睡眠呼吸暂停综合征血管内皮功能障碍的机制探讨

发布时间：2018-05-29 21:25

本文选题：慢性间歇低氧 + 血管内皮　；参考：《苏州大学》2010年硕士论文

【摘要】： 第一部分慢性间歇低氧小鼠血管内皮功能障碍及相关机制的探讨目的探讨慢性间歇低氧(CIH)对小鼠血管内皮功能的影响。方法在我们前期研究已建立的间歇低氧小鼠模型基础上,采用硝酸还原酶法检测间歇低氧(CIH)1周、2周、3周、4周、6周后小鼠血清NO的水平,并应用化学比色法测定小鼠血清eNOS的活性,观察低氧不同时间段NO体系的变化情况,并用透射电镜观察低氧6周小鼠肺动脉内皮细胞结构的变化。结果(1)在间歇低氧造模第1周时,CIH组小鼠血清NO水平较对照组有所下降,但差异无统计学意义(p0.05);自低氧第2周始,小鼠血清NO下降水平较UC组比较差异有统计学意义,(CIH 78.96±9.93μmol/L UC 106.31±19.06μmol/L,p0.05)。随着间歇低氧时间的延长,CIH组小鼠血清NO水平呈逐渐下降趋势,各造模时间段两组之间比较,差异均有统计学意义(p0.05或p0.01)。另外,CIH各组小鼠血清eNOS活性也随造模时间呈逐渐下降趋势,自间歇低氧1周始,CIH组血清eNOS活性较对照组有所下降,差异有统计学意义(CIH 22.26±2.96 UC 25.58±3.47 U/ml,p0.05);随后低氧各组小鼠血清eNOS活性均较UC组显著下降,两组间比较差异均有统计学意义(p0.05或p0.01)。 (2)低氧第6周后小鼠肺动脉内皮超微结构的改变:电镜下观察发现,间歇低氧小鼠肺动脉内皮细胞核膜模糊,染色质边集,内膜向管腔内突起,并可见内皮细胞水肿,线粒体嵴稀疏,轻度肿胀,部分呈空泡变性。结论随着间歇低氧时间的延长,小鼠血清NO水平和eNOS活性逐渐下降,肺动脉内皮结构受损。第二部分阻塞性睡眠呼吸暂停低通气综合征患者血清NO水平的检测及其临床意义目的探讨不同程度阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者血清NO水平的变化的意义。方法纳入2008年6月-2009年2月在我院睡眠中心就诊的73名男性成年打鼾患者,进行多导睡眠图(PSG)监测。按照OSAHS诊断标准,根据呼吸紊乱指数(AHI)将所有对象分为3组:单纯鼾症组(AHI5/h,12例),轻-中度(AHI 5-40/h,36例)和重度OSAHS组(AHI40/h,25例),采用硝酸还原酶法测定其血清NO水平,比较血清NO水平、高血压发生率、体重指数(BMI)和PSG监测的睡眠呼吸参数(最低氧饱和度(L-SaO2)、SaO290%的时间(min)、平均氧饱和度(M-SaO2)以及AHI)在不同严重程度的OSAHS患者间的差异,同时分析血清NO水平和各参数之间的相关性。结果各组研究对象的年龄、BMI之间的差异无统计学意义(p0.05)。随着OSAHS严重程度加重,高血压发生率逐步上升;重度OSAHS组氧减指标较其他两组加重,差异有显著统计学意义(均p0.01),血清NO水平随着OSAHS严重程度逐渐降低,组间比较有显著统计学意义(p0.01),OSAHS患者的血清NO水平与AHI、SaO290%的时间呈负相关(r分别为-0.83,-0.54,p0.01),与M-SaO2、L-SaO2呈正相关(r分别为0.48和0.52,均p0.01)。结论阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者高血压发生率随着OSAHS的严重程度而升高,OSAHS患者血清NO水平随病情严重程度的加重而降低,这可能是高血压病发生、发展的重要因素之一。
[Abstract]:Part 1: endothelial dysfunction and related mechanisms in chronic intermittent hypoxia mice
Objective to investigate the effects of chronic intermittent hypoxia (CIH) on vascular endothelial function in mice.
Methods on the basis of our pre established intermittent hypoxia mice model, the serum levels of NO in mice were measured by the nitrate reductase method for 1 weeks, 2 weeks, 3 weeks, 4 weeks and 6 weeks, and the activity of eNOS in the serum of mice was measured by chemical colorimetry, and the changes of NO system in different periods of hypoxia were observed and the transmission electron microscope was used. The changes of pulmonary artery endothelial cell structure in 6 week hypoxia were observed.
Results (1) at first weeks of intermittent hypoxia, the serum level of NO in CIH group was lower than that of the control group, but the difference was not statistically significant (P0.05). Since the second weeks of hypoxia, the decrease of serum NO in mice was statistically significant compared with that of the UC group (CIH 78.96 + 9.93 mu mol/L UC 106.31 + 19.06 mol/L, P0.05). The level of serum NO in the CIH group was gradually decreasing. The difference between the two groups was statistically significant (P0.05 or P0.01). In addition, the serum eNOS activity of all CIH mice decreased gradually with the time of modeling, and the activity of eNOS in the CIH group decreased from 1 weeks to the intermittent hypoxia, and the difference was statistically significant. Significance (CIH 22.26 + 2.96 UC 25.58 + 3.47 U/ml, P0.05), and then the serum eNOS activity of the mice in each group was significantly lower than that in the UC group, and the difference was statistically significant between the two groups (P0.05 or P0.01).
