Pde4d和Alox5ap的mRNA水平与高血压性脑卒中和高血压病相关性的动物实验研究

目的使用与人类高血压性脑卒中近似的模型大鼠——易卒中型肾血管性高血压大鼠(stroke-prone renovascular hypertensive rats,RHRSP),在动物水平评价脑卒中易感基因Pde4d和Alox5ap mRNA水平的变化规律与高血压性脑卒中和高血压病的相关性。方法建立血压正常组,梯度高血压Ⅰ、Ⅱ和Ⅲ组(其收缩压分别为140～159mmHg、160～179mmHg和180～199mmHg)和自发卒中组,分别提取大鼠外周血的总RNA,逆转录后进行荧光实时定量PCR。结果自发卒中组Pde4d和Alox5ap的mRNA表达水平明显高于其他组。Pde4d在梯度高血压Ⅰ组的表达量稍高于血压正常组、梯度高血压Ⅱ、Ⅲ组;Alox5ap在血压正常组和梯度高血压组的表达量差异无统计学意义。结论动物实验表明Pde4d与Alox5ap基因过表达均与高血压性脑卒中存在相关性,Pde4d在梯度高血压Ⅰ组表达稍高可能与大鼠机体应激相关;两基因与高血压病本身无显著相关性,是脑卒中的独立危险因素;两基因的过表达可能通过参与动脉壁的炎症反应而介导脑卒中的发生。

Association between mRNA level of Pde4d and Alox5ap and hypertensive stroke as well as hypertension in rats

OBJECTIVE: To evaluate whether mRNA levels of Pde4d and Alox5ap were associated with hypertensive stroke and hypertension in stroke-prone renovascular hypertensive rats (RHRSP) which could simulate human being's hypertensive cerebral stroke. METHODS: Five groups were established: normotensive group, gradient hypertensive groups I, II and III(with contractive pressure of 140-159 mmHg, 160-179 mmHg and 180-199 mmHg respectively) and spontaneous stroke group. RNA from leukocytes in peripheral blood of each rat underwent real time PCR after reversed. RESULTS: The mRNA levels of Pde4d and Alox5ap of spontaneous stroke group were statistically higher than that of the other groups. Expression of Pde4d of hypertensive group I was a bit higher than that of normotensive group and hypertensive groups II and III; as for Alox5ap, there was no statistical difference between normotensive group and all gradient hypertensive groups. CONCLUSION: Animal experiments come to conclusions that over-expression of Pde4d and Alox5ap are associated with hypertensive stroke but not with hypertension. Therefore, the two genes confer the risk of hypertensive stroke independent of traditional risk factors. It is speculated that over-expression of Pde4d and Alox5ap can motivate onset of hypertensive cerebral stroke by participating in inflammation of arterial walls.