磷酸二酯酶4D基因与缺血性脑卒中的遗传易患性研究

Phosphodiesterase 4D gene and genetic susceptibility of ischemic stroke

目的探讨磷酸二酯酶4D(PDE4D)基因与缺血性脑卒中的关系。方法应用变性高效液相色谱技术筛查454例缺血性脑卒中患者和334例正常对照的PDE4D基因的单碱基多态性(SNP)45和SNP41,应用反相高效液相色谱技术检测人外周血PDE活性和SHR-SP大鼠、SD大鼠及低氧-窒息动物模型的外周血、大脑组织的PDE活性变化。结果本组人群中不存在文献报道的PDE4D基因的SNP45和SNP41的多态改变。病例组外周血PDE活性为13·8±3·1,显著高于对照组(7·3±2·3);SHR-SP的外周血和大脑组织的PDE活性低于正常对照SD大鼠;窒息组的外周血和大脑组织PDE活性稍高于正常对照组;低氧-窒息组的外周血和大脑组织PDE活性显著低于正常对照组和窒息组。结论PDE4D基因SNP45和SNP41与缺血性脑卒中无关,PDE参与了低氧应激过程。

Objective To investigate the relationship between phosphodiesterase （PDE） 4D gene and genetic susceptibility of ischemic stroke. Methods All 454 patients and 334 controls were recruited in our study, their single nucleotide polymorphism （SNP） 41 and SNP45 of PDFAD gene were detected by denaturing high performance liquid chromatography （ DHPLC ）. In addition, peripheral white blood cell＇ s PDE activities in some clinical samples, peripheral white blood cell and brain＇s PDE activities in 29 strokeprone spontaneously hypertensive rats （SHR-SP） and 40 SD rats （including hypoxemia-apneic animal models） were detected by reverse high performance liquid chromatography （RHPLC） method. Results There existed no SNP41 and SNP45 of PDFAD gene in the clinical samples, PDE activity of peripheral blood cell in ischemic stroke patients was 13.8 ± 3. 1, significantly higher than that in control group （7. 3 ±2. 3）. PDE activities in SHR-SP＇ s peripheral blood and brain were lower than those in normal SD rats; PDE activities of peripheral blood cell and brain in apnea group were slightly higher than those in normal SD rats, but PDE activities in hypoxia-apnea group were significantly lower than those in control and apnea group. Conclusions SNP45 and SNP41 of PDE4D gene do not associated with ischemic stroke, PDE takes part in the course of hypoxia-stress.