Bilski J, Murty V L, Nadziejko C, Sarosiek J, Aono M, Moriga M, Slomiany A, Slomiany B L
Research Center, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark.
Digestion. 1988;41(1):22-33. doi: 10.1159/000199728.
The mechanism of gastric mucosal protection by an antiulcer agent, geranylgeranylacetone (GGA), against ethanol-induced injury was investigated. The experiments were conducted with groups of rats with and without intraperitoneal indomethacin pretreatment. Animals received intragastrically either a dose of GGA (200 mg/kg) or a vehicle, followed 30 min later by 1 ml of absolute ethanol. The rats were sacrificed after 30 min and the gastric mucosa was subjected to macroscopic and histologic assessment and the measurements of adherent mucus, its dimension and chemical composition. In the absence of GGA, ethanol produced advanced macroscopic necrosis (greater than 38%) and the extensive necrotic lesions were visible upon histologic examination. Pretreatment with GGA significantly reduced (p less than 0.001) the extent and depth of mucosal necrotic lesions caused by ethanol, and this protection was not thwarted by indomethacin. Evaluation of the adherent mucus and its dimension by Alcian blue uptake and inverted microscope technique revealed that GGA was also capable of preventing the untoward effect of indomethacin on the adherent gastric mucus gel and its thickness. Results of chemical analyses established that in the absence of GGA indomethacin caused an increase in mucus protein (15%) and a decrease in its covalently bound fatty acids (67%) and lipids (36%). The decrease in lipids was particularly reflected in the content of phospholipids. Indomethacin, however, had no apparent effect on the composition of gastric mucus elaborated in the presence of GGA. The results suggest that gastric mucosal protective action of GGA is not mediated by endogenous prostaglandins but rather appears to involve the metabolism of mucosal lipids.
研究了抗溃疡药物香叶基香叶基丙酮（GGA）对乙醇诱导的胃黏膜损伤的保护机制。实验在预先腹腔注射消炎痛和未注射消炎痛的大鼠组中进行。动物经胃给予一剂GGA（200mg/kg）或赋形剂，30分钟后再给予1ml无水乙醇。30分钟后处死大鼠，对胃黏膜进行大体和组织学评估，并测量黏附黏液、其尺寸和化学成分。在没有GGA的情况下，乙醇导致严重的大体坏死（超过38%），组织学检查可见广泛的坏死病变。GGA预处理显著降低（p<0.001）了乙醇引起的黏膜坏死病变的程度和深度，且这种保护作用不受消炎痛的影响。通过阿尔新蓝摄取和倒置显微镜技术评估黏附黏液及其尺寸，结果显示GGA还能够防止消炎痛对胃黏附黏液凝胶及其厚度产生不良影响。化学分析结果表明，在没有GGA的情况下，消炎痛导致黏液蛋白增加（15%），其共价结合脂肪酸减少（67%），脂质减少（36%）。脂质的减少尤其体现在磷脂含量上。然而，消炎痛对在GGA存在下产生的胃黏液组成没有明显影响。结果表明，GGA的胃黏膜保护作用不是由内源性前列腺素介导的，而是似乎涉及黏膜脂质的代谢。
