有机磷中毒家兔呼吸肌麻痹的病理机制和分子基础探讨

Molecular and pathological mechanism of respiratory muscular paralysis in rabbits poisoned with organophosphates

目的 探讨有机磷中毒家兔呼吸肌麻痹 (RMP)形成的分子基础和病理机制。方法 2 4只青紫蓝家兔分 4组 :敌百虫 (10LD ,1112 0mg kg)组 ,久效磷 (10LD ,2 2 2 4mg kg)组 ,甲基对硫磷(10LD ,74 10mg kg)组及正常对照组 ,每组 6只。家兔中毒经腹部皮下给药 ,中毒后 6h、 2 4h取血及肋间外肌 ,苏木精 伊红染色观察肋间外肌病理改变。用酶抑制法测肋间外肌组织匀浆中游离有机磷毒质(FOP)含量。用放射免疫法测血浆中肿瘤坏死因子α (TNF 浕) ,白细胞介素 1 β (IL 1β)及血栓素B2(TXB2 )含量。结果 中毒后 2 4h ,肋间外肌组织出现严重的病理损伤 ,可见肌纤维变性、坏死、横纹消失 ,肌原纤维崩解断裂。同时 ,肋间外肌组织匀浆中可检出不同浓度的FOP ,血浆中TNF 浕及ＴＸＢ2 含量显著高于正常 (TNF 浕 :T =2 5 ,P <0 0 0 5 ;TXB2 :T =2 1,P <0 0 0 5 )。结论 重度有机磷中毒可致动物呼吸肌出现严重的病理损伤 ,FOP和TXA2及TNF 浕在呼吸肌损伤中起重要作用 。

Objective To explore the molecular and pathological mechanism of respiratory muscular paralysis (RMP) in rabbits poisoned with organophosphates.Methods Twenty-four livid blue rabbits were divided into 4 groups:trichlorfon (10LD,1112.0 mg/kg),monocrotophos (10LD,22.24 mg/kg),methyl parathion (10LD,74.10 mg/kg) ,and control group,each with 6 rabbits.The organophosphates were administered with subcutaneous route.Samples of the external intercostal muscles and blood were collected at 6 h and 24 h after poisoning.Hematoxylin and eosin staining was carried out for pathological examination of the external intercostal muscles .The levels of free organophosphorus poisons (FOP S) in the muscle tissues were determined with enzyme inhibited method.The concentrations of tumor necrosis factor-alpha (TNF-ɑ),interleukin-1 beta (IL-1β),thromboxane B 2(TXB 2) in blood plasma were measured by radio - immunoassay technique.Results Severe pathological changes of the external intercostal muscles were observed at 24h after poisoning.The section showed degeneration and necrosis of those muscles,disappearance of cross striations and splitting of the myofibrils.It was also found there were different concentrations of FOPS of richlorfon,monocrotophos and methyl parathion in muscle tissues.TNF-ɑ and TXB 2 levels in blood plasma were significantly higher than those in control group (TNF-ɑ:T=25,P<0.005;TXB 2:T=21,P<0.005).Conclusion Serious organophosphorus pesticides poisoning can result in severe pathological injury of respiratory muscles.FOP S and TXA 2 and TNF-α play an important role in causing the injury.These changes may be important for the development of RMP.