自发性高血压大鼠左室心肌胶原与心肌力学特征关系的探讨

发布时间：2018-06-21 09:40

本文选题：高血压 + 大鼠　；参考：《福建医科大学》2014年硕士论文

【摘要】：背景和目的心肌纤维化在高血压心功能不全的发生中起重要作用，本项目组的前期研究发现了自发性高血压大鼠（SHR）左室结构、心肌胶原纤维含量及收缩期应变特征随着增龄变化的大体趋势：28周之后出现心肌细胞肥大、间质胶原增生，这些心肌组织重构与后期发生的心肌收缩应变逐渐受损及整体舒张功能改变相关。本研究在进一步增加SHR周龄组别的基础上，观察了增龄过程心肌不同部位（心内膜下层与心外膜下层）胶原分布特点及其与左室心肌多维应变、左心整体功能的关系，探讨心肌胶原在SHR左心功能变化中的意义。方法购进SHR，随机分为9组饲养，每组8-10只，在不同周龄时（12W-84W）进行研究。以WKY雄性大鼠为对照。观察指标：①左心常规指标：左房左室内径、相对室壁厚度（RWT）及左室质量指数（LVMI），LVEF与FS，二尖瓣口血流速度（E、A）；②二维应变（2DSE）指标：乳头肌水平短轴切面获得峰值径向应变（SR）、周向应变(SC)，四腔心切面获得室间隔与左室侧壁中间段收缩期峰值纵向应变（SL）；③组织学指标：取左室中间段心肌切片，Masson染色，测量血管周围胶原面积（PVCA）及心内膜下层、心外膜下层心肌胶原容积分数（CVF）；④心导管指标：LVEDP及LV±dp/dtmax等；⑤分析左心结构功能指标、收缩应变指标与纤维化指标相关性。结果 1.常规指标：SHR各周龄组均呈高血压状态，45W以后舒张压继续增高（p0.05）；RWT、LVMI随增龄而增加，分别在28W及36W时出现显著增加，在75-84W段达到最大值，二者与同周龄WKY组的差异在75W后才出现，LVEF也在75W后才开始下降（以上均p0.05）；LAD的增加在45W开始有统计学差异（p0.05）。 2.2DSE指标：SHR的SL、SC及SR从12W至28W逐渐上升，28W达最高（p0.05），SL从45W开始下降（p0.05），而SC、SR从75W才开始下降（p0.05），84W降至最低（p0.05）；与WKY组对比，SHR在75-84W周龄段各方向应变均显著降低（p0.05），同时EF值也开始下降[(77.8±5.7)%vs (69.2±5.9)%, p 0.05]。 3.组织学变化：SHR的CVF、PVCA随周龄的增加而增多，且66W开始心内膜下层心肌CVF明显多于心外膜下层，75W后这种差异更大（p0.05），其中心内膜下CVF在66W显著增加（p0.05），而心外膜下CVF在75-84W段才出现显著增加（p0.05），PVCA也在66W出现显著增加（p0.05）；与WKY比，SHR在36W段时CVF及PVCA仅呈增加趋势（p0.05），在75-84W段则显著增加（p0.05）。 4.心导管指标：SHR的LV-dp/dt及LV+dp/dt在28W出现显著增加（p0.05），75W开始显著下降（p0.05），而LVEDP在45W及以后才出现增加（p0.05），且明显高于同周龄WKY大鼠（p0.05）。 5.左室功能指标与心肌胶原相关分析：SL与内膜下心肌CVF呈负相关（r=-0.47，p=0.002），而与外膜下CVF无明显相关；SR、SC与心肌CVF呈负相关（值-0.37~-0.41，p0.05），LVEDP也与CVF相关（r=0.57，p0.01）。结论 1．SHR与WKY大鼠在28周龄开始均出现不同程度的心肌局部胶原增生，可能属增龄性变化；SHR与高血压有关的病理性心肌纤维化出现于66周以后，表现为心肌胶原比例及血管周围胶原面积的增加，，由心内膜下层向心外膜下层发展。 2．SHR心肌病理性纤维化的发生特点与其心室空间多向应变受损的发生次序以及后期的整体功能受损一致：纵向应变先受损，当周向与径向应变都降低时LVEF降低。这些结果可能为探讨高血压左心功能不全的发展提供心肌力学与病理学依据。
[Abstract]:Background and purpose
Myocardial fibrosis plays an important role in the occurrence of hypertensive cardiac insufficiency. Earlier studies in this project found the left ventricular structure of spontaneously hypertensive rats (SHR), the general trend of myocardial collagen fiber content and systolic strain characteristics along with the age of aging: after 28 weeks, cardiomyocyte hypertrophy, interstitial collagen hyperplasia, these myocardium were found. Tissue remodeling is associated with gradual impairment of myocardial contractile strain and changes in overall diastolic function. In this study, the distribution of collagen distribution in different parts of the myocardium (subendocardium and subepicardial layer), the multidimensional strain of the left ventricular myocardium and the overall function of the left heart were observed on the basis of further increasing the age group of SHR weeks. To investigate the significance of myocardial collagen in the change of left ventricular function of SHR.
Method
SHR was randomly divided into 9 groups, 8-10 rats in each group, at different weeks of age (12W-84W), with WKY male rats as the control. The observation indexes: the left ventricular internal diameter, relative wall thickness (RWT) and left ventricular mass index (LVMI), LVEF and FS, mitral valve flow velocity (E, A); 2. 2 dimensional strain (2DSE) index: milk The peak radial strain (SR), circumferential strain (SC), and four cavities were obtained by the short axis tangential surface of the head muscle. The peak systolic peak longitudinal strain (SL) of the interventricular septum and the middle segment of the left ventricle was obtained. 