还原型谷胱甘肽对脓毒症大鼠急性肺损伤的干预作用

Interventional effect of reduced glutathione on acute lung injury in septic rats

目的探讨还原型谷胱甘肽(GSH)对脓毒症大鼠急性肺损伤(ALI)的干预作用。方法将72只雄性Sprague-Dawley(SD)大鼠随机分为假手术组、模型组、干预组,每组各24只。干预组及模型组采用改良盲肠结扎穿孔法建立脓毒症ALI大鼠模型,假手术组建立假手术模型。术后30 min,干预组予腹腔内注射GSH 250 mg/kg,同时间模型组和假手术组予等量生理盐水。每组大鼠平均分为4个亚组,分别于术后6、12、24和48 h杀活取材。检测动脉血氧分压(PaO2)、血清C反应蛋白(CRP)、肺组织湿干重比(W/D)及肺组织丙二醛(MDA)、GSH浓度,并观察肺组织的病理改变。结果模型组PaO2及GSH含量明显低于假手术组和干预组(P均<0.05),且随时间延长而降低。模型组CRP水平、W/D及MDA含量均高于假手术组与干预组(P均<0.05),CRP值术后12 h时最高,而后逐步下降。另外,与模型组比,干预组病理切片所示肺损伤程度较轻。结论 GSH能抑制脓毒症ALI大鼠的炎症反应、减少氧化应激损伤,进而减轻ALI程度。

Objective To investigate the interventional effect of glutathione （GSH） on acute lung injury （ALl） in septic rats. Methods A total of 72 male SD rats were randomized into the sham-operated group, model group and intervention group, 24 rats in each group. Sepsis models were established through improved cecum ligation and perforation in the model and intervention groups, and the sham-operated model was established in the sham-operated group. Half an hour postoperatively, rats in the intervention group were inoculated with peritoneal injection of GSH, while the rats in the model and sham-operated groups injected with saline instead, all at a dose of 25 mg / 100 g. They were sacrificed at 6, 12, 24, 48 hours respectively and the specimens were taken at each point. Rats in each group were randomly divided into 4 equal subgroups. The arterial oxygen partial pressure （PaO2）, serum C-reactive protein （CRP）, the wet to dry weight ratio of lung （W / D）, the levels of malondialdehyde （MDA） and GSH were detected, and the pathological changes in lung tissue were also observed. Results The model group showed a significantly lower level in PaO2 and GSH compared with the other groups （all P 〈 0.05）, declined till 48 h. In the intervention group, the levels of serum CRP, W/D and MDA were remarkably higher than that in the model group （all P 〈 0.05）. The level of serum CRP reached the peak value at 12 h postoperatively, then gradually decreased. Remarkable pathological manifestations of pulmonary injury was observed in the model group, when compared with that in the intervention group. Conclusion GSH can inhibit inflammation, reduce the oxygen stress injury, thereby relieve ALI in rats with sepsis.