内质网及硝化应激在肥胖大鼠胰腺炎中的作用

The role of endoplasmic reticulum stress and nitrative stress in obese rats with acute pancreatitis

目的观察内质网应激（ERS）和硝化应激（NS）在肥胖大鼠急性胰腺炎中的作用。方法SD大鼠随机分为对照组（NC）、单纯胰腺炎组（AP）和肥胖胰腺炎组（OB＋AP）。检测各组血清淀粉酶、脂肪酶含量；同时行胰腺、肺组织苏木素-伊红（HE）染色；Western blot检测各组胰腺组织的ERS标志物[肌醇需求激酶-1α（IRE-1α）、葡萄糖调节蛋白-78（GRP-78）、CCAAT增强子结合蛋白（CHOP）]和NS标志物[诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS）]的表达。结果与AP组比较，OB＋AP组血清淀粉酶、脂肪酶水平明显升高；与AP组相比，OB＋AP组胰腺的水肿、炎性细胞浸润更明显，肺出血和肺泡上皮增生更严重；与AP组相比，OB＋AP组内质网应激标记物IRE-1α[（0．65±0．03）比（0．46±.0．04）]、GRP-78[（0．85±0．03）比（0．43±0．03）]、CHOP[（0．62±0．03）比（0．41±.0．02）]和硝化应激标记物iNOS[（1．01±0．10）比（0．36±0．04）]表达升高（P〈0．05），而eNOS[（0．36±.0．05）比（0．69±.0．04）]表达降低（P〈0．05）；免疫组织化学染色显示3-硝基酪氨酸在AP组和OB＋AP组均表达，而在NC组无表达。结论对SD大鼠而言，肥胖可以通过增加ERS和NS的程度而加重胰腺炎。

Objective To investigate the role of endoplasmic reticulum stress and nitrative stress in obese rats with acute pancreatitis. Methods SD rats were randomly divided into normal control group （NC）, acute pancreatitis group （AP） and obesity ＋ acute pancreatitis group （OB ＋ AP）7 We evaluated the severity of AP biochemicaUy and morphologically. The expression of inositol requiring enzyme -1α（IRE -1α）, glucoseregulated protein （GRP） -78, CCAAT enhancer binding protein（CHOP） , induc, ible nitric oxide synthase （iNOS） and end,,thelial nitric oxide synthase （eNOS） was assayed by Western blotting. Results Compared with AP group, serum amylase and lipase levels were significantly higher in OB ＋ AP group. Compared with AP group, the edema and inflammatory cell infiltration of pancreas were more obvious, and the pulmonary hemorrhage and alveolar epithelial hyperplasia were more severe in OB ＋ AP group. Compared with AP group, the expression of endoplasmic reticulum stress markers IRE- 1α[（0.65 ±0.03） vs. （0.46 ±0.04）], GRP-78 [（0.85 ±0.03） vs. （0.43 ±0.03）], CHOP [ （0. 62 ＋ 0.03 ） vs. （0.41 ± 0. 02 ） ] and nitrosative stress marker iNOS [ （ 1. 01 ± 0. 10 ） vs. （0. 36 ± 0. 04） ] was higher in OB ＋ AP group （ P 〈 0. 05 ）, while the expression of eNOS [ （ 0. 36 ± 0. 03 ） vs. （0.69 ± 0.04） ± was decreased （ P 〈 0.05 ）. Immunohistochemistry showed that 3 - nitrotyrosine was - pressed in both AP and OB ＋ AP group, but not in NC group. Conclusion Ror SD rats, obesity can aggravate panereatitis by inereasing the degree of endoplasmie retieulum stress and nitrative stress.