慢性间断缺氧小鼠缺氧诱导因子1α的研究

目的　探索睡眠呼吸暂停综合征(SAS)的慢性间断性缺氧(CIH)对心血管损害的可能机制。方法　制作CIH小鼠模型。将30只ICR小鼠均分为实验组、空气模拟对照组及空白对照组。免疫组织化学方法检测实验小鼠心肌细胞缺氧诱导因子1α(HIF1α)及诱导型一氧化氮合成酶(NOS2)的表达。酶联免疫吸附测定(ELISA)方法检测小鼠血浆血管内皮生长因子(VEGF)及内皮素1(ET1)的浓度。结果　实验组心肌细胞HIF1α表达高于空白对照组(t=354,P<005)及空气模拟对照组(t=292,P<005);空白对照组HIF1α表达与空气模拟对照组比较差异无统计学意义(P>005)。实验组血浆VEGF浓度[(957±141)ng/ml]高于空白对照组[(810±062)ng/ml,q=427,P<005]及空气模拟对照组[(832±099)ng/ml,q=364,P<005];空白对照组血浆VEGF浓度与空气模拟对照组比较差异无统计学意义(P>005)。实验组血浆ET1浓度[(331±081)ng/ml]高于空白对照组[(250±072)ng/ml,q=364,P<005];空气模拟对照组血浆ET1浓度[(269±043)ng/ml]与实验组及空白对照组[(331±081)、(250±072)ng/ml]比较差异均无统计学意义(P均>005)。小鼠心肌细胞NOS2表达在各组间比较差异均无统计学意义(P均>005)。结论　CIH可引起小鼠HIF1α表达增加,并可促进HIF1α目的基因产物VEGF、ET1的表达。这可能

Effect of chronic intermittent hypoxia on hypoxia inducible factor-1α in mice

OBJECTIVE: To explore the mechanism of the effect of chronic intermittent hypoxia (CIH), an important pathophysiological state of sleep apnea syndrome (SAS), on cardiovascular system. METHODS: Thirty male ICR mice were divided into three groups: an experimental group, an air mimic control group and a blank control group. Immunohistochemistry was used to examine the expression of hypoxia inducible factor-1alpha (HIF-1alpha) and inducible nitric oxide synthase (NOS-2) in the myocardial cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma concentration of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1). RESULTS: The expression of HIF-1alpha in myocardial cells of the experimental group significantly increased compared with that of the air mimic control group (t = 3.54, P < 0.05), and that of the blank control group (t = 2.92, P < 0.05). The expression of HIF-1alpha in myocardial cells of the air mimic control group was not significantly different from that of the blank control group (P > 0.05). The plasma concentration of VEGF of the experimental group [(9.57 +/- 1.41) ng/ml] was significantly higher than that of the blank control group [(8.10 +/- 0.62) ng/ml, q = 4.27, P < 0.05], and that of the air mimic control group [(8.32 +/- 0.99) ng/ml, q = 3.64, P < 0.05]. While the plasma concentration of ET-1 of the experimental group [(3.31 +/- 0.81) ng/ml] was significantly higher than that of the blank control group [(2.50 +/- 0.72) ng/ml, q = 3.64, P < 0.05], it was not significantly different from that of the air mimic control group [(2.69 +/- 0.43) ng/ml, P > 0.05]. There was no significant difference between the expression of NOS-2 in myocardial cells of all groups (P > 0.05). CONCLUSION: CIH enhances the expression of HIF-1alpha and its target gene products VEGF and ET-1, and therefore affects the cardiovascular system.