本文選題：無癥狀舒張功能不全 + 壓力超負(fù)荷��； 參考：《中國人民解放軍軍醫(yī)進(jìn)修學(xué)院》2007年碩士論文

【摘要】： 目的：無癥狀舒張功能不全(Asymptomatic Diastolic Dysfunciton，ADD)是指舒張功能異常、射血分?jǐn)?shù)正常，不伴有心衰的癥狀和體征。ADD患者由于無明顯癥狀，因此臨床上往往忽視這部分患者，相關(guān)研究和報(bào)道也較少。故本研究通過新西蘭兔腹主動(dòng)脈縮窄術(shù)，模擬人類高血壓誘導(dǎo)的ADD的病理生理特點(diǎn)，建立人類高血壓誘導(dǎo)的ADD的動(dòng)物模型，采用超聲心動(dòng)圖、血流動(dòng)力學(xué)、血清和心肌局部神經(jīng)內(nèi)分泌水平、組織形態(tài)學(xué)等多項(xiàng)指標(biāo)綜合評(píng)價(jià)模型的病理生理特點(diǎn)。并在術(shù)后第二日給予倍他樂克，觀察其治療效果。 方法：健康雄性新西蘭兔47只，隨機(jī)分為假手術(shù)組(n=15)、手術(shù)組(n=32)。手術(shù)組在雙側(cè)腎動(dòng)脈分支下方1cm處行腹主動(dòng)脈縮窄術(shù)(外徑縮窄35～40％)；假手術(shù)組作為正常對(duì)照組。術(shù)后觀察兔精神狀態(tài)、飲食、活動(dòng)、體重等指標(biāo)變化。分別于術(shù)前和處死前行血流動(dòng)力學(xué)檢查檢測(cè)心臟功能的變化，于術(shù)前、術(shù)后2周、4周、8周行超聲心動(dòng)圖檢查動(dòng)態(tài)監(jiān)測(cè)心臟結(jié)構(gòu)和功能的變化。酶聯(lián)免疫吸附法(Elisa)檢測(cè)各個(gè)階段血清(0、2、4、8周)和心肌中血管緊張素Ⅱ(AngⅡ)、內(nèi)皮素-1(ET-1)、去甲腎上腺素(NE)和腦型利尿鈉肽前體氨基端肽(NT-proBNP)和尿素酶法檢測(cè)血清尿素氮(BuN)和肌酐(Cr)變化。HE染色觀察心肌形態(tài)學(xué)改變。其中超聲檢查包括M超測(cè)量左室室壁厚度、左室內(nèi)徑，用2切面改良Simpson法測(cè)量左室容積、左室射血分?jǐn)?shù)(LVEF)；用脈沖多普勒測(cè)量二尖瓣血流頻譜E峰、A峰、E峰減速時(shí)間(decelerating time，DT)、A峰持續(xù)時(shí)間(A duration，AD)，右上肺靜脈收縮期S波(PVs)、肺靜脈舒張期D波(PVd)、左房收縮逆向a波時(shí)間(PVa duration，，PVaD)；用彩色M型獲取舒張?jiān)缙谧笫覂?nèi)血流播散速度(early diastolic flow propagation velocity，Vp)；用組織多普勒(tissue Doppler imaging，TDI)在二尖瓣環(huán)室間隔、側(cè)壁、下壁、前壁4處測(cè)量心肌長軸方向的收縮期峰速(Sm)、舒張?jiān)缙诜逅?Em)、舒張晚期峰速(Am)和等容舒張時(shí)間(isovolumic relaxation time，IVRT)等值，計(jì)算E／Em、E／Vp等參數(shù)。血流動(dòng)力學(xué)檢查包括左室收縮壓(LVSP)、左室舒張末壓(LVEDP)、壓力最大上升速率(+dp／dt_(max))、壓力最大下降速率(-dp／dt_(max))、等容舒張期松弛時(shí)間常數(shù)(τ)等指標(biāo)變化。2)將NT-proBNP與EF、Vp、sm、Em、E／Em和E／Vp行相關(guān)分析。3)雄性新西蘭兔24只隨機(jī)分為假手術(shù)組(n=8)、ADD組(n=8)和ADD+藥物治療組(n=8)。藥物治療組于術(shù)后第二日給予倍他樂克(25mg，2／日)，觀察8周，檢測(cè)指標(biāo)同前。 結(jié)果：1)術(shù)后7～8周，部分手術(shù)組兔出現(xiàn)食欲不振和活動(dòng)量減少，但均未出現(xiàn)呼吸困難、肺Up音等明顯心衰的癥狀；而假手術(shù)組兔未出現(xiàn)任何臨床癥狀和體征。2)與假手術(shù)組相比，術(shù)后2周IVSD、LVPWD、LVmass增加(P＜0.000)；4周時(shí)肥厚增加更加明顯，Em降低(P＜0.05)、E／Vp增加(P＜0.05)；8周時(shí)LAV、LVEDD、LVEDV增加(P＜0.05)；Sm(P＜0.01)、Em(P＜0.01)、Vp(P＜0.000)均降低，E／Em(P＜0.05)、E／Vp(P＜0.000)增加。而EF始終保持正常。血流動(dòng)力學(xué)檢查測(cè)定LVEDP增高(P＜0.01)，τ值延長(P＜0.01)。病理檢查提示心肌細(xì)胞肥大。8周時(shí)血清AngⅡ、ET-1、NE、NT-proBNP水平均顯著升高(P＜0.000)，心肌AngⅡ(P＜0.000)、ET-1(P＜0.05)、NE和NT-proBNP(P＜0.01)也升高。3)NT-proBNP與Sm、Em、E／Em和E／Vp均顯著相關(guān)，而與EF相關(guān)性差。4)倍他樂克治療組LVEDP(P＜0.000)、τ(P＜0.05)、IVSD(P＜0.05)、Em(P＜0.05)和E／Vp(P＜0.05)等均明顯改善；血清AngⅡ(P＜0.01)、ET-1(P＜0.05)、NE和NT-proBNP(P＜0.05)也顯著降低。心肌中AngⅡ、ET-1、NE和NT-proBNP均下降(P＜0.05)。 結(jié)論：1)通過縮窄新西蘭兔腎下腹主動(dòng)脈(縮窄比例為35％～40％)，8周時(shí)舒張功能受損、射血分?jǐn)?shù)正常而且無明顯心衰癥狀。觀察16周后超聲和血流動(dòng)力學(xué)指標(biāo)均未發(fā)生明顯變化，說明該模型具有一定的穩(wěn)定性，或許可以作為人類高血壓誘導(dǎo)的ADD的動(dòng)物模型。2)進(jìn)一步通過TDI技術(shù)檢查發(fā)現(xiàn)，ADD以舒張功能受損為主，同時(shí)也伴有收縮功能的輕度損傷。3)血清和心肌中AngⅡ、ET-1、NE和NT-proBNP均升高，可能參與了舒張功能的損傷。4)NT-proBNP與反映左室舒張功能的Em、E／Em、E／Vp也存在良好的相關(guān)性，是檢出舒張功能早期損傷的敏感指標(biāo)。5)倍他樂克可逆轉(zhuǎn)左室肥厚，改善血流動(dòng)力學(xué)和左室舒張功能。6)倍他樂克可降低血清和心肌組織中AngⅡ、ET-1、NE和NT-proBNP水平。
