本文選題：舒張性心力衰竭 + 兔　； 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】： 背景：舒張性心力衰竭(DHF)是一組具有充血性心力衰竭(CHF)表現(xiàn)、以射血分?jǐn)?shù)(EF)正常而舒張功能受損為特點(diǎn)的臨床癥候群。臨床上有25～40％的CHF患者屬DHF。但是目前尚缺乏一種有效的DHF模型，且EF并不是評(píng)價(jià)收縮功能的敏感指標(biāo)。大規(guī)模臨床試驗(yàn)證實(shí)β受體阻滯劑可降低CHF死亡率，但對(duì)DHF動(dòng)物的治療研究還鮮有報(bào)道。本研究通過縮窄新西蘭兔腹主動(dòng)脈，采用超聲心動(dòng)圖和血流動(dòng)力學(xué)全面評(píng)價(jià)心臟舒縮功能，并結(jié)合病理學(xué)、神經(jīng)內(nèi)分泌和腎功能改變，探索壓力負(fù)荷誘導(dǎo)的DHF模型建立方法。同時(shí)在疾病早期用倍他樂克干預(yù)，觀察其對(duì)DHF的治療作用。 方法：1)雄性新西蘭兔75只隨機(jī)分為假手術(shù)組(n=15)、手術(shù)1組(n=45)和手術(shù)2組(n=15)。手術(shù)1組在右側(cè)腎動(dòng)脈分支上方1cm處行腹主動(dòng)脈縮窄術(shù)(外徑縮窄35～40％)；手術(shù)2組在同一部位將外徑縮窄50～60％。術(shù)后觀察5周。術(shù)前和處死時(shí)用左心導(dǎo)管測(cè)定血流動(dòng)力學(xué)。術(shù)前、術(shù)后2周、4周和5周行超聲心動(dòng)圖檢查。每次超聲檢查后6h內(nèi)從耳中央動(dòng)脈取血并分離血清。血流動(dòng)力學(xué)指標(biāo)有左室收縮壓(LVSP)、左室舒張未壓(LVEDP)、壓力最大上升速率(+dp/dt_(max))、壓力最大下降速率(-dp/dt_(min))和松弛時(shí)間常數(shù)(τ)。用二維超聲測(cè)量左房容積(LAV)；M超測(cè)量室間隔厚度(IVSD)、左室后壁厚度(LVPWD)、左室舒張末容積(LVEDV)、左室收縮末容積(LVESV)、EF及舒張?jiān)缙谧笫覂?nèi)血流播散速度(Vp)；脈沖多普勒檢測(cè)二尖瓣血流舒張?jiān)缙诜逅俣?E)、舒張晚期峰速度(A)、、肺靜脈血流心房收縮期峰速度(PVa)和a峰持續(xù)時(shí)間(PVaD)；組織多普勒檢測(cè)二尖瓣環(huán)收縮期峰值運(yùn)動(dòng)速度(Sm)和舒張?jiān)缙诜逯颠\(yùn)動(dòng)速度(Em)，并計(jì)算E/Em和E/Vp。用酶聯(lián)免疫吸附法檢測(cè)血清與心肌血管緊張素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)濃度，并將NT-proBNP與EF、Sm、Em、E/Em和E/Vp行相關(guān)分析。尿素酶法檢測(cè)血清尿素氮(BUN)和肌酐(Cr)變化。2)雄性新西蘭兔30只隨機(jī)分為假手術(shù)組(n=6)、手術(shù)組(n=12)和手術(shù)治療組(n=12)。手術(shù)方法同手術(shù)1組，手術(shù)治療組從術(shù)后第1天起應(yīng)用倍他樂克(25mg，2/日)治療，觀察4周，檢測(cè)指標(biāo)同前。3)SPSS13.0統(tǒng)計(jì)分析，P＜0.05為有顯著差異。 結(jié)果：1)手術(shù)1組有22只兔術(shù)后26～30天出現(xiàn)精神萎靡、食欲不振、呼吸困難等心衰表現(xiàn)，手術(shù)2組有6只兔術(shù)后6～10天因急性肺水腫死亡。2)手術(shù)1組兔術(shù)后2周出現(xiàn)IVSD、LVPWD增加(P＜0.000)和LAV、LVEDV擴(kuò)大(P＜0.01)；Sm(P＜0.05)、Em(P＜0.05)、Vp(P＜0.000)均降低，E/Em(P＜0.01)、E/Vp(P＜0.05)增加。術(shù)后4～5周上述指標(biāo)變化更加明顯，而EF無改變。LVEDP和τ值也顯著增高(P＜0.000)，-dp/dt_(min)下降明顯(P＜0.01)。血清和心肌AngⅡ、ET-1、NE、NT-proBNP(P＜0.000，P＜0.01)及BUN與Cr(P＜0.000)水平均升高。3)手術(shù)2組LAV(P＜0.000)、LVEDV(P＜0.05)、LVESV(P＜0.000)擴(kuò)大明顯，Sm(P＜0.000)、Em(P＜0.01)、Vp(P＜0.000)、E/Em(P＜0.05)和E/Vp(P＜0.01)顯著改變，EF降至50％以下(P＜0.000)。LVEDP、τ、-dp/dt_(max)和+dp/dt_(min)也存在明顯變化(P＜0.000)。血清和心肌各項(xiàng)指標(biāo)變化更加明顯。4)NT-proBNP與Sm、Em、E/Em和E/Vp均顯著相關(guān)(P＜0.000)，而與EF相關(guān)性差(r=-0.395)。5)倍他樂克治療組僅1只兔出現(xiàn)心衰表現(xiàn)，，其余兔的精神飲食活動(dòng)情況尚可。與手術(shù)組相比，手術(shù)治療組兔LVEDP(P＜0.000)、τ(P＜0.000)、LAV(P＜0.01)、IVSD(P＜0.05)、Em(P＜0.05)和E/Em(P＜0.05)均明顯改善；血清AngⅡ、ET-1(P＜0.01)和血清與心肌NE、NT-proBNP(P＜0.01，P＜0.05)顯著降低；BUN、Cr無變化。 結(jié)論：1)通過縮窄新西蘭兔腎動(dòng)脈分支上方的腹主動(dòng)脈(外徑縮窄35～40％)，26～30天可出現(xiàn)心衰表現(xiàn)，-dp/dt_(min)、Vp和Em顯著降低，LVEDP、τ、E/Em和E/Vp明顯增高而EF正常，可以作為人類高血壓病導(dǎo)致的DHF動(dòng)物模型；2)縮窄兔腹主動(dòng)脈后出現(xiàn)Sm降低，提示收縮功能損傷可能也參與DHF的發(fā)病過程；3)循環(huán)和心肌局部神經(jīng)內(nèi)分泌系統(tǒng)激活可能是導(dǎo)致DHF的重要機(jī)制；4)NT-proBNP與Sm、Em、E/Em和E/Vp顯著相關(guān)，與EF相關(guān)性差；5)倍他樂克可有效減輕DHF兔的心室肥厚、心腔擴(kuò)大和舒縮功能損傷，抑制神經(jīng)內(nèi)分泌系統(tǒng)激活。
