MS-302三道测量分析系统的应用及HI-6在离体膈神经-膈肌上抗梭曼的作用机制探讨

Application of MS-302 and effects of HI-6 on soman intoxication of isolated phrenic nerve diaphragm in rats

目的探讨抗神经毒化合物HI-6在离体膈神经-膈肌上抗梭曼的作用机制。方法采用MS-302三道测量分析系统,观察大鼠离体膈神经-膈肌的收缩功能,同时,测定膈肌乙酰胆碱酯酶(AChE)活性,观察药物对膈肌AChE活性的直接影响。结果(1)采用MS-302三道测量分析系统对膈神经-膈肌标本强直收缩曲线下的面积进行测量,较为直接地反映了膈神经-膈肌标本的生理功能,结果精确。(2)HI-6 10和100μmol/L对正常膈神经-膈肌收缩功能影响不明显,1 mmol/L对正常膈神经-膈肌收缩功能有抑制作用。HI-6 10μmol/L预防和治疗给药时,对梭曼抑制的标本收缩功能既没有保护作用也没有拮抗作用;100μmol/L给药有一定的保护和拮抗作用;剂量增加到1 mmol/L时,保护作用和拮抗作用都明显增强,且保护作用在30 min内最佳。(3)预先给予HI-6不能减弱梭曼对大鼠离体膈肌AChE的抑制,梭曼中毒后给予HI-6对梭曼抑制的膈肌AChE活性无显著影响。结论HI-6对梭曼抑制的离体膈神经-膈肌收缩功能的恢复可能是直接生理对抗作用,在本实验条件下未见膈肌酶活力有明显的恢复。

Objective To explore the mechanism underlying acetylcholinesterase （ACHE） reactivation and recovery by HI-6 against soman toxication in isolated phrenic nerve and diaphragm in rats. Methods MS-302 was used to determine the function of phrenic nerve-diaphragmatic muscle. AChE activity assay was operated to assess the reactivation of soman induced inhibition of AChE by HI-6. Results （1） MS-302 was a real time record system that acctdatedly determine the phrenic nerve-diaphragmatic muscle function. （2）HI-6 10 and 100 μmol/L had no effect on normal phrenic nerve-diaphragmatic muscle function,while HI-6 1 mmol/L had a positive inhibiting effect. When HI-6 10 μmol/L was administered preventively or therapeutically,no apparent protection was observed. While HI-6 100μmol/L appeared protective effect. And an apparently protective effect was observed in 30 min at HI-6 1 mmol/L. （3） HI-6 adminstered prevently or therapeutically had no reactivating effect on AChE of rat diaphragms inhibited by soman. Conclusion It demonstrated that the recovery ofphrenic diaphragm paralysis induced by soman is due to direct physiological antagonism of HI-6 instead of AChE reactivation.