脑梗死患者一氧化氮合酶基因多态性及其对一氧化氮的影响

Polymorphism of Nitric Oxide Synthase Gene and Nitric Oxide Production in Serum in Cerebral Infarction

目的观察脑梗死患者内皮型一氧化氮合酶(eNOS)基因多态性及一氧化氮(NO)变化情况。方法采用前瞻性病例对照研究,脑梗死组193例,均为发病2周内经头颅CT或MRI证实存在颈内动脉分布区梗死灶者,对照组103例为正常体检者。对两组eNOS基因4号内含子多态性进行测定,并采用Griess重氮化反应法和酶标法分别检测血清NO含量、NOS活性。结果脑梗死组eNOS基因4号内含子a等位基因(eNOS4a)携带者48例,对照组为12例,携带频率有显著性差异(χ2=8.86,P=0.003);经Logistic回归分析,eNOS4a携带是脑梗死的独立危险因素(P=0.032);脑梗死组NO产物浓度中位数为6.04(3.83～11.49)μmol/L,低于对照组6.89(4.64～12.43)μmol/L(P=0.022)。eNOS4a携带者NO产物浓度中位数为5.07(3.18～7.62)μmol/L,低于非携带者6.86(4.39～11.76)μmol/L(P=0.001)。脑梗死组NOS活性为(2.97±1.47)U/ml,对照组(3.16±1.46)U/ml,无显著性差异(P=0.517)。eNOS4a携带者NOS活性(2.77±1.13)U/ml,与非携带者(3.12±1.54)U/ml无显著性差异(P=0.100)。结论eNOS4a携带可能通过减少NO生成而在脑梗死发生过程中发挥作用。

Objective To observe the polymorphism of nitric oxide synthase（NOS）gene and the changes of nitric oxide（NO）in cerebral infarct.Methods The prospective case-control study was employed.Cases contained 193 subjects with cerebral infarction of internal carotid artery system within 2 weeks.Controls contained 103 subjects which came from the normal health checkup.The polymorphism in intron 4 of endothelial nitric oxide synthase（eNOS）gene were detected.NO content was measured by Griess diazotization assay and NOS activity by enzynatic assay.Results There were 48 subjects with allele a in intron 4 of eNOS gene（eNOS4a）in cases and 12 in controls.The frequencies of eNOS4a in cases was higher than that in controls（χ2=8.86,P=0.003）.Multivariate Logistic regression analysis confirmed that eNOS4a was an independent risk factors for cerebral infarction（P=0.032）.NO production and NOS activity were 6.04（3.83～11.49）μmol/L,（2.97±1.47）U/ml,respectively in cases,and 6.89（4.64～12.43）μmol/L,（3.16±1.46）U/ml,respectively in controls.NO production in cases were significantly lower than that in controls（P=0.022）.There was not differential in NOS activity between these two groups（P=0.517）.NO production and NOS activity were 5.07（3.18～7.62）μmol/L,（2.77±1.13）U/ml,respectively in the subjects with eNOS4a,and 6.89（4.64～12.43）μmol/L,（3.12±1.54））U/ml,respectively in the subjects without eNOS4a.NO production in the subjects with eNOS4a were significantly lower than that in the subjects without eNOS4a（P=0.001）.The NOS activities were not significantly different in subjects with or without eNOS4a（P=0.100）.Conclusion eNOS4a possibly exerted some effects on cerebral infarction by diminishing NO.