糖皮质激素或抗菌药物联合治疗脓毒症大鼠的疗效与血清喹啉酸水平的相关性

Relationship between therapeutic effect of glucocorticoids or combination of antibacterial drugs on sepsis in rats and serum level of quinolinic acid

目的探讨糖皮质激素(地塞米松)或抗菌药物联合治疗(阿莫西林+庆大霉素+甲硝唑)脓毒症大鼠的疗效与血清喹啉酸(Quinolinic acid,QUIN)水平的相关性。方法采用盲肠结扎穿孔法复制大鼠脓毒症模型,分别给予地塞米松和抗菌药物(阿莫西林+庆大霉素+甲硝唑)联合治疗,并设假手术组。分别于术后4、12、36、72和144 h记录大鼠死亡情况,并计算存活率;进行白细胞及分类计数;采用气质联用法检测血清QUIN水平。结果模型组大鼠术后4 h开始血中白细胞总数及中性粒细胞比例明显升高,12 h达峰值并出现动物死亡;血清中QUIN水平术后12 h开始明显升高,72 h达峰值并持续保持高水平。抗菌药物联合治疗可显著降低大鼠的死亡率、血中白细胞总数及中性粒细胞比例,显著抑制血清中QUIN水平的升高。地塞米松单用无明显降低脓毒症大鼠死亡率的作用,但可显著降低血中白细胞总数和QUIN水平,而升高中性粒细胞比例。结论血清QUIN水平与脓毒症的炎症进程密切相关,其变化可能是预测脓毒症转归的有效指标之一。

Objective To investigate the relationship between therapeutic effect of dexamethasone or combination of an- tibacterial drugs （amoxicillin, gentamicin and metronidazole） on sepsis in rats and the serum level of quinolinic acid （QUIN）. Methods Rat model of sepsis was copied by cecum ligation and puncture. The model rats were treated by dexamethasone and combination of antibacterial drugs （amoxicillin ＋ gentamicin ＋ metronidazole） respectively, using those receiving sham operation as control The deaths of rats were recorded 4, 12, 36, 72 and 144 h after operation, based on which the survival rate was calculated. The total white blood cells （WBCs） and neutrophils were counted, and the serum QUIN level was determined by gas chromatography-mass spectrometry. Results Both the WBC count and per- centage of neutrophils in model rats increased significantly 4 h and reached a peak value 12 h after operation when deaths appeared. However, the serum QUIN level increased significantly 12 h and reached a peak value 72 h after oper- ation, while maintained at a high level afterwards. The combination of antibacterial drugs decreased the death rate, WBC count and percentage of neutrophils significantly, and inhibited the increase of serum QUIN level significantly. However, the death rate of rats treated with dexamethasone alone showed no significant decrease, while the WBC count and QUIN level decreased significantly, and the percentage of neutrophils increased. Conclusion Serum QUIN level was closely related to the inflammatory progress of sepsis, which might be used as an effective index for prediction of prognosis of the disease.