[Abstract]:Background: diastolic heart failure (DHF) is a group of clinical syndromes with congestive heart failure (CHF) manifestations, characterized by normal EF and impaired diastolic function. 25 to 40% of CHF patients are clinically DHF. but there is a lack of an effective DHF model, and EF is not a sensitive index for evaluating contractile function. The clinical trial verified that beta blockers can reduce the mortality of CHF, but there are few reports on the treatment of DHF animals. By narrowing the abdominal aorta of New Zealand rabbits, echocardiography and hemodynamics were used to evaluate the cardiac systolic and systolic function, and to explore the pressure load induction combined with pathology, neuroendocrine and renal function changes. To establish a DHF model, and to observe the therapeutic effect of Betaloc on DHF in the early stage of the disease.
Methods: 1) 75 male New Zealand rabbits were randomly divided into sham operation group (n=15), operation 1 groups (n=45) and operation 2 group (n=15). The 1 group underwent abdominal aorta coarctation (35 to 40%) at the right part of the right branch of the right renal artery (35 to 40%), and 2 groups narrowed the outer diameter for 5 weeks after 50 to 60%. in the same site. Left cardiac catheterization was used before and when the operation was executed. Hemodynamics was measured. Echocardiography was performed 2 weeks, 4 and 5 weeks after operation. Blood and serum were removed from the central ear artery in 6h after each ultrasound examination. The hemodynamic indexes were left ventricular systolic pressure (LVSP), left ventricular diastolic Unpressure (LVEDP), maximum pressure rise rate (+dp/dt_ (max)), and the maximum pressure drop rate (-dp/dt_ (min)) He Song. Relaxation time constant (tau). Measurement of left atrial volume (LAV) with two-dimensional ultrasound; M super measurement of ventricular septum thickness (IVSD), left ventricular posterior wall thickness (LVPWD), left ventricular end diastolic volume (LVEDV), left ventricular end systolic volume (LVESV), EF and early diastolic flow velocity (Vp) in left chamber; pulse Doppler detection of early diastolic peak velocity (E) and late relaxation of mitral valve flow (E), and late relaxation Peak velocity (A), atrial systolic peak velocity (PVa) and a peak duration (PVaD) of pulmonary venous blood flow; tissue Doppler detected peak systolic velocity (Sm) and early diastolic peak velocity (Em) in the mitral annulus, and determined the serum and myocardial angiotensin II (Ang II) and endothelin -1 (ET-) by enzyme linked immunosorbent assay (E/Em and E/Vp.). 1) the concentration of norepinephrine (NE) and brain type natriuretic peptide amino end peptide (NT-proBNP), and the correlation analysis between NT-proBNP and EF, Sm, Em, E/Em and E/Vp. The Urease method was used to detect the serum urea nitrogen (BUN) and creatinine (Cr) change.2). 30 male New Zealand rabbits were randomly divided into sham operation group (n=6), operation group and surgical treatment group. In the 1 groups, the treatment group was treated with betaloc (25mg, 2/ day) from first days after the operation, and observed for 4 weeks, and the test index was same as the former.3) SPSS13.0 statistical analysis. There were significant differences in P < 0.05.
