PGE_2对大鼠急性坏死性胰腺炎肾损伤的保护作用

Protective effect of PGE_2 on renal injury in rats with acute necrotizing pancreatitis

目的 :探讨前列腺素E2 (PGE2 )免疫干预对大鼠急性坏死性胰腺炎血清IL 10、TNF α、IL 1β水平及其对肾组织超微结构的影响。方法 :SD大鼠 91只随机分 4组 :假手术组 (n =7)、ANP组、PGE2 前、后干预组 (每组n =2 8) ,后三组随机分 1h、3h、6h、12h时段组 (n =7)。大鼠ANP模型用 5 %牛磺胆酸钠诱导 ,PGE2 前干预组在ANP模型制作前 2h肌肉注射 15 0 μg/kgPGE2 ,PGE2 后干预组在ANP模型完成时即刻肌肉注射 15 0 μg/kgPGE2 。分别采用ELISA检测各组各时段大鼠血清IL 10、TNF α、IL 1β含量并在电镜下观察ANP组、PGE2 前、后干预组 6h、12h时段肾组织细胞超微结构改变。结果 :PGE2 前或后干预组分别在模型制作后 1h和 3～ 12h时段IL 10含量增加 ,而相应时段的TNF α、IL 1β含量显著下降。PGE2 前干预6h和 12h时段 ,肾组织见凋亡小体 ;PGE2 后干预组 6h和 12h时段均未见肾小管上皮细胞坏死现象 ,炎症明显减轻 ,肾组织细胞结构明显改善。结论 :PGE2 前或后干预可以上调IL 10 ,下调TNF α、IL 1β,减轻急性坏死性胰腺炎肾组织的炎症反应 ,改善肾细胞的损害。

Objective:To explore the effect of prostaglandin E 2 (PGE 2) on interleukin-10(IL-10),tumor necrosis factor(TNF-α),interleukin-1β(IL-1β),and pathological changes of renal injury in rats with acute necrotizing pancreatitis (ANP).Methods:Ninety one SD rats were randomly divided into 4 groups:operation control group (n=7),ANP group,PGE 2 pre-intervention group (PGE 2-pre) and PGE 2 post-intervention group (n=28,respectively,).They were randomly subdivided into different time points for the latter three groups(1h,3h,6h,12h,n=7,respectively). ANP model of the rat induced by retrograde injection of 5% sodium taurocholate into the pancreatic duct.Every rat of PGE 2-pre group by intramuscularly injected 150μg/kg PGE 2 before 2 hours induction of ANP and PGE 2-post group administrated the same dose after ANP model immediately.The serum levels of IL-10,TNF-α and IL-1β activity were measured by ELISA at different time points in experimental rats and some of these kidney tissue were made ultrathin section and examined under electron microscopy (6h and 12h),respectively.Results:Serum levels of IL-10 were increased,but TNF-α and IL-1β levels were decreased of both groups treated with PGE 2 compared with control group (ANP) of different time points (P<0.001,respectivery).This result corelated well with ultrastructure findings,or renal injury interstitial swelling, injury of mitochondrion of renal tubular epithelial cell in ANP group,meanwhile,the kidney constitution lesion degress was significantly ameliorated in both groups of immuno-intervention with PGE 2.Conclusion:This study shows that either pre-intervention or post-intervention can enhance IL-10 levels,which potentially down-regulates TNF-α and IL-1β levels,relieves renal inflammation and improves renal injury in rats with acute necrotizing pancreatitis.