胰高糖素样肽1对大鼠肺缺血再灌注损伤的影响

摘要

Objective To observe protective effects of Glucagon - like peptide - 1 against lung ischemia - reperfusion injury in rats and investigate its potential mechanism. Methods Single lung in situ ischemia - reperfusion animal model was used. 40 SD rats were randomly divided into four groups; sham - operation group(S group, n = 10) , ischemia - reperfusion group(I/R group, n = 10) , dipepti-dyl peptidaselV inhibitors group(VP group, n = 10) and Glucagon -like peptide -1 + dipeptidyl peptidaselV inhibitors group (G group, n = 10). The VP group underwent the same experiment procedure as I/R group in addition to valine pyrrolidide(20mg/kg) injected sub-cutaneously just before ligation 30min. In the G group, an intravenous infusion of GLP - 1 [4. 8pmol/( kg -min) ] continued throughout the procedure, besides the treatment of VP. Malondialdehyde (MDA) , superoxide dismutase (SOD) and xanthine oxidase (XO) in serum were measured. The lung tissue sampled was assayed for wet/dry weight ratio (W/D) , contents of myeloperoxidase( MPO) at the end of the experiment, and ultrastructural changes were observed under electron microscope. Results The results showed that XO and MDA increased and SOD decreased in serum in I/R group and VP group, while the same changes happened in G group but less severely(P < 0. 01). The value of W/D and MPO was much higher in I/R group and VP group, but decreased in G group( P < 0. 01). Electron microscope showed obvious ultrastructural injury brought by LIRI in I/R group and VP group, which was greatly attenuated in G group. Conclusion GLP - 1 may attenuate lung ischemia - reperfusion injury through dropping oxygen free radical level, decreasing lipid perox-idation and inhibiting of neutrophil aggregation.%目的 探讨胰高糖素样肽1(GLP-1)对大鼠肺常温缺血再灌注损伤的影响.方法 健康SD大鼠40只,随机分为假手术组(S组)、缺血再灌注组(IR组)、二肽基肽酶Ⅳ抑制剂组(VP组)和胰高糖素样肽1+二肽基肽酶Ⅳ抑制剂组(G组).复制在体肺缺血-再灌注损伤模型,VP组于缺血前30min皮下注射valine pyrrolidide (20mg/kg),G组予GLP-1 [(4.8pmol/(kg·min)]微量泵静脉输注,余步骤同VP组.实验结束时,自颈动脉抽血检测丙二醛(MDA)含量、超氧化物歧化酶(SOD)和黄嘌呤氧化酶(X0)活力;取肺组织测湿干重比(W/D),髓过氧化物酶(MPO)活力;电镜观察肺组织超微结构改变.结果 ①I/R组和VP组血清MDA、XO均显著高于S组(P均＜0.01),G组明显低于I/R组和VP组;②I/R组和VP组血清SOD均明显低于S组(P均＜0.01),G组显著高于I/R组和VP组(P＜0.01);③I/R组和VP组的W/D与MPO均高于S组(P＜0.01),G组显著低于I/R组和VP组(P＜0.01);④I/R组和VP组肺组织的超微结构损伤严重,G组损伤程度明显较轻.结论 GLP-l能够降低氧自由基水平,减轻脂质过氧化反应,抑制中性粒细胞聚集,减轻肺缺血-再灌注损伤.