發(fā)布時間：2018-06-21 09:40

  本文選題：高血壓 + 大鼠��； 參考：《福建醫(yī)科大學(xué)》2014年碩士論文

【摘要】：背景和目的 心肌纖維化在高血壓心功能不全的發(fā)生中起重要作用，本項目組的前期研究發(fā)現(xiàn)了自發(fā)性高血壓大鼠（SHR）左室結(jié)構(gòu)、心肌膠原纖維含量及收縮期應(yīng)變特征隨著增齡變化的大體趨勢：28周之后出現(xiàn)心肌細(xì)胞肥大、間質(zhì)膠原增生，這些心肌組織重構(gòu)與后期發(fā)生的心肌收縮應(yīng)變逐漸受損及整體舒張功能改變相關(guān)。本研究在進(jìn)一步增加SHR周齡組別的基礎(chǔ)上，觀察了增齡過程心肌不同部位（心內(nèi)膜下層與心外膜下層）膠原分布特點及其與左室心肌多維應(yīng)變、左心整體功能的關(guān)系，探討心肌膠原在SHR左心功能變化中的意義。 方法 購進(jìn)SHR，隨機(jī)分為9組飼養(yǎng)，每組8-10只，在不同周齡時（12W-84W）進(jìn)行研究。以WKY雄性大鼠為對照。觀察指標(biāo)：①左心常規(guī)指標(biāo)：左房左室內(nèi)徑、相對室壁厚度（RWT）及左室質(zhì)量指數(shù)（LVMI），LVEF與FS，二尖瓣口血流速度（E、A）；②二維應(yīng)變（2DSE）指標(biāo)：乳頭肌水平短軸切面獲得峰值徑向應(yīng)變（SR）、周向應(yīng)變(SC)，四腔心切面獲得室間隔與左室側(cè)壁中間段收縮期峰值縱向應(yīng)變（SL）；③組織學(xué)指標(biāo)：取左室中間段心肌切片，Masson染色，測量血管周圍膠原面積（PVCA）及心內(nèi)膜下層、心外膜下層心肌膠原容積分?jǐn)?shù)（CVF）；④心導(dǎo)管指標(biāo)：LVEDP及LV±dp/dtmax等；⑤分析左心結(jié)構(gòu)功能指標(biāo)、收縮應(yīng)變指標(biāo)與纖維化指標(biāo)相關(guān)性。 結(jié)果 1.常規(guī)指標(biāo)：SHR各周齡組均呈高血壓狀態(tài)，45W以后舒張壓繼續(xù)增高（p0.05）；RWT、LVMI隨增齡而增加，分別在28W及36W時出現(xiàn)顯著增加，在75-84W段達(dá)到最大值，二者與同周齡WKY組的差異在75W后才出現(xiàn)，LVEF也在75W后才開始下降（以上均p0.05）；LAD的增加在45W開始有統(tǒng)計學(xué)差異（p0.05）。 2.2DSE指標(biāo)：SHR的SL、SC及SR從12W至28W逐漸上升，28W達(dá)最高（p0.05），SL從45W開始下降（p0.05），而SC、SR從75W才開始下降（p0.05），84W降至最低（p0.05）；與WKY組對比，SHR在75-84W周齡段各方向應(yīng)變均顯著降低（p0.05），同時EF值也開始下降[(77.8±5.7)%vs (69.2±5.9)%, p 0.05]。 3.組織學(xué)變化：SHR的CVF、PVCA隨周齡的增加而增多，且66W開始心內(nèi)膜下層心肌CVF明顯多于心外膜下層，75W后這種差異更大（p0.05），其中心內(nèi)膜下CVF在66W顯著增加（p0.05），而心外膜下CVF在75-84W段才出現(xiàn)顯著增加（p0.05），PVCA也在66W出現(xiàn)顯著增加（p0.05）；與WKY比，SHR在36W段時CVF及PVCA僅呈增加趨勢（p0.05），在75-84W段則顯著增加（p0.05）。 4.心導(dǎo)管指標(biāo)：SHR的LV-dp/dt及LV+dp/dt在28W出現(xiàn)顯著增加（p0.05），75W開始顯著下降（p0.05），而LVEDP在45W及以后才出現(xiàn)增加（p0.05），且明顯高于同周齡WKY大鼠（p0.05）。 5.左室功能指標(biāo)與心肌膠原相關(guān)分析：SL與內(nèi)膜下心肌CVF呈負(fù)相關(guān)（r=-0.47，p=0.002），而與外膜下CVF無明顯相關(guān)；SR、SC與心肌CVF呈負(fù)相關(guān)（值-0.37~-0.41，p0.05），LVEDP也與CVF相關(guān)（r=0.57，p0.01）。結(jié)論 1．SHR與WKY大鼠在28周齡開始均出現(xiàn)不同程度的心肌局部膠原增生，可能屬增齡性變化；SHR與高血壓有關(guān)的病理性心肌纖維化出現(xiàn)于66周以后，表現(xiàn)為心肌膠原比例及血管周圍膠原面積的增加，，由心內(nèi)膜下層向心外膜下層發(fā)展。 2．SHR心肌病理性纖維化的發(fā)生特點與其心室空間多向應(yīng)變受損的發(fā)生次序以及后期的整體功能受損一致：縱向應(yīng)變先受損，當(dāng)周向與徑向應(yīng)變都降低時LVEF降低。這些結(jié)果可能為探討高血壓左心功能不全的發(fā)展提供心肌力學(xué)與病理學(xué)依據(jù)。
[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.
【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2014
【分類號】：R544.1;R445.1

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