Yagci Gokhan, Gul Husamettin, Simsek Abdurrahman, Buyukdogan Varol, Onguru Onder, Zeybek Nazif, Aydin Ahmet, Balkan Mujdat, Yildiz Oguzhan, Sen Dervis
Department of General Surgery, Gulhane Military Medical Academy, Etlik, Ankara, Turkey.
J Gastroenterol. 2004;39(3):268-76. doi: 10.1007/s00535-003-1287-4.
Acute pancreatitis (AP) is a complex disease associated with significant complications and a high rate of mortality. Although several mechanisms are put forward, oxidative stress seems the most important early event in the pathophysiology of AP. Therefore, we evaluated the beneficial effects of N-acetylcysteine (NAC), a strong antioxidant, in experimental AP.
Forty-nine Sprague-Dawley rats were used. Acute pancreatitis (AP) was induced by the intraductal infusion of sodium taurocholate. Rats were divided into seven groups (each containing seven rats): control, sham-operated (saline-treated, 3.5 and 12 h), non-treated AP (3.5 and 12 h) and NAC-treated AP (3.5 and 12 h). Treated rats received intraperitoneal (i.p.) NAC 1000 mg/kg 24 h before and just before the induction of pancreatitis.
Rats with AP had extensive parenchymal and fat necrosis and NAC treatment at 12 h reduced tissue necrosis significantly (P < 0.05). NAC treatment at 12 h reduced leukocytic infiltration significantly (P < 0.05). Edema and hemorrhage were significantly increased in the AP groups when compared to controls (P < 0.001). NAC treatment reduced edema and hemorrhage at both 3.5 and 12 h slightly but not significantly. The total pathological mean score was significantly increased in the AP groups (P < 0.05) and it was reduced by NAC treatment (P < 0.05). NAC treatment decreased plasma amylase and lipase levels significantly (P < 0.05). While glutathione peroxidase (GPx) activity of pancreatic tissue was similar in the NAC-treated and AP groups, hepatic tissue GPx activity was lower in the AP groups, and NAC treatment restored it (P < 0.05). NAC had no effect on pancreatic superoxide dismutase level. In the NAC-treated rats, the serum NO(2)/NO(3) (nitrite/nitrate) level was significantly increased in the 3.5-h group when compared to the respective AP group (P < 0.05). NAC treatment also significantly reduced the serum concentration of the lipid peroxidation product, malondialdehyde, at 12 h (P < 0.05).
NAC treatment had beneficial effects in sodium taurocholate-induced AP in rats. It reduced pancreatic tissue necrosis and lipid peroxidation. In our study, the mechanism underlying the beneficial effects of NAC seemed to be its antioxidant activity, either by increasing hepatic GPx activity, or by a direct scavenging effect on free radicals, thus enhancing the production of and/or inhibiting the degradation of nitric oxide.
急性胰腺炎（AP）是一种复杂疾病，伴有严重并发症和高死亡率。尽管提出了多种机制，但氧化应激似乎是AP病理生理学中最重要的早期事件。因此，我们评估了强力抗氧化剂N-乙酰半胱氨酸（NAC）在实验性AP中的有益作用。
使用49只Sprague-Dawley大鼠。通过经导管注入牛磺胆酸钠诱导急性胰腺炎（AP）。大鼠分为七组（每组七只）：对照组、假手术组（生理盐水处理，3.5小时和12小时）、未处理的AP组（3.5小时和12小时）以及NAC处理的AP组（3.5小时和12小时）。处理组大鼠在诱导胰腺炎前24小时及即将诱导胰腺炎时腹腔注射（i.p.）1000 mg/kg的NAC。
AP大鼠出现广泛的实质和脂肪坏死，12小时时NAC处理显著减轻了组织坏死（P < 0.05）。12小时时NAC处理显著减少了白细胞浸润（P < 0.05）。与对照组相比，AP组的水肿和出血显著增加（P < 0.001）。NAC处理在3.5小时和12小时时均轻微减轻了水肿和出血，但不显著。AP组的总病理平均评分显著增加（P < 0.05），而NAC处理使其降低（P < 0.05）。NAC处理显著降低了血浆淀粉酶和脂肪酶水平（P < 0.05）。虽然NAC处理组和AP组胰腺组织的谷胱甘肽过氧化物酶（GPx）活性相似，但AP组肝组织的GPx活性较低，而NAC处理使其恢复（P < 0.05）。NAC对胰腺超氧化物歧化酶水平无影响。在NAC处理的大鼠中，3.5小时组的血清NO(2)/NO(3)（亚硝酸盐/硝酸盐）水平与相应的AP组相比显著升高（P < 0.05）。NAC处理在12小时时也显著降低了脂质过氧化产物丙二醛的血清浓度（P < 0.05）。
NAC处理对牛磺胆酸钠诱导的大鼠AP有有益作用。它减轻了胰腺组织坏死和脂质过氧化。在我们的研究中，NAC有益作用的潜在机制似乎是其抗氧化活性，要么通过增加肝GPx活性，要么通过对自由基的直接清除作用，从而增强一氧化氮的产生和/或抑制其降解。
