PPAR-γ激动剂对急性坏死性胰腺炎大鼠肺损伤的作用

Effect of peroxisome proliferator-activated receptor-γ, ligand on acute necrotizing pancreatitis associated lung injury in rats

目的探讨过氧化物酶体增殖物激活受体γ（PPAR-γ）激动剂罗格列酮对ANP大鼠肺损伤的作用及其机制。方法雄性Wistar大鼠54只，按完全随机法分为假手术组（SO组）、ANP组、罗格列酮组。胆胰管逆行注射5％牛磺胆酸钠制备ANP模型。SO组、ANP组在造模前30min股静脉注射10％DMSO（0．2ml／100g体重）；罗格列酮组则注射等量10％DMSO溶解的罗格列酮（6mg／kg体重）。术后3h、6h、12h分批剖杀，每个时间点6只。检测血清淀粉酶、肺组织髓过氧化物酶（MPO）、肺湿干重比、支气管肺泡灌洗液（BALF）蛋白含量。取胰头部胰腺组织和肺组织行病理学检查。RT—PCR检测肺组织TNF-α mRNA和ICAM-1 mRNA的表达。结果ANP组血淀粉酶、肺MPO、湿干重比、BALF蛋白含量、胰腺及肺病理分值、肺脏TNF-α mRNA和ICAM-1 mRNA的表达水平均随时间延长而逐渐升高，12h时分别为（5353．0±728．2）U／L、（1．12±0．14）U／g、3．00±0．14、（0．438±0．056）g／L、11．17±0．93、8．17±0．75、0．57±0．03和1．53±0．08，均明显高于SO组（P〈0．05或P〈0．01）。罗格列酮12h组上述指标分别为（2847．4±841．0）U／L、（0．84±0．06）U／g、2．13±0．36、（0．283±0．078）g/L、7．75±0．27和4．33±0．82、0．26±0．04和0．84±0．02，均明显低于ANP 12h组（P〈0．05或P〈0．01），但仍高于SO组（P〈0．05或P〈0．01）。结论罗格列酮对ANP大鼠胰腺及肺损伤具有一定程度保护作用，其机制可能与抑制肺组织TNF-α、ICAM-1 mRNA的表达有关。

Objective To investigate the effect of Rosiglitazone on acute necrotizing pancreatitis （ANP） associated lung injury in rats and its potential mechanism. Methods Fifty-four male Wistar rats were randomly divided into sham operation group （SO group） , ANP group and Rosiglitazone pretreatment group （Rosi group）. ANP model was induced by retrograde infusion of 5% sodium taurocholate into the biliopanereatic duct. The rats of SO group, ANP group were injected with 10% dimethyl sulfoxide （DMSO） （0. 2 ml/100 g） via femoral vein 30 minutes prior to the operation. In Rosi group Rosiglitazone partes aequales （6 mg/kg） , which was dissolved in 10% DMSO, was injected. Rats were killed at 3 h, 6 h and 12 h after induction. The serum amylase, lung myeloperoxidase （MPO） , lung wet/dry （W/D） weight ratio, protein content of bronchoalveolar lavage fluids （BALF） were measured, and pancreas and lung pathologic changes were evaluated. RT-PCR was used for detecting the levels of TNF-α and ICAM-1 mRNA in lung tissue. Results In ANP group, the values a of serum amylase, MPO, W/D weight ratio, protein content of BALF, pancreas and lung pathologic score, lung TNF-α and ICAM-1 mRNA expression increased corresponding to the duration of ANP course, and the corresponding values at 12 h were （5353.0±728.2） U/L, （1.12 ±0.14） U/g, 3.00 ±0.14, 0. 438 ± 0. 056, 11.17±0.93 and 8.17 ±0.75, respectively, which were significantly higher than those in the SO group （P 〈0.05 or P 〈0.01 ）. The corresponding values in the Rosi group were （2847.4 ± 841 ） U/L, （0.84±0.06） U/g, 2.13±0.36, 0.283±0.078 g/L, 7.75±0.27, 4.33±0.82, 0.26±0.04 and 0.84±0.02, respectively, which were significantly higher than those in the SO group （P 〈 0.05 or P 〈 0.01 ）. Conclusions Rosiglitazone had protective effect on lung injuries in ANP rats through down-regulating the expression of TNF-α and ICAM-1 mRNA.