PPAR-γ激动剂对急性坏死性胰腺炎大鼠肺损伤的作用

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30 min股静脉注射10%DMSO(0.2 ml/100 g体重);罗格列酮组则注射等量10%DMSO溶解的罗格列酮(6 mg/kg体重).术后3 h、6 h、12 h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,12 h时分另0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12 h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 12 h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.

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

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 biliopancreatic 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 Resi 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-1mRNA 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-regnlating the expression of TNF-α and ICAM-1 mRNA.