Nrf2在甲基苯丙胺诱导大鼠肺小动脉重构和心肌损伤的表达

The expression of Nrf2 in pulmonary arteriole remodeling and myocardial injury induced by Methamphetamine in rats

目的研究甲基苯丙胺(MA)对大鼠肺小动脉和心肌组织的损伤作用以及Nrf2表达的变化。方法建立大鼠甲基苯丙胺慢性中毒模型,实验分为三组:对照组(control)、MA低剂量5mg/kg组(M5)和MA高剂量10mg/kg组(M10),分别用多导生理记录仪记录肺动脉压和体循环血压。将肺和心脏组织固定、包埋,切片进行HE染色,观察肺动脉和心肌形态学改变。计算肺动脉中膜厚度百分比。采用western blot方法检测肺动脉和右心室Nrf2蛋白表达的变化。结果与对照组相比,MA剂量依赖性地诱导肺小动脉重构和心肌细胞损伤,同时发现肺动脉和右心室Nrf2的核蛋白表达水平明显减少(<0.05)。结论 Nrf2抗氧化体系有可能参与甲基苯丙胺诱导大鼠肺小动脉重构和心肌损伤的发病机制。

Objective To study the expression and possible role of Nrf2 in pulmonary arteriole remodeling and myocardial injury induced by Methamphetamine（MA） in rats. Methods Models of chronic toxicity were established by injection of MA subcutaneously. Wistar rats were randomly divided into 3 groups： control group, M5 （MA,5mg/kg） group, and MAl0（MA,10mg/kg） group. The hemodynamic measurements were recorded by Polygraph System, morphological changes of the pulmonary arteries were obsmwed by HE staining, followed by measurement of the percentage of medial wall thickness. Nuclear Nrf2 expression in pulmonary arteries and right ventricles was detected by Western blotting. Results Compm＇ed with the control gronp, MA significantly induced the pulmonary arteriole remodeling and myocantial injury with dosedependent manner, inhibited the nuclear expression level of Nrf2 in the pulraonmy arteries and right ventricles（p〈0.05）. Conclusion Nrt2 antioxidant system may be involved in the pathogenesis of pulmonary vascular remodeling and myocardial injury in rats.