亚急性乐果染毒对自发性高血压大鼠心血管系统的影响

The Effects of 14-day Oral Exposure to Dimethoate on Cardiovascular Systems in Spontaneously Hypertensive Rats

[目的]观察14d乐果染毒对自发性高血压大鼠(SHR)心血管系统的影响,探讨钙离子稳态在该影响中的作用。[方法]雄性SHR,灌胃染毒,染毒剂量分别为0、12.5、25和50mg/kg,每天1次,连续14d。尾袖法测定大鼠血压,第15天处死动物,无机磷酸根法和RT-PCR检测酶活力和基因表达。[结果]25mg/kg以下乐果染毒大鼠血压升高,当剂量达到50mg/kg,大鼠血压没有显著升高的变化。染毒结束后,25mg/kg染毒组大鼠心肌Ca2+-ATPase活力显著升高,达到(2.32±0.33)μmolPi/(mg蛋白·h);50mg/kg组大鼠心肌Ca2+ATPase活力和Na+-K+-ATPase均显著升高,分别为(2.36±0.62)和(2.74±0.52)μmolPi/(mg蛋白·h)。Ca2+-ATPase基因表达随染毒剂量的增加而逐渐上调,剂量>25mg/kg时,表达值为(1.24±0.11),差异有显著性(P<0.05);50mg/kg乐果可诱导兰尼碱受体(RyR)的mRNA表达显著高于对照组(P<0.05),表达值分别为(1.49±0.27)和(0.96±0.16)。[结论]乐果引起自发性高血压大鼠血压的变化规律与接触剂量有关,一定剂量范围的可以升高。钙离子的代谢紊乱可能是乐果引起的心血管毒作用的机制之一。

[ Objective ] To observe the effects of dimethoate on cardiovascular systems of spontaneously hypertensive rats （ SHR ） after 14 days treatment and to explore the potential mechanisms. [ Methods ] Dimethoate at dose of 0, 12.5, 25 and 50 mg/kg was daily given with gavage to SHR for continuous 14 days. The blood pressure of rat tail was measured, and activities of enzymes, gene expression of Ca^2＋-ATPase and ryanodine receptors were determined. [ Results ] The blood pressure of SHR was increased at doses of 12.5 and 25 mg/kg and no change was observed at dose of 50 mg/kg during 14-day treatment. The activity of Ca^2＋-ATPase significantly increased at the dose of 25 mg/kg, and activities of Ca^2＋-ATPase and Na^＋-K^＋-ATPase significantly increased at the doses of 50 mg/kg. In the meantime, the gene expression of Ca^2＋-ATPase was significantly enhanced by dimethoate at dose of 25 mg/kg and 50 mg/kg, and the expression value were （ 1.24 ± 0.11 ） and （ 1.49±0.27 ）, respectively. Only in 50 mg/ kg dose group, the mRNA expression of ryanodine receptors was significantly higher than that in the control group （ P 〈 0.05 ）, and the expression value was（ 0.96 ± 0.16 ）. [ Conclusion ]Exposure to dimethoate at definite dose scope could raise the blood pressure of SHR. It was suggested that the disorder of calcium ion metabolism was involved in the cardiovascular toxicity induced by dimethoate.