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目的研究盐酸戊乙奎醚联合阿托品对急性有机磷酸酯类农药中毒(Acute organic phosphorus pesticide poisoning,AOPP)所致肺损伤的疗效及可能的机制。方法 AOPP患者随机化分为阿托品治疗组,盐酸戊乙奎醚治疗组和盐酸戊乙奎醚联合阿托品治疗组,监测3组患者治疗前后呼吸频率、血气分析和临床症状的改变,并计算肺损伤评分;采用敌敌畏灌胃法建立AOPP大鼠模型,随机化分组并给予治疗后,苏木素-伊红(HE)染色观察大鼠肺组织病理改变,肺组织称重后计算肺系数,以全自动生化仪测定血清胆碱酯酶活性,并以ELISA法检测血清炎性细胞因子TNF-α、IL-6和肺组织匀浆中NF-κB活性。结果联合治疗组AOPP患者阿托品化时间、胆碱酯酶恢复时间、症状消失时间和住院时间均显著短于阿托品或盐酸戊乙奎醚治疗组患者(P<0.05);联合治疗组患者呼吸频率和血气变化也较治疗前明显改善,肺损伤评分也明显降低,且较两种单独治疗方案差异均有统计学意义(P<0.05);在AOPP模型大鼠中,联合治疗组大鼠肺间质充血、红细胞聚集等病理改变较模型组和阿托品或盐酸戊乙奎醚单独治疗组大鼠均明显减轻,联合治疗组大鼠血清及肺组织匀浆中胆碱酯酶活性分别升高至(319.29±18.57)U/L和(0.51±0.05)U/g,肺系数则降低至0.48±0.07,上述指标较阿托品或盐酸戊乙奎醚单独治疗组大鼠差异有统计学意义(P<0.05);血清炎性细胞因子水平和肺组织NF-κB活性监测结果也显示且较两种单独治疗时进一步显著降低(P<0.05)。结论阿托品与盐酸戊乙奎醚的适度联合应用可较为有效地缓解敏感个体AOPP所致的肺损伤,该作用可能与抑制NF-κB途径,减少致炎细胞因子TNF-α、IL-6的释放具有一定的关联,具体作用机制有待深入探讨。
Objective To study the efficacy and possible mechanism of penehyclidine hydrochloride combined with atropine on acute lung injury induced by Acute organic phosphorus pesticide poisoning (AOPP). Methods Patients with AOPP were randomly divided into atropine group, penehyclidine hydrochloride group and penehyclidine hydrochloride combined with atropine group. The changes of respiratory rate, blood gas analysis and clinical symptoms before and after treatment were monitored in 3 groups. The lung injury AOPP rat model was established by intragastric administration of Dichlorvos. The rats were randomly divided into groups and given the treatment. The pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining. The lung coefficients were calculated after lung tissue was weighed. Serum cholinesterase activity was measured. Serum inflammatory cytokines TNF-α, IL-6 and NF-κB in lung homogenates were detected by ELISA. Results AOPP, recovery time of cholinesterase, disappearance of symptoms and length of hospital stay in patients with AOPP in the combination therapy group were significantly shorter than those in the atropine or penehyclidine hydrochloride group (P <0.05). The respiratory rate, Blood gas changes significantly improved compared with before treatment, lung injury score was significantly lower than the two separate treatment programs were statistically significant (P <0.05); in the AOPP model rats, the combination therapy group rats lung interstitial Compared with the model group and atropine or penehyclidine hydrochloride alone group, the pathological changes of hyperoxia, erythrocyte aggregation and other pathological changes were significantly alleviated. The cholinesterase activity in serum and lung homogenate of the combination therapy group increased to (319.29 ± 18.57) U / L and (0.51 ± 0.05) U / g respectively, while the lung coefficient decreased to 0.48 ± 0.07. The above indexes were significantly different from those of atropine or penehyclidine hydrochloride alone group (P <0.05) Serum levels of inflammatory cytokines and NF-κB activity in lung tissue were also significantly decreased (P <0.05) compared with those of the two treatments alone. Conclusions A moderate combination of atropine and penehyclidine hydrochloride can effectively relieve lung injury induced by AOPP in sensitive individuals, which may be related to the inhibition of NF-κB pathway and the decrease of the release of inflammatory cytokines TNF-α and IL-6 Has a certain relationship, the specific mechanism needs further study.