肾上腺髓质素对腹腔感染所致肺损伤大鼠肺组织中PPAR-γ的影响

Effect of Adrenomedullin on PPAR-γ Protein Expression in Lungs of Rats with Intra-abdominal Infection

目的探讨肾上腺髓质素(ADM)对腹腔感染所致急性肺损伤(ALI)大鼠肺组织中过氧化物酶体增殖物激活受体γ(PPAR-γ)蛋白表达的影响。方法采用盲肠结扎穿孔(CLP)制作大鼠腹腔感染模型,随机分为假手术组(Sham)、Sham+ADM组,CLP组和CLP+ADM治疗组。持续监测各组大鼠颈动脉压力。分别于手术后6h、18h测定支气管肺泡灌洗液(BALF)中白细胞计数及肿瘤坏死因子α(TNF-α)含量;肺组织HE染色及肺损伤组织学评分;测定肺组织湿/干重比值(W/D);用Westernblot法观察肺组织中PPAR-γ蛋白表达变化。结果各组之间平均动脉压在各时段差异无统计学意义(P>0.05)。CLP组6h、18h时的肺损伤组织学评分(P<0.05)以及BALF中白细胞数(P<0.05)、肿瘤坏死因子α(TNF-α)含量均明显高于Sham组和CLP+ADM组(P<0.05)。CLP组在18h的W/D值较Sham组和CLP+ADM有明显升高(P<0.05),而CLP+ADM组18h的W/D值低于CLP组(P<0.05)。CLP组6h、18h大鼠肺组织中PPAR-γ蛋白表达较Sham组和CLP+ADM均有显著下降(P<0.05)。结论肾上腺髓质素可以减轻腹腔感染大鼠的肺损伤程度,并且上调肺损伤大鼠肺组织中PPAR-r蛋白的表达。

Objective To investigate the effect of adrenomedullin （ADM） on PPAR-γ protein expression in lungs of rats with intra-abdominal infection. Methods The rat model of sepsis was established by cecal ligation and puncture （CLP）. Forty Wistar rats weighting 220 to 250 g were randomly assigned to 4 groups：Sham group,Sham＋ADM group,CLP group,and CLP＋ADM group. The rats were killed 6 or 18 hours after the operation,respectively. The mean arterial blood pressure （MABP） was monitored. The lung tissues were stained with hematoxylin and eosin,and the lung-injury score was calculated. Lung wet/dry weight ratio （W/D） was measured. Bronchoalveolar lavage fluid （BALF） was collected to determine the number of neutrophils and the concentration of tumor necrosis factor-α （TNF-α）. PPAR-γ protein expression in lung tissues was detected by Western blot. Results There was no significant difference in MABP between any 2 groups. Compared with Sham and CLP＋ADM groups,the number of neutrophils and the concentration of TNF-α in BALF and the lung-injury score significantly increased in CLP group after 6 and 18 hours （P〈 0.05）. The lung W/D significantly increased in CLP group after 18 hours （P〈 0.05）. The expression of PPAR-γ protein in CLP group was lower than that in Sham and CLP＋ADM groups after 6 and 18 hours （P〈 0.05）. Conclusion ADM could alleviate acute lung injury in rats with intra-abdominal infection by up-regulating the expression of PPAR-γ protein in lung tissue.