孟鲁司特对失血性休克复苏致急性肺损伤大鼠血清TNF-α、IL-6的影响及肺保护作用

Effects of montelukast on serum TNF-α and IL-6 levels in rats with hemorrhagic shock followed by resuscitation induced acute lung injury and lung protective effect

目的观察孟鲁司特对失血性休克复苏致急性肺损伤大鼠血清肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)的影响,探讨孟鲁司特的肺保护作用机制。方法选取健康成年大鼠24只,随机分为3组:假手术组(Sham组);失血性休克复苏致急性肺损伤模型组(HS组)和孟鲁司特治疗组(M组),每组8只。除Sham组外,其余2组动物制备失血性休克复苏急性肺损伤模型。M组大鼠在放血前30 min给予孟鲁司特7 mg/kg腹腔内注射,在再灌注之前以同样的剂量再注射1次。Sham组和HS组均给予等量的乙醇溶液腹腔内注射。计算肺组织湿干质量之比(W/D);采用酶联免疫吸附试验(ELISA)试剂盒定量测定血清TNF-α和IL-6含量;肺组织取样进行组织病理学检查。结果与Sham组比较,HS组肺组织W/D明显增大(P<0.05),血清TNF-α、IL-6水平明显升高(P均<0.05),肺组织病理改变为中度肺损伤。与HS组比较,M组肺组织W/D明显减小(P<0.05),血清TNF-α、IL-6水平明显降低(P均<0.05),肺组织病理改变明显减轻,为轻度肺损伤。结论孟鲁司特能够减轻失血性休克复苏大鼠血清TNF-α、IL-6水平的升高,从而减轻肺损伤,具有一定的肺保护作用。

Objective It is to investigate the effects of montelukast on serum TNF - α and IL - 6 levels in rats with hemor- rhagic shock followed by resuscitation induced acute lung injury and discuss montelukast lung protection mechanism. Methods Twenty-four normal rats were randomly divided into 3 groups（n = 8 each） ： sham operation group （sham group） , hemorrhagic shock followed by resuscitation group（ TIS group） , montelukast treatment group （M group）. Except the rats in sham group, rest rats were made into hemorrhagic shock followed by resuscitation models with lung injury. The rats in M group received a montelukast 7 mg/kg intraperitoneal injection 30 min before the induction of hemorrhagic shock, with the same dose repeated just before the reperfusion period. Both sham and HS group rats received the same volume of the ethanol carrier solution. The ratio of lung wet dry weight was calculated ; quantitative determination of serum TNF - α and IL - 6 was performed by enzyme- linked immunosorbent assay （ ELISA ） kit ; lung tissue sampling was gotten for histopathological examination. Results The lung tissue W/D obviously increased, the TNF-α and IL-6 serum levels were significantly highe, lung tissue pathology change for moderate lung injury in the HS group when compared with the sham group （P 〈 0.05 ）. The lung tissue W/D obviously decreased, the TNF - α and IL -6 serum levels were significantly lower, lung tissue pathology change for mild lung injury in the M group when compared with the HS group （ P 〈 0.05 ）. Conclusion Montelukast could significantly reduce the elevation of serum TNF -α and IL -6 levels in the hemorrhagic shocked rats, thus reduce the lung injury, which suggested that montelukast had a protective effect in haemorrhagic shock induced acute lung injury.