急性坏死性胰腺炎大鼠中核因子-κB对活性氧的激活作用
Nuclear factor-kappaB activation on the reactive oxygen species in acute necrotizing pancreatitic rats.
作者信息
Long Jin, Song Na, Liu Xi-Ping, Guo Ke-Jian, Guo Ren-Xuan
机构信息
Department of Surgery, The First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China.
出版信息
World J Gastroenterol. 2005 Jul 21;11(27):4277-80. doi: 10.3748/wjg.v11.i27.4277.
AIM
To investigate the potential role of nuclear factor kappa-B (NF-kappaB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-kappaB).
METHODS
Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups (10 rats each): Control group, ANP group and PDTC group. At the 6th h of the model, the changes of the serum amylase, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and pancreatic morphological damage were observed. The expressions of inducible nitric oxide (iNOS) were observed by SP immunohistochemistry. And the expressions of NF-kappaB p65 subunit mRNA were observed by hybridization in situ.
RESULTS
Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group ((7 170.40+/-1 308.63) U/L vs (4 074.10+/-1 719.78) U/L, P<0.05), ((76.95+/-9.04) micromol/L vs (65.18+/-9.02) micromol/L, P<0.05) respectively. MDA in both ANP and PDTC group rose significantly over that in control group ((9.88+/-1.52) nmol/L, (8.60+/-1.41) nmol/L, vs (6.04+/-1.78) nmol/L, P<0.05), while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control ((3 214.59+/-297.74) NU/mL, (3 260.62+/-229.44) NU/mL, vs (3 977.80+/-309.09) NU/mL, P<0.05), but there was no significant difference between them. Though they were still higher than those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-kappaB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group.
CONCLUSION
We conclude that correlation among NF-kappaB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.
目的
探讨核因子κB（NF-κB）激活在大鼠急性坏死性胰腺炎（ANP）中对活性氧的潜在作用，并评估吡咯烷二硫代氨基甲酸盐（PDTC，一种NF-κB抑制剂）的效果。
方法
通过逆行向胆胰管注射5%牛磺胆酸钠建立大鼠ANP模型。将大鼠随机分为三组（每组10只）：对照组、ANP组和PDTC组。在模型建立后6小时，观察血清淀粉酶、一氧化氮（NO）、丙二醛（MDA）、超氧化物歧化酶（SOD）的变化以及胰腺形态学损伤。采用SP免疫组化法观察诱导型一氧化氮合酶（iNOS）的表达。采用原位杂交法观察NF-κB p65亚基mRNA的表达。
结果
与给予PDTC的组相比，ANP组血清淀粉酶和NO水平显著降低（分别为(7170.40±1308.63)U/L对(4074.10±1719.78)U/L，P<0.05），((76.95±9.04)μmol/L对(65.18±9.02)μmol/L，P<0.05）。ANP组和PDTC组的MDA均显著高于对照组（(9.88±1.52)nmol/L，(8.60±1.41)nmol/L，对(6.04±1.78)nmol/L，P<0.05），但两组之间无显著差异。与对照组相比，ANP组和PDTC组的SOD水平均显著降低（(3214.59±297.74)NU/mL，(3260.62±229.44)NU/mL，对(3977.80±309.09)NU/mL，P<0.05），但两组之间无显著差异。虽然仍高于对照组，但PDTC组胰腺破坏较轻，与ANP组相比，PDTC组iNOS表达和NF-κB p65亚基mRNA表达较低。
结论
我们得出结论，NF-κB激活、血清淀粉酶、活性氧水平和组织损伤之间的相关性表明NF-κB在ANP发病机制中起关键作用。抑制NF-κB激活可能逆转大鼠ANP的胰腺损伤和活性氧的产生。
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