早期激素干预对急性一氧化碳中毒大鼠迟发性脑病的预防作用

Preventive effect of early hormonal intervention on delayed encephalopathy in rats with acute carbon monoxide poisoning

摘要:

目的 观察早期激素干预对急性一氧化碳中毒大鼠迟发性脑病（DEACMP）的预防作用。方法 将132只雄性Wistar大鼠随机分成3个实验组：CO中毒组（COP组）、CO中毒+地塞米松10 mg/kg组（DSMS-10组）和CO中毒+地塞米松30 mg/kg组（DSMS-30组），每组40只。另设健康对照组（NC组），12只。实验组按150 ml/kg腹腔内注射CO制备急性一氧化碳中毒动物模型，健康对照组大鼠注射等体积的空气。在中毒后30 min内DSMS-10组腹腔内注射地塞米松剂量为10 mg/kg/d，共7 d；DSMS-30组腹腔内注射地塞米松剂量为30 mg/kg/d，共7 d；NC组和COP组则注射等剂量生理盐水。监测中毒后90 min、7 d、14 d、21 d各组大鼠血清中髓鞘碱性蛋白（MBP）的含量，并在上述各时间点处死大鼠取脑组织，行HE及MBP免疫组化染色。采用Morris水迷宫实验评估动物的智力状态。结果 Morris水迷宫实验结果显示，COP组中有8只大鼠被判定为迟发性脑病；DSMS-10组中有6只被判定为迟发性脑病；而DSMS-30组和对照组未出现迟发性脑病。COP组大鼠血清中MBP含量增高最显著，DSMS-10组也有增高，DSMS-30组接近正常。差异在中毒后90 min、7 d最明显。病理学检查显示COP组中发生迟发性脑病的大鼠在中毒90 min~21 d后脑海马、皮质下出现神经元损伤、髓鞘碱性蛋白脱失等病理改变，上述病理改变在各实验组中均可观察到，但以COP组大鼠病变程度最重，DSMS-30组最轻。结论 10 mg/kg地塞米松可降低急性一氧化碳中毒大鼠迟发性脑病的发生率。30 mg/kg地塞米松则可避免迟发性脑病的发生。

Abstract:

Objective To observe the preventive effect of early hormonal intervention on delayed encephalopathy after acute carbon monoxide (CO) poisoning among rats.Methods A total of 132 male Wistar rats were randomly divided into three experimental groups: CO poisoning group (COP group), CO poisoning+dexamethasone (10 mg/kg) group (DSMS-10 group), and CO poisoning + dexamethasone (30 mg/kg) group (DSMS-30 group), n=40 for each, as well as one normal control group (NC group) (n=12). The rats in experimental groups were intraperitoneally injected with CO (150 ml/kg) to establish an animal model of acute CO poisoning, while the rats in NC group were injected with an equal volume of air. The DSMS-10 group received intraperitoneal injection of dexamethasone (10 mg/kg/d) for 7 days, and the DSMS-30 group received intraperitoneal injection of dexamethasone (30 mg/kg/d) for 7 days; the treatment began within 30 min after poisoning. The control group and COP groups were injected with an equal volume of saline. At 90 min, 7 days, 14 days, and 21 days after poisoning, serum myelin basic protein (MBP) levels were measured; rats were sacrificed to collect brain tissues for HE staining and MBP immunohistochemical staining. The Morris water maze test was used to evaluate the intelligence of rats.Results The Morris water maze test showed that 8 rats in the COP group were judged to have delayed encephalopathy, 6 rats in the DSMA-10 group were judged to have delayed encephalopathy, and no cases of delayed encephalopathy were found in the DSMS-30 group and NC group. The COP group showed the most significant increase in serum MBP level, the DSMS-10 group also showed increase in serum MBP level, and the DSMS-30 group had almost normal serum MBP level; the most significant differences were seen at 90 min and 7 days after poisoning. The pathological examination showed that the rats judged to have delayed encephalopathy in the COP group had neuronal damage and MBP depigmentation in the hippocampus and subcortical region at 90 min to 21 days after poisoning; these pathological changes could be observed in all experimental groups, severest in the COP group and mildest in the DSMS-30 group.Conclusions For the rats with acute CO poisoning, dexamethasone can reduce the incidence of delayed encephalopathy when given at 10 mg/kg and can prevent delayed encephalopathy when given at 30 mg/kg.