Results: 1) in the 1 groups, there were 22 rabbits in the operation, 26~30 days after the operation of 22 rabbits, which showed mental malaise, poor appetite, dyspnea and other heart failure. The 2 group had 6 rabbits who died of acute pulmonary edema on 6~10 days after the operation in the 2 group, and the operation of 1 rabbits appeared at 2 weeks after the operation. LVPWD increased (P < 0) and LAV, LVEDV enlarged (P < 0.01); Sm (P < 0.05), Em (P < 0.05), Vp (Vp < 0) were all. Decrease, E/Em (P < 0.01), E/Vp (P < 0.05) increased. The changes of the above indexes were more obvious after 4~5 weeks, while EF without change of.LVEDP and tau increased significantly (P < 0), -dp/dt_ (min) decreased significantly (P < 0.01). 0), LVEDV (P < 0.05), LVESV (P < 0) expanded obviously, Sm (P < 0), Em (P < 0.01), Vp (P < 0), E/Em (P < 0.05) and P < 0.01). Both E/Em and E/Vp were significantly correlated (P < 0), but with EF correlation (r=-0.395).5), only 1 rabbits in the treatment group had heart failure, and the rest of the rabbits were still in the mental diet. Compared with the operation group, the operation group had LVEDP (P < 0), tau (P < 0), LAV (P < 0.05), IVSD (0.05) and 0.05 < 0.05). Improvement: serum Ang II, ET-1 (P < 0.01), serum and myocardial NE, NT-proBNP (P < 0.01, P < 0.05) significantly decreased; BUN and Cr did not change.
Conclusion: 1) by narrowing the abdominal aorta above the renal artery branch of New Zealand rabbits (the outer diameter narrowed from 35 to 40%), the expression of heart failure could appear on 26~30 days. -dp/dt_ (min), Vp and Em were significantly reduced, LVEDP, tau, E/Em and E/Vp were significantly increased and EF normal, and can be used as the DHF animal model caused by human hypertension; 2) Sm descending after the abdominal aorta of narrowing rabbit. Low, suggesting that contractile dysfunction may also participate in the pathogenesis of DHF; 3) circulation and activation of local neuroendocrine system may be an important mechanism for DHF; 4) NT-proBNP is significantly related to Sm, Em, E/Em and E/Vp, and is poor with EF; 5) Betaloc can effectively reduce ventricular hypertrophy, dilation of heart cavity and impairment of systolic function in DHF rabbits, Inhibition of the activation of the neuroendocrine system.
【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;R541.6

【引證文獻(xiàn)】

相關(guān)期刊論文 前4條

1 張曉丹;柏勝男;張彩霞;張?zhí)煲?;葛根素對(duì)舒張性心力衰竭大鼠心肌僵硬度和心肌組織Ⅰ型、Ⅲ型膠原表達(dá)的影響[J];現(xiàn)代藥物與臨床;2012年03期

2 柏勝男;;大鼠舒張性心力衰竭動(dòng)物模型的建立[J];黑龍江醫(yī)藥;2011年06期

3 張?zhí)煲?;舒張性心力衰竭大鼠模型的建立[J];黑龍江醫(yī)藥;2011年06期

4 張曉丹;渠永清;張婷姍;張琪;;�；撬釋�(duì)舒張性心力衰竭大鼠心肌細(xì)胞鈣超載的拮抗作用[J];中國中藥雜志;2009年03期

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