硫氧还蛋白-1在急性坏死性胰腺炎并急性胃黏膜损伤中的作用

目的探讨硫氧还蛋白-1（TRX-1）在实验性急性坏死性胰腺炎（ANP）并急性胃黏膜损伤发病机制中的作用以及抗氧化剂褪黑素对其的影响。方法72只大鼠随机分为对照组（C组，n=24）、ANP组（A组，n=24）和褪黑素干预组（M组，n=24）。A组分3次腹腔内注射6％L-精氨酸（L—Arg）1．5g／kg建立ANP模型；C组同法注射等量生理盐水；M组于首次注射L—Arg前0．5h腹腔内注射1％褪黑素50μg／kg。各实验组大鼠于末次腹腔内注射后6h、12h和24h分批处死。光镜下观察胰腺和胃组织并进行病理学评分，采用免疫组化检测TRX-1在胃黏膜的表达，并检测胃黏膜中MDA、MPO的含量。结果A组各时点胃黏膜TRX-1的染色积分及MDA、MPO的含量明显高于C组（P均〈0．05）；M组各时点胃黏膜中TRX一1的染色积分及MDA、MPO的含量明显低于A组（P均〈0．05），胰腺和胃组织病理改变较A组明显减轻（P均〈0．05）。结论内源性的TRX-1可能是胃黏膜组织抵御氧化应激损伤的重要因子之一，TRX-1的表达量可能与组织氧化应激损伤的严重程度有关。外源性的褪黑素在ANP时可能通过其抗氧化作用，减轻胃黏膜氧化应激损伤的程度，对胃黏膜有一定的保护作用。

Roles of Thioredoxin-1 in experimental acute necrotizing pancreatitis with acute gastric mucosa lesion

Objective To investigate the roles of Thioredoxin-1 （TRX-1） in acute necrotizing pancreatitis （ANP） with acute gastric mucosa lesion in rats, and to assess the effect of antioxidant melatonin on TRX-1 activity. Methods Seventy-two SD rats were randomly divided into control group （ group C, n = 24） , ANP group （ group A, n = 24） and melatonin intervention group （group M, n = 24）. In group A, the rats were injected intraperitoneally three times with 6 % L-Arginine （ 1.5 g/kg） in an interval of 1 hour for ANP. In group C, the rats received the same amount of saline at the same time. In group M, 1% melatonin （50 μg/kg） was administered intraperitoneally 0.5 hour before L-Arginine injection. Rats were killed at 6, 12 and 24 hours after the last intraperitoneal injection. The pathologic changes of pancreatic tissue and gastric tissue were observed under microscope. The expression of TRX-1 and the levels of MDA and MPO in gastric mucosa were detected by immunohistochemistry and biochemical analysis respectively. Results In group A, immunohistochemieal score of TRX-1 and the levels of MDA and MPO in gastric mucosa were higher than those in group C （P 〈 0.05 ）. In group M, immunohistochemical score of TRX-1 and the levels of MDA and MPO in gastric mucosa were lower than those in group A （P 〈 0.05） , and the pathologic changes of pancreatic tissue and gastric tissue were significantly improved （P 〈 0.05）. Conclusion Endogenous TRX-1 is an important factor to resist oxidative stress damage in gastric mucosa, the expression of TRX-1 in gastric mucosa may concerned with the level of oxidative stress damage. Ectogenic melatonin can decrease the level of oxidative stress damage in gastric mucosa by its antioxidation, and may prevent the pancreatic histologic damage and acute gastric mucosa lesion in L-Arginine induced ANP.