3. Histological indexes: the myocardial section of the middle segment of the left ventricle, Masson staining, the measurement of the area of collagen around the vessels (PVCA) and the subendocardial subendocardium, and the subendocardial submucosa, and the subepicardial sublayer myocardium Collagen volume fraction (CVF); the cardiac catheterization index: LVEDP and LV + dp/dtmax; the analysis of left ventricular structure and function index, correlation index and fibrosis index. Shrinkage strain
Result
1. routine indicators: all weeks of SHR age group showed high blood pressure state, after 45W diastolic pressure continued to increase (P0.05); RWT, LVMI increased with age, respectively in 28W and 36W, respectively, in 75-84W segment reached the maximum value, the difference between the two and the same week old WKY group appeared after 75W, LVEF also began to decline after 75W (all above); dialectical There was a statistical difference at the beginning of 45W (P0.05).
2.2DSE index: the SL, SC and SR of SHR gradually rise from 12W to 28W, and 28W reaches the highest (P0.05), and SL begins to drop from 45W (P0.05). 0.05].
3. the changes of histology: CVF and PVCA of SHR increased with the increase of the week age, and the CVF in the endocardium of 66W was more than that of the subepicardial layer. After 75W, the difference was greater (P0.05), and the central subintimal CVF in the center increased significantly (P0.05), while the CVF under the epicardium increased significantly in 75-84W segments. 05), compared with WKY, SHR and CVF increased only in 36W segment (P0.05), and increased significantly in 75-84W segment (P0.05).
4. cardiac catheterization index: LV-dp/dt and LV+dp/dt SHR in 28W was significantly increased (P0.05), 75W (P0.05), a significant decrease in 45W and LVEDP and later increased (P0.05), and was significantly higher than the same week old WKY rats (P0.05).
Related analysis of myocardial collagen function index: 5. left ventricular subendocardial myocardial SL and CVF were negatively correlated (r=-0.47, p=0.002), and CVF had no significant correlation with the outer membrane; SR, SC was negatively correlated with myocardial CVF (value -0.37~-0.41, P0.05, LVEDP) is also associated with CVF (r=0.57, P0.01) on the node.
1.SHR and WKY rats have different degrees of myocardial local collagen proliferation at the beginning of 28 weeks of age, which may be age-related changes. The pathological myocardial fibrosis associated with hypertension appears after 66 weeks, showing the proportion of collagen and the increase of collagen area around the blood vessels, from the subendocardium to the outer layer of the epicardial outer membrane.
The characteristics of 2.SHR myocardial pathological fibrosis are in accordance with the sequence of ventricular spatial multidirectional strain damage and the damage to the overall function in the later period. The longitudinal strain is damaged first and the LVEF decreases when the circumferential and radial strain is reduced. These results may be the study of the development of myocardial mechanics and pathology of the left heart work insufficiency of hypertension. Learn the basis.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R544.1;R445.1

【参考文献】