睡眠呼吸暂停模式慢性间歇低氧致大鼠心肌细胞凋亡及纤维化的实验研究

发布时间：2018-03-08 22:11

本文选题：睡眠呼吸暂停　切入点：慢性间歇低氧　出处：《东南大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景睡眠呼吸暂停的患者夜间呈现反复的低氧血症、高碳酸血症和睡眠结构紊乱,而反复的间歇性缺氧所引起的低氧对心血管系统造成了严重的损害,大量的动物实验及临床观察表明睡眠呼吸暂停综合症会导致高血压,慢性间歇缺氧、化学感受器的刺激,交感神经和肾素-血管紧张素系统的激活,可能促进心肌细胞凋亡及心肌纤维化,进而使心血管疾病加重。然而对于睡眠呼吸暂停模式慢性间歇低氧是如何对心肌细胞的凋亡及心肌纤维化产生影响不可知。目的睡眠呼吸暂停模式慢性间歇低氧致大鼠心肌细胞凋亡及纤维化的实验研究。方法 (1)将大鼠随机分为慢性间歇性低氧组(CIH组)和对照组(NC组)：慢性间歇性低氧组大鼠(CIH组)每天9：00am-5:00pm置于慢性间歇性低氧舱内8小时,NC组大鼠在与CIH组相同的饲养舱但为正常氧浓度环境饲养。 (2)饲养35天结束时,超声心动图检查测定左心室舒张末期内径(LVlDd)、左心室收缩末期内径(LVlDs)、左心室短轴缩短率(LVFS)和左心室射血分数(LVEF)。(3)取心肌组织分别行HE染色,TUNEL染色,苦味酸-天狼星红染色检测心肌结构、心肌凋亡、心肌纤维化水平的变化。(4)提取蛋白进行Western blot检测心肌细胞HIF-1 α蛋白表达水平。(5)采用Spss 13.0进行数据资料分析。P0.05认为具有统计学显著差异。结果 (1)与NC组相比,CIH组中LVIDs水平明显升高[4.094±1.131mm(CIH)与3.060±0.923mm(NC),p0.01],而LVEF[74.247±10.345%(CIH)与87.290±9.436%(NC),p0.01]和LVFS[38.127±11.564%(CIH)与51.170±12.425%(NC),p0.01]均低于NC组。 (2)HE染色提示CIH组大鼠心肌结构受损,细胞水肿,部分细胞坏死,TUNEL染色提示CIH组的凋亡细胞增多,苦味酸-天狼星红染色提示CIH组大鼠纤维化水平增加。 (3)CIH组较NC组比较,通过Western Blot测得HIF-1α水平升高[0.62±2.89E-0.5(CIH)与0.45±0.01(NC),P0.05]。结论 (1)睡眠呼吸暂停模式慢性间歇低氧影响了大鼠心功能,使大鼠心功能降低； (2)睡眠呼吸暂停模式慢性间歇低氧加重了大鼠的心肌损伤及心肌纤维化； (3)睡眠呼吸暂停模式慢性间歇低氧激活大鼠缺氧诱导因子1 α的表达。
[Abstract]:Background patients with sleep apnea present recurrent hypoxemia, hypercapnia and sleep structure disorder at night, and hypoxia caused by repeated intermittent hypoxia causes severe damage to the cardiovascular system. Numerous animal experiments and clinical observations have shown that sleep apnea syndrome can lead to hypertension, chronic intermittent hypoxia, chemosensory stimulation, sympathetic and renin-angiotensin system activation. May promote cardiomyocyte apoptosis and myocardial fibrosis, However, the effect of chronic intermittent hypoxia on cardiomyocyte apoptosis and myocardial fibrosis in sleep apnea pattern is unknown. Objective chronic intermittent hypopnea in sleep apnea pattern. Experimental study on cardiomyocyte apoptosis and fibrosis in rats induced by oxygen. Methods: rats were randomly divided into chronic intermittent hypoxia group (CIH group) and control group (NC group: chronic intermittent hypoxia group (CIH group)). At the end of 35 days, the rats in the 8-hour hypoxia group were fed in the same feeding chamber as the CIH group but in the normal oxygen concentration environment. Left ventricular end-diastolic diameter (LVlDdN), left ventricular end-systolic diameter (LVlDsN), left ventricular short-axis shortening rate (LVFS) and left ventricular ejection fraction (LVEFN) were measured by echocardiography. Myocardial structure and myocardial apoptosis were detected by picric acid-Sirius red staining. The expression of HIF-1 伪 protein in cardiomyocytes was detected by Western blot. The expression of HIF-1 伪 protein was detected by Spss 13.0. P05 showed that there was a significant difference in the expression of HIF-1 伪 protein. Results: compared with the NC group, the expression of HIF-1 伪 protein was significantly different from that of the NC group. The levels of LVIDs in the middle group [4.094 卤1.131 mm] and 3.060 卤0.923 mm / h were significantly higher than those in the NC group, while the levels of LVEF [74.247 卤10.345 mm] and LVFS [87.290 卤9.436%] and LVFS [38.127 卤11.5641CIH] and 51.170 卤12.425mm / ncccncncncncnc0.01] were significantly lower than those in the NC group. Cell edema, partial cell necrosis and Tunel staining showed that apoptotic cells increased in CIH group and fibrosis level in CIH group was increased by picric acid-Sirius red staining. The level of HIF-1 伪 was increased by Western Blot [0.62 卤2.89E-0.5CIH] and 0.45 卤0.01ncncncncnctrol (P0.05). Conclusion the chronic intermittent hypoxia in sleep apnea model affects the cardiac function of rats. The chronic intermittent hypoxia in sleep apnea model aggravated myocardial injury and myocardial fibrosis in rats, and increased the expression of hypoxia inducible factor-1 伪 in chronic intermittent hypoxia induced by sleep apnea mode in rats.
【学位授予单位】：东南大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R766

【相似文献】