腹膜透析对氧化乐果中毒兔多脏器的保护作用

Protective effects of peritoneal dialysis on multiple organs of rabbits with omethoate poisoning

目的探讨腹膜透析（peritoneal dialysis，PD）对急性有机磷农药中毒（acute organophosphorus pesticide poisoning，AOPP）多脏器损伤的保护作用及机制，为临床推广应用PD救治AOPP患者提供科学依据。方法选择健康口本大耳白兔18只，均为雄免，随机分为2组：对照组（n=9），PD组（n=9），两组均采用40％氧化乐果灌胃染毒，以出现瞳孔缩小、流涎、肌颤等为标准选择AOPP模型动物。两组动物均给以氯磷定及阿托品，PD组染毒后给予连续腹膜透析10次。动态观察两组动物血清肿瘤坏死因子-α及心肌酶、肝功、肾功及胰腺功能等生化指标测定的水平变化，同时应用Varian3900／Saturn2100T GC／MS仪对腹透液进行氧化乐果定性实验。所有数据均采用SPSS12．0软件包进行统计分析，两组之间比较采用t检验，与本组染毒前比较采用单因素方差分析后Dunnett-t检验，相关分析采用Pearson相关分析。结果染毒后两组动物血清TNF-α明显升高，肌酸激酶同工酶-MB、谷丙转氨酶、淀粉酶有明显改变，血肌酐改变不明显；PD组肿瘤坏死因子-α水平明显低于对照组，各项指标（肌酸激酶同工酶-MB、谷丙转氨酶、淀粉酶）也明显优于对照组；血清肿瘤坏死因子-α与肌酸激酶同工酶-MB、谷丙转氨酶、淀粉酶有明显的正相关关系，r分别为0．470、0．649、0．517；在腹透液中检测到氧化乐果。结论有机磷农药可通过多种机制导致心脏、肝脏、肾脏及胰腺损伤，炎症介质在AOPP致多脏器损伤的过程中发挥了重要作用；PD可以通过持续缓慢清除毒物及下调炎症介质发挥其对机体各脏器的保护作用。

Objective To explore the protective effects and the mechanisms of peritoneal dialysis （PD） on multiple organs induced by acute organophosphorus pesticide poisoning（ AOPP） in order to get a scientific basis for the application of PD to treat AOPP patients. Method The model of AOPP rabbits was made by intragastric administration of 25 mg/kg（0.5LD50）40% omethoate, and the symptoms of poisoning such as myosis, salivating and muscular tremor were abserved. Eighteen male Japanese rabbits were randondy divided into control group and peritoneal dialysis group （PD group）. Pralidoxime chloride and atropine were given by intra-muscular injection to rabbits of control group （ n = 9）. Rabbits of PD group （ n = 9） had a tube inserted into peritoneal cavity and peritoneal dialysis was given for 10 times after administration of pralidoxim chloride and atropine. Serum TNF-α, CK-MB （M. B. isoenzyme of creatine kinase）, ALT, creatinine, and amylase were observed dynamically. The dialysate of peritoneal dialysis was remained in the peritoneal cavity for testing the nature of intoxicant by using Varian 3900/ Saturn 2100T GC/MS device. All data were analyzed with SPSS version 12.0 software. Statistical comparison between two groups was carried out by using student t-test and analysis of variance（ANOVA） followed by Dunnett-t tests before and after intoxication. The pearson correlation analysis was used for determination of the relationship between TNF-α and other biomarkers. Results After intoxication, semmTNF-α, CK-MB, ALT and amylase increased except creatinine, but the serum levels of those biomarkers in PD group were significantly lower than those in control group. The level of TNF-α had positive correlations with CK-MB （ r = 0.470）, ALT （ r = 0. 649）, and amylase （ r = 0.517）. The omethoate was detected in the dialysate of peritoneal dialysis. Conclusions Organophosphorus pesticides can lead the cardiac muscle, liver, kidney and pancreas to the injury through several mechanisms, and the inflainmatory mediators play important role in the development of MODS induced by AOPP. Peritoneal dialysis can clean up intoxicants slowly and continuously and in turn lower down the level of inflammatory mediators resulted in protecting multiple organs from AOPP.