(2) ultrastructural changes in the pulmonary artery endothelium of mice after sixth weeks of hypoxia: under the electron microscope, it was found that the nuclear membrane of the pulmonary artery endothelial cells in the intermittent hypoxic mice was blurred, the chromatin was set, the endometrium protruded into the lumen, the edema of the endothelial cells, the sparsity of the crista, the slight swelling of the mitochondria, and some vacuolated degeneration.
Conclusion with the prolongation of intermittent hypoxia time, serum NO level and eNOS activity in mice gradually decrease, and the structure of pulmonary artery endothelium is impaired.
The second part of serum NO level in patients with obstructive sleep apnea hypopnea syndrome and its clinical significance
Objective to explore the significance of changes of serum NO levels in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).
Methods the polysomnography (PSG) was carried out in 73 male adult snoring patients in the sleep center of our hospital in February -2009 June 2008. According to the OSAHS diagnostic criteria, all the objects were divided into 3 groups: simple snoring group (AHI5/h, 12 cases), mild to moderate (AHI 5-40/h, 36 cases) and severe OSAHS group (AHI40/h, 25 cases). The serum level of NO was measured with nitrate reductase, and the difference in the serum NO level, the incidence of hypertension, the body mass index (BMI) and PSG monitoring of the sleep breathing parameters (L-SaO2), the time of SaO290% (min), the average oxygen saturation (M-SaO2) and AHI) in the OSAHS patients with different severity, and the analysis of the serum NO level were compared. Correlation with each parameter.
Results there was no significant difference in age and BMI between the subjects of each group (P0.05). As the severity of OSAHS aggravated, the incidence of hypertension increased gradually, and the oxygen reduction index in the severe OSAHS group was heavier than the other two groups, and the difference was statistically significant (P0.01). The serum NO level gradually decreased with the severity of OSAHS, and there was a significant difference between the groups. Statistical significance (P0.01), the level of serum NO in OSAHS patients was negatively correlated with the time of AHI, SaO290% (R respectively -0.83, -0.54, P0.01), and was positively correlated with M-SaO2, L-SaO2 (r was 0.48 and 0.52 respectively).
Conclusion the incidence of hypertension in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) increases with the severity of OSAHS, and the level of serum NO in OSAHS patients decreases with the severity of the disease, which may be one of the important factors for the development of hypertension.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R766

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