Gastroprotection Studies of Schiff Base Zinc (II) Derivative Complex against Acute Superficial Hemorrhagic Mucosal Lesions in Rats

BackgroundThe study was carried out to assess the gastroprotective effect of the zinc (II) complex against ethanol-induced acute hemorrhagic lesions in rats.Methodology/Principal FindingThe animals received their respective pre-treatments dissolved in tween 20 (5% v/v), orally. Ethanol (95% v/v) was orally administrated to induce superficial hemorrhagic mucosal lesions. Omeprazole (5.790×10−5 M/kg) was used as a reference medicine. The pre-treatment with the zinc (II) complex (2.181×10−5 and 4.362×10−5 M/kg) protected the gastric mucosa similar to the reference control. They significantly increased the activity levels of nitric oxide, catalase, superoxide dismutase, glutathione and prostaglandin E2, and decreased the level of malondialdehyde. The histology assessments confirmed the protection through remarkable reduction of mucosal lesions and increased the production of gastric mucosa. Immunohistochemistry and western blot analysis indicated that the complex might induced Hsp70 up-regulation and Bax down-regulation. The complex moderately increased the gastroprotectiveness in fine fettle. The acute toxicity approved the non-toxic characteristic of the complex (−5 M/kg).Conclusion/SignificanceThe gastroprotective effect of the zinc (II) complex was mainly through its antioxidant activity, enzymatic stimulation of prostaglandins E2, and up-regulation of Hsp70. The gastric wall mucus was also a remarkable protective mechanism.

背景：本研究旨在评估锌(II)配合物（zinc (II) complex）对乙醇（ethanol）诱导的大鼠急性出血性胃黏膜损伤的胃保护作用。
方法与主要结果：实验动物经口给予分别溶于5%体积分数吐温20（Tween 20）中的预处理药物。采用95%体积分数乙醇经口灌胃构建浅表出血性黏膜损伤模型。以奥美拉唑（Omeprazole，5.790×10⁻⁵ M/kg）作为阳性对照药。给予锌(II)配合物（2.181×10⁻⁵ M/kg和4.362×10⁻⁵ M/kg）进行预处理后，大鼠胃黏膜得到了与阳性对照组相当的保护效果。该配合物可显著升高一氧化氮（nitric oxide）、过氧化氢酶（catalase）、超氧化物歧化酶（superoxide dismutase）、谷胱甘肽（glutathione）及前列腺素E2（prostaglandin E2）的活性水平，并降低丙二醛（malondialdehyde）含量。组织学评估证实，该配合物通过显著减轻黏膜损伤、增加胃黏膜生成量发挥保护作用。免疫组化（immunohistochemistry）及蛋白质印迹（western blot）分析显示，该配合物可诱导热休克蛋白70（Hsp70）的表达上调及Bax基因的表达下调。该配合物在健康状态下可适度增强胃保护作用。急性毒性实验证实该配合物具有无毒性特征（给药剂量为−5 M/kg）。
结论与意义：锌(II)配合物的胃保护作用主要通过其抗氧化活性、促进前列腺素E2的酶促合成以及上调Hsp70表达实现。胃壁黏液的分泌也是其重要的保护机制之一。