0.01); although the unit volume of pepsin activity No changes were observed, but the total pepsin activity was significantly reduced due to decreased gastric fluid volume (P <0.05 or P <0.01); rabeprazole also had similar effects. Conclusions Lazolium B can effectively prevent gastric ulcer in rats induced by indomethacin, pyloric ligation and water stress, and its main mechanism is related to its ability to inhibit gastric acid secretion and pepsin activity.
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