[Abstract]:Objective: asymptomatic diastolic dysfunction (Asymptomatic Diastolic Dysfunciton, ADD) refers to abnormal diastolic function, normal ejection fraction, asymptomatic symptoms and signs of heart failure without symptoms and signs of.ADD patients. Therefore, this part of the patients is often neglected in clinical and less related studies and reports. Pulse constriction, which simulates the pathophysiological characteristics of ADD induced by human hypertension, establishes an animal model of ADD induced by human hypertension. It uses echocardiography, hemodynamics, serum and myocardial local neuroendocrine levels, histomorphology and other indicators to evaluate the pathophysiology of the model and give times more than second days after operation. He Lok, to observe the effect of his treatment.
Methods: 47 healthy male New Zealand rabbits were randomly divided into sham operation group (n=15) and operation group (n=32). Abdominal aorta coarctation (35 to 40%) was performed at 1cm below the bilateral renal artery branch (35 to 40%), and the sham operation group was used as a normal control group. The changes of cardiac function were detected by hemodynamic examination before operation. The changes of cardiac structure and function were monitored dynamically by echocardiography at 2 weeks, 4 weeks and 8 weeks after operation. Enzyme linked immunosorbent assay (Elisa) was used to detect serum (0,2,4,8 weeks) and myocardial angiotensin II (Ang II), endothelin -1 (ET-1), norepinephrine (N). E) and the changes of serum urea nitrogen (BuN) and creatinine (Cr) and serum urea nitrogen (BuN) and creatinine (Cr) changes with brain type diuretic natriuretic peptide (NT-proBNP) and serum urease assay. The echocardiographic examination included M ultra measurement of left ventricular wall thickness, left ventricular diameter, left ventricular volume, left ventricular ejection fraction (LVEF) with 2 cut surface improved Simpson method, and pulse multiple. E peak, A peak, E peak deceleration time (decelerating time, DT), A peak duration (A duration, AD), S wave (PVs) in the right upper pulmonary vein (PVs), pulmonary venous systolic time, and left atrial systolic time were used to measure the velocity of early diastolic blood flow in the left chamber. C flow propagation velocity, Vp); the systolic peak velocity (Sm), early diastolic velocity (Em), late diastolic peak velocity (Em), late diastolic peak velocity (Am) and equal volume diastolic time were measured by tissue Doppler (tissue Doppler imaging, TDI) at the mitral annular space, lateral wall, lower wall, and anterior wall at 4 places. Vp and other parameters. The hemodynamic examination included left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximum pressure rise rate (+dp / dt_ (max)), maximum pressure drop rate (-dp / dt_ (max)), equal volume relaxation time constant (tau) and other indexes changed.2) 24 rabbits were randomly divided into the sham operation group (n=8), the ADD group (n=8) and the ADD+ drug treatment group (n=8). The drug treatment group was given Betaloc (25mg, 2 / day) on the second day after the operation and was observed for 8 weeks.
