Molecular Mechanisms Elucidating Why Old Stomach Is More Vulnerable to Indomethacin-Induced Damage than Young Stomach
Molecular Mechanisms Elucidating Why Old Stomach Is More Vulnerable to Indomethacin-Induced Damage than Young Stomach
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DOI：
10.1007/s10620-012-2314-1
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发表时间：
2012
影响因子：
3.1
通讯作者：
Hua Hong;Eun-Hee Kim;Ho J. Lee;Yoon Jae Kim;Jong Joon Lee;K. Hahm
中科院分区：
文献类型：
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作者：
Hua Hong;Eun-Hee Kim;Ho J. Lee;Yoon Jae Kim;Jong Joon Lee;K. Hahm
背景/目的虽然推测非类固醇抗炎药(NSAIDs)引起的胃损伤比幼年胃更易受非类固醇抗炎药(NSAIDs)诱导的胃损伤，但其潜在的潜在变化从未被探索过。方法为了研究NSAID引起胃损伤的分子机制，我们对6周龄和60周龄的大鼠分别给予消炎痛(0.1 mg消炎痛溶于1毫升羧甲基纤维素)。与年轻大鼠相比，老年大鼠的胃粘膜损伤显著增加(p<；(0.05)。服用消炎痛前，老年胃炎性介质包括细胞因子、趋化因子、蛋白酶和黏附分子均显著增加，服用消炎痛后，上述差异进一步增加(p<；P<0.05)。此外，老年大鼠胃组织中总氧化剂和凋亡执行子水平显著升高，脂氧素A4和抗凋亡蛋白Survivin、Bcl2水平显著降低。结论长期服用非甾体抗炎药的老年患者应考虑减少氧化还原激活或促炎介质的预防策略，以减少氧化还原激活或促炎介质的表达。
Background/AimsDetailed underlying changes have never been explored to explain how old stomach is more susceptible to non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastric damage than young stomach, although presumptively speculated as weakened mucosal defense system as well as attenuated regenerating capacity in old stomach.MethodsIn order to investigate molecular mechanisms relevant to NSAID-induced gastric damage, we administered indomethacin to 6-week-old and 60-week-old rats.ResultsIn spite of the same oral administration of indomethacin (0.1 mg indomethacin dissolved in 1 ml carboxyl methylcellulose) irrespective of body weights of rat, gastric mucosal damages were significantly increased in the older rats compared to the younger rats (p< 0.05). Before indomethacin administration, inflammatory mediators including cytokines, chemokines, proteases, and adhesion molecules were significantly increased in old stomach and these differences were further increased after indomethacin administration (p< 0.05). Furthermore, the levels of total oxidants and apoptotic executors were significantly increased in old stomach, whereas lipoxin A4 and anti-apoptotic proteins such as survivin and Bcl-2 were significantly decreased. Increased NF-κB-DNA binding activity as well as the activation of JNK and p38 was responsible for the increased expressions of inflammatory mediators as well as oxidants.ConclusionsA preventive strategy to reduce either redox activation or pro-inflammatory mediators should be considered in older patients taking long-standing NSAID administration.