缺氧复合梭曼中毒大鼠心脏毒性效应的研究

Experimental studies of soman intoxication under hypoxia on the cholinergic system of rats' hearts

目的 探讨胆碱能系统在缺氧复合梭曼中毒心脏毒性效应增强机制中的作用 ,为提高在高原地区有机磷中毒的防治水平提供依据。方法 实验大鼠随机分为正常对照组、高原缺氧组、平原中毒组和缺氧中毒组。利用RT PCR技术检测心肌m2 受体mRNA的表达 ,Westernblot检测抑制性G蛋白含量 ,放射免疫法测定环磷酸腺苷 (cAMP)浓度及酶放射化学分析测定腺苷酸环化酶、蛋白激酶A活力。结果 与平原中毒组相比 ,缺氧条件下梭曼中毒 1 2、2 4h时m2受体表达增强了 1 7 9% (P <0 0 5)和 1 5 4% (P <0 0 5) ,抑制性G蛋白含量分别降低了 8 4% (P <0 0 5)和 7 5 % (P <0 0 5) ,cAMP浓度及腺苷酸环化酶 (AC)、蛋白激酶A(PKA)活力显著升高 (P <0 0 1 )。结论 复合损伤引起的m2 受体表达增强和cAMP PKA信号系统的异常升高 。

Objective To study the action of cholinergic signal transducting syst em on the mechanism of soman intoxication under high altitude hypoxia. Methods Experimental Wistar rats were randomly divided to four groups:normal control gro u p,high altitude hypoxia group, plain soman intoxication group and soman intoxica tion combined hypoxia group. The expression of m 2 receptor mRNA and the conce nt ration of inhibitory G protein α(Gi α) in rats myocardium were measured with R T PCR and Western bolt tec hinque, cAMP concentration was detected with Radioimmunoassay(RIA) and [γ 32 P] ATP was used to det ermined the activity of protein kinase A(PKA). Results Compared with plain soman intoxication group , the expression of m 2 receptor mRNA in soman intoxication combined hypoxia gr o ups increased 17 9% (P<0 05)and 15 4%(P<0 05) Gi α concentration de c reased 8 4% (P<0 05) and 7 5% (P<0 05) at 12 h and 24 h,and the con centration of cAMP and PK A activity increased markedly(P<0 01). Conclusion Effects of soman poisoning com bined with hypoxia on heart cholinergic signal transduction system were confirme d by m 2 receptor up regulated, Gi α expression suppress, cAMP formation and PKA acti vity increase. this enhancement maybe play an important role in the mechanism of heart injury induced by soman intoxication in the altitude.