硫化氢在慢性不可预测应激性胃损伤中的作用。

M. Tohamy, M. Ghalwash, N. Abo-Elmaaty, Refka Messiha, Samah Fouad
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摘要

本研究的目的是探讨硫化氢对慢性不可预测应激(CUS)诱导的胃损伤可能的保护作用。材料与方法:将40只大鼠分为4组:对照组、应激组、应激+氨基乙酸(AOAA) (H2S合成抑制剂);50毫克/公斤/ 48小时;IP)、应激+氢硫化钠(NaHS) (H2S供体,5mg/kg/48h;IP)。在所有暴露于CUS的组中,一组慢性不可预测的应激源按随机顺序施加6周。实验方案结束时采集血液、胃内容物和胃组织样本。用肉眼和显微镜观察胃组织病理变化。测定胃内容物pH值、血清丙二醛水平、全血谷胱甘肽水平。免疫组织化学检测凋亡标志物Caspase-3和抗凋亡标志物BCL-xl的表达。结果:在所有暴露于CUS的组中,胃pH值明显降低,宏观和显微镜检查可见胃浅表至深部溃疡的一系列病变。血清丙二醛水平显著升高,抗氧化GSH水平显著降低。在所有应激大鼠中,Caspase-3的表达均显著升高,而抗凋亡蛋白BCL-xl的表达均显著降低。AOAA加重了这些症状,而NaHS则改善了这些症状。结论:提高H2S的生物利用度可能对CUS诱导的胃损伤具有保护作用。结果表明,这种保护作用可能是通过抗氧化和抗凋亡作用实现的。
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The Role of Hydrogen Sulfide in Chronic Unpredictable Stress-Induced Gastric Lesions.
The aim of this study was to investigate the possible protective role of Hydrogen sulfide on chronic unpredictable stress (CUS) -induced gastric lesions. Materials and methods: 40 rats were divided into 4 groups: control group, stressed rats group, stressed + Aminooxyacetic acid (AOAA) (inhibitor of H2S synthesis; 50mg/kg/48hour; IP), stressed + Sodium hydrosulfide (NaHS) (donor of H2S, 5mg/kg/48hour; IP). In all the groups exposed to CUS, a set of chronic unpredictable stressors was applied for 6 weeks in random order. At the end of experimental protocol blood samples, gastric content and gastric tissues samples were collected. Gastric tissues histopathological changes were evaluated by macroscopic and microscopic examination. Gastric content pH, serum MDA level, whole blood GSH level were estimated. Expression of Caspase-3 (apoptotic marker) and BCL-xl (anti-apoptotic marker) was assessed by immunohistochemistry. Results: In all the groups exposed to CUS, there was a significant reduction in gastric pH value and a range of gastric lesions ranging from superficial to deep ulceration as evident by macroscopic and microscopic examination. Also, there was significant elevation in MDA serum level and significant reduction in anti-oxidant GSH blood level. In all stressed rats, the expression of Caspase-3 was significantly higher whereas a significant decrease in expression of anti-apoptotic protein BCL-xl was observed. These findings were aggravated by AOAA while using NaHS improved them. Conclusion: it seems that increasing bioavailability of H2S could have a protective role against CUS induced gastric lesions. The results suggest that this protection could be through anti-oxidant and anti-apoptotic effects.
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