Results: 1) 1) 7~8 weeks after the operation, there was no appetite and less activity in the rabbits in the operation group, but there was no symptom of dyspnea, lung Up sound and other symptoms of heart failure, while the rabbits in the sham operation group had no clinical symptoms and signs.2), compared with the sham operation group, 2 weeks after the operation, IVSD, LVPWD, LVmass increased (P < 0), and the hypertrophy increased more clearly at 4 weeks. Em decreased (P < 0.05), E / Vp increased (P < 0.05); LAV, LVEDD, LVEDV increased at 8 weeks (P < 0.05); Sm (P < 0.01), Em (0) decreased. Serum Ang II, ET-1, NE, NT-proBNP water increased significantly at.8 weeks (P < 0), Ang II (P < 0), ET-1 (P < 0.05), NE and NT-proBNP (< 0.01). P < 0.05) and E / Vp (P < 0.05) were significantly improved, and serum Ang II (P < 0.01), ET-1 (P < 0.05), NE and NT-proBNP (P < 0.05) were also significantly reduced.
Conclusion: 1) by narrowing the lower abdominal aorta of New Zealand rabbits (the proportion of coarctation is 35% to 40%), the function of Shi Shuzhang is damaged in 8 weeks, the ejection fraction is normal and there is no obvious heart failure symptoms. There is no obvious change in the ultrasonic and hemodynamic indexes after 16 weeks, which indicates that the model has a certain stability and may be used as human hypertension. The induced ADD animal model.2) further through the TDI technique examination, it was found that ADD was mainly diastolic dysfunction, accompanied by a mild injury of.3) in.3) serum and Ang II, ET-1, NE and NT-proBNP in the myocardium, and may be involved in the diastolic function of.4) NT-proBNP and the left ventricular diastolic function. In good correlation,.5 is a sensitive indicator of early diastolic dysfunction. Betaloc can reverse left ventricular hypertrophy, improve hemodynamics and left ventricular diastolic function.6) Betaloc can reduce the level of Ang II, ET-1, NE and NT-proBNP in serum and myocardial tissue.

【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R-332;R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前4條

1 張萍,李志wt,邱健,陸青,周瑛,黃祖堅(jiān);持續(xù)壓力超負(fù)荷對(duì)兔左心室細(xì)胞凋亡的影響[J];第一軍醫(yī)大學(xué)學(xué)報(bào);2002年01期

2 譚小強(qiáng);67例無癥狀左室舒張功能不全患者的治療分析[J];華夏醫(yī)學(xué);2004年01期

3 羅羽慧,李法琦,梅霞,周凱,胡詠梅;福辛普利對(duì)實(shí)驗(yàn)性心力衰竭大鼠心肌細(xì)胞凋亡和Fas、Fas配體基因表達(dá)的影響[J];中國循環(huán)雜志;2004年01期

4 冼紹祥,徐志均,黃衍壽,劉小虹;養(yǎng)心康對(duì)心功能不全動(dòng)物模型的血流動(dòng)力學(xué)研究[J];中藥新藥與臨床藥理;2001年02期

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