研究背景：糖尿病目前是世界流行疾病之一，會造成體內氧化壓力增加，器官功能衰退，甚至死亡。根據世界衛生組織統計每年約有三百萬人死於糖尿病。腫瘤壞死因子-α與細胞介白素-1β皆為細胞激素，主要功能是參與在發炎反應的過程中，目前也已知在糖尿病的發展病程中佔有重要角色。糖尿病患者常伴隨著腸胃道的疾病，包含腹瀉、嘔吐等。然而關於細胞激素與氧化壓力在糖尿病胃出血潰瘍的文獻卻相當缺乏。研究目的：本篇論文探討細胞激素與氧化壓力在糖尿病鼠胃出血潰瘍中所扮演的角色，以及pentoxifylline(PTX)、lysozyme chloride(LYZ)對於糖尿病鼠胃部的保護作用，並與胰島素的保護作用做比較；本研究利用streptozotocin(65mg/kg)以股靜脈注射誘發wistar大白鼠產生糖尿病，將糖尿病鼠與投與藥物組分別施予胃部以及迷走神經截斷手術，鼠胃以人工胃液灌流三小時後，將老鼠犧牲取出胃並進行觀察且測定胃黏膜各種參數並分析。實驗結果：糖尿病鼠胃部型態與組織切片及各種潰瘍參數(如：潰瘍面積、胃酸逆擴散現象、血紅素含量和組織胺濃度等)皆是呈現惡化的現象，且胃黏膜的腫瘤壞死因子-α與細胞介白素-1β含量皆增加、氧化壓力則有升高的情形；而再給予保護藥物PTX或LYZ之後潰瘍情形獲得改善，細胞激素含量也下降並有劑量依存的現象；給予胰島素的糖尿病鼠除了血糖有降低的情形外，潰瘍參數也都有下降的現象。糖尿病鼠細胞激素含量與胃潰瘍參數成中高度相關。結論：糖尿病的確造成大白鼠胃部有明顯的損傷及潰瘍，且在以人工胃液灌流三小時後胃部出血情形明顯，並伴隨著氧化壓力、組織胺增加、胃黏液減少、細胞激素釋出等症狀，而這些現象皆在投予保護藥物PTX或LYZ或給予胰島素降低血糖後獲得改善；且細胞激素含量與胃潰瘍參數成中高度相關的情形，顯示細胞激素的含量在糖尿病鼠胃出血潰瘍佔有重要的角色。

Background: Diabetes mellitus(DM) is a world widespread disease. This fatal disease can provoke oxidative stress and result in organ dysfunction. Cytokine, including tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β), are pro-inflammatory substances that may involve in the etiology of DM formation. Gastric damage is one of important manifestations in DM disease nevertheless, documents concerning with the influence of cytokines and oxidative stress in the formation of gastric hemorrhagic ulcer is lacking. Purpose: The aim of the present study is thus to investigate the role of cytokines and oxidative stress in the formation of gastric hemorrhage and ulcer in DM rats. Additionally, cytoprotective effects of pentoxifylline (PTX) and lysozyme chloride (LYZ) on gastric damage in DM rats were studied. Results: The results showed that the expression of TNF-α or IL-1β was increased in streptozotocin (STZ)-induced DM rat gastric mucosa. Moreover, high relationship of TNF-α and IL-1β generation to gastric hemorrhagic ulcer were found in those DM rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently attenuated by daily intragastric PTX and LYZ although blood glucose was not affected. Insulin decreased gastric ulcer, mucosal lipid peroxides and histamine levels while mucosal glutathione concentration was elevated. Conclusion: DM could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine production and pro-inflammation cytokines such as TNF-α and IL-1β release that could be ameliorated by PTX , LYZ and insulin in rats.

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