VDR基因敲除鼠一氧化氮合酶和内皮素-1基因的表达

目的探讨维生素D受体(VDR)基因敲除鼠血压变化以及与血压水平密切相关的内皮型一氧化氮合酶、内皮素-1基因在主动脉的表达情况,了解维生素D、维生素D受体与血压的联系及可能机制。方法小鼠血压采用动脉血管插管法直接测定,主动脉内皮型一氧化氮合酶、内皮素-1基因表达采用实时定量聚合酶链式反应检测。结果内皮型一氧化氮合酶、内皮素-1基因均能在野生型正常鼠及维生素D受体基因敲除鼠主动脉表达。与野生型正常鼠比较,纯合子维生素D受体基因敲除鼠收缩压、舒张压明显升高,主动脉内皮型一氧化氮合酶基因表达明显下调,内皮素-1基因表达明显上调(P均<0.05),杂合子维生素D受体基因敲除鼠收缩压、舒张压及主动脉内皮型一氧化氮合酶、内皮素-1基因表达则无明显改变(P均>0.05)。相关性研究发现主动脉内皮型一氧化氮合酶基因表达水平与收缩压、舒张压水平呈负相关,与收缩压、舒张压水平呈正相关(P均<0.05)。结论纯合子维生素D受体基因敲除鼠存在与血压密切相关的主动脉内皮型一氧化氮合酶、内皮素-1基因表达水平明显异常。

Expression of endothelial nitri oxide synthase and endothelin-1 by genetic knocking.

Objective To investigate the changes of blood pressure, endothelial nitric oxide synthase(eNOS) and endothelin-l(ET-1) gene expression of aorta in vitamin D receptor(VDR) knockout mice. Methods eNOS, ET-1 gene expression of aorta were determined by real time polymerase chain reaction and blood pressure were measureed among 5 VDR(-/-) mice,5 VDR(+/-) mice and 5 wild-type[WT; or VDR(+/+)] mice. Results Expression of eNOS and ET-1 gene was detected in aorta of VDR knockout mice and wild-type mice.Compared with wild type mice, the values of systolic and diastolic pressure were higher, the levels of eNOS gene expression was significantly reduced,and the levels of ET-1 gene expression was significantly increased (P<0.05, respectively) in VDR(-/-) mice. When compared with VDR(+/-) mice and wild type mice, there were no significantly differentce differcnce in the values of systolic and diastolic pressure, the levels of eNOS and ET-1 gene expression (P>0.05, respectively), The level of eNOS gene expression was inversely associated with the values of systolic and diastolic pressure, The quantity of ET-1 gene express was positively correlated with the values of systolic and diastolic pressure(P<0.05, respectively). Conclusion There abnormalities in blood pressure, eNOS and ET-1 gene expression of aorta in VDR knockout mice were observed.