氢饱和生理盐水对小鼠重症急性胰腺炎及胰腺局部p38MAPK表达的影响

Effects of hydrogen - rich saline on severe acute pancreatitis and p38 mitogen - activated protein kinases in mice

目的观察氢饱和生理盐水（hydrogen—richsaline，HRS）对小鼠重症急性胰腺炎（severe acute pancreatitis，SAP）的作用，并探讨其对SAP小鼠胰腺局部p38丝裂原活化蛋白激酶（1,38MAPK）表达的影响。方法雄性C57BIM6小鼠180只，随机分为空白对照组、HRS对照组、SAP组和HRS组，腹腔注射雨蛙素和脂多糖诱导小鼠SAP模型，分别于造模后2、12、24和48h处死各组小鼠；HE染色观察胰腺组织病理学变化，从水肿、腺细胞坏死、炎症及出血等四项指标对胰腺损伤进行病理学评分；生化方法测定血清淀粉酶水平；ELISA法检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、IL-6和IL-10；qRT—PCR检测胰腺组织p38MAPK的mRNA表达量。结果HRS不影响SAP小鼠48h生存率；与同时间点SAP组比较，I-IRS组小鼠血清淀粉酶水平12h显著降低（P〈0．05），其余各时间点差异无统计学意义；HRS能减轻SAP小鼠胰腺病理变化，胰腺水肿、腺细胞坏死、炎症及出血评分均显著低于SAP组（P〈0．05）；与SAP组比较，HRS组血清IL-1β、TNF-α水平显著降低（P〈0．05），血清IL-6、IL-10差异无统计学意义；HRS组小鼠胰腺组织p38MAPKmRNA表达24h时间点显著低于SAP组（P〈0．05），其余各时点差异无统计学意义。结论HRS对SAP小鼠48h生存率无影响，能减轻SAP小鼠胰腺病理变化及炎症反应，可能与其下调胰腺局部p38MAPK表达有关。

Objective To investigate the protective role of hydrogen -rich saline （HRS） on severe acute pancreatitis （SAP） and impact of HRS on p38 mitogen - activated protein kinases （p38MAPK） in SAP mice. Methods One hundred and eighty male C57BL/6 mice were randomly divided into four groups ： normal control group, HRS control group, SAP group and HRS treatment group （HRS group）, SAP and HRS group were further divided into four （2, 12, 24, 48 h） subgroups （n = 20）. SAP mouse model was created by administering intraperitoneal injections of cerulein and lipopolysaccharide. Pancreatic injury was assessed by performing biochemical and histological assays and by measuring the inflammatory response of the pancreas, serum amylase, tumor necrosis factor - a （TNF -α）, interleukin （IL） -1β, IL- 6 and IL- 10 levels and histological morphometry were used to determine the severity of pancreatitis. Specifically, we examined changes in the expression of p38MAPK mRNA in pancreas. Results When SAP mouse models were treated with HRS, we found, through biochemical and histopathological analyses, that thepancreatic injury was significantly ameliorated.Administration of HRS to SAP mice led to decreased expression of pancreatic p38MAPK mRNA, and no alterations in the survival of mouse. Conclusions This study shows that HRS can alleviate the pancreas injury probably by inhibiting the inflammation response. In this way, p38MAPK may play a key role in the pathogenesis of inflammation response.