Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis
Involvement of oxygen-derived free radicals in L-arginine-induced acute pancreatitis
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DOI：
10.1023/a:1018839821176
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发表时间：
1998-08-01
影响因子：
3.1
通讯作者：
Lonovics, J
中科院分区：
文献类型：
--
作者：
Czakó, L;Takács, T;Lonovics, J
本研究通过测定L-精氨酸（Arg）诱导的大鼠急性胰腺炎（AP）胰腺组织中丙二醛（MDA）、谷胱甘肽过氧化物酶（GPx）、过氧化氢酶（CAT）和超氧化物歧化酶（Mn-和Cu，Zn-SOD）的含量，以及黄嘌呤氧化酶抑制剂别嘌呤醇（Allopurinol）的保护作用，探讨氧自由基在AP发病中的作用。在雄性Wistar大鼠中，通过以1小时间隔腹膜内注射2 × 250 mg/100 g体重的精氨酸（20%的0.15 M NaCl溶液）诱导急性胰腺炎。对照组大鼠接受相同量的甘氨酸。别嘌呤醇，100或200 mg/kg，皮下注射前30分钟第一精氨酸注射。在Arg给药后6、12、24和45小时处死大鼠，通过血清淀粉酶水平升高和显微镜下观察到的典型炎症特征证实急性胰腺炎。血清淀粉酶水平在注射精氨酸后24小时达到高峰（30，800 +/-3813vs6352 +/-184units/L（对照组），48小时恢复正常，24小时组织MDA浓度显著升高，48小时达到峰值（5.00 +/- 1.75 vs 0.28 +/- 0.05 nM/mg蛋白质）。与对照组相比，注射Arg后6 h和12 h，过氧化氢酶和Mn-SOD活性显著降低，GPx活性显著降低，Cu，Zn-SOD活性显著降低。别嘌呤醇治疗显著降低血清淀粉酶升高（24小时为12.631 +/- 2.257单位/升），并防止组织MDA浓度升高（48小时为0.55 +/- 0.09 nM/mg蛋白质）。两种剂量的别嘌呤醇在Arg给药后48小时显著改善胰腺水肿、坏死和炎症。氧自由基在精氨酸诱导的急性胰腺炎的早期阶段产生。预防性别嘌呤醇治疗可防止活性氧代谢产物的产生，降低血清淀粉酶浓度，并对组织病理学变化的发展产生有益影响。
This study was aimed at an assessment of the role of oxygen-derived free radicals in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat, by measuring the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase, and superoxide dismutase (Mn- and Cu,Zn-SOD) in the pancreatic tissue, and evaluating the protective effect of the xanthine oxidase inhibitor allopurinol. Acute pancreatitis was induced in male Wistar rats by injecting 2 x 250 mg/100 g body weight of Arg intraperitoneally in a 1-hr interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. Allopurinol, 100 or 200 mg/kg, was administered subcutaneously 30 min before the first Arg injection. Rats were killed at 6, 12, 24, and 45 hr following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 hr after the Arg injection (30,800 +/- 3813 vs 6352 +/- 184 units/liter in the control) and normalized at 48 hr. The tissue concentration of MDA was significantly elevated at 24 hr and reached the peak value at 48 hr (5.00 +/- 1.75 vs 0.28 +/- 0.05 nM/mg protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 hr, and the Cu,Zn-SOD activity was significantly lower at 12 hr after the Arg injection as compared with the controls. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 units/liter at 24 hr) and prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM/mg protein at 48 hr). Both doses of allopurinol significantly ameliorated the pancreatic edema, necrosis, and inflammation at 48 hr after Arg administration. Oxygen-derived free radicals are generated at an early stage of Arg-induced acute pancreatitis. Prophylactic allopurinol treatment prevents the generation of reactive oxygen metabolites, reduces the serum amylase concentration, and exerts a beneficial effect on the development of histopathological changes.