本文關(guān)鍵詞： 鈣穩(wěn)態(tài) 美托洛爾 舒張性心功能不全 益氣活血藥　出處：《北京中醫(yī)藥大學(xué)》2017年博士論文　論文類型：學(xué)位論文

【摘要】：心力衰竭是21世紀(jì)最常見的心血管流行病之一。其中近50%的心衰患者屬于舒張性心功能不全,表現(xiàn)為射血分?jǐn)?shù)正�；虮Ａ舻男乃�(heart failure with preserved ejection fraction,HFpEF),其5年生存率僅30%。近20年來,與收縮性心衰防治已經(jīng)取得的進(jìn)展相比,舒張性心衰的發(fā)病率與病死率沒有明顯減少,其防治形勢十分嚴(yán)峻,已成為心衰研究的難點與熱點。心肌細(xì)胞鈣穩(wěn)態(tài)是鈣離子分布及時相變化的動態(tài)過程,通過興奮-收縮耦聯(lián)機(jī)制直接影響心肌細(xì)胞的舒縮功能。心肌細(xì)胞鈣穩(wěn)態(tài)異常貫穿于病理狀態(tài)下心肌代償性肥厚至舒張功能障礙,再到舒張性功能不全的全過程。蛋白激酶CaMK Ⅱ介導(dǎo)的肌漿網(wǎng)收縮期鈣釋放及舒張期鈣回攝是調(diào)節(jié)心肌細(xì)胞舒縮功能的關(guān)鍵環(huán)節(jié),也是潛在的重要干預(yù)靶點,目前臨床仍缺乏可有效作用于該靶點的藥物。不論HFpEF或收縮性心衰,均可出現(xiàn)心悸、氣短、乏力疲倦、胸悶、活動后加重,甚至喘息氣促等氣虛的證候表現(xiàn),并可伴有唇甲色暗、舌質(zhì)紫暗、瘀斑、瘀點等血瘀證征象�；谂R證經(jīng)驗及證候規(guī)律研究,氣虛血瘀被認(rèn)為是HFpEF的基本病機(jī),貫穿于HFpEF發(fā)生發(fā)展的始終�；谶@一認(rèn)識開展的臨床研究證實益氣活血方藥在改善HFpEF患者氣虛血瘀證的同時,可顯著改善心臟舒張功能;我們的前期研究也發(fā)現(xiàn)益氣活血方藥可改善壓力負(fù)荷大鼠左室舒張功能及肥大心肌細(xì)胞的舒縮功能,并對鈣轉(zhuǎn)運產(chǎn)生良性調(diào)節(jié)作用。但益氣藥、活血藥或益氣活血藥不同配伍對HFpEF是否存在不同影響及其相關(guān)機(jī)制仍需進(jìn)一步驗證。本研究擬通過復(fù)制縮窄腹主動脈致壓力負(fù)荷HFpEF大鼠模型,運用小動物超聲、左心室懸浮導(dǎo)管、激光共聚焦技術(shù)、Western blot等技術(shù),從整體、組織、細(xì)胞及分子水平驗證"益氣活血藥物可能通過調(diào)節(jié)心肌細(xì)胞鈣穩(wěn)態(tài),改善心肌舒張功能,起到延緩甚至阻斷舒張功能不全的作用,并且益氣活血藥物不同配伍之間存在療效差異"假說的科學(xué)性。方法:1.動物造模:采用改良縮窄腹主動脈術(shù)復(fù)制壓力負(fù)荷HFpEF大鼠模型。2.分組及給藥:除假手術(shù)組外,術(shù)后各組大鼠隨機(jī)分為模型組(給予生理鹽水),益氣組(給予黃芪+黨參),活血組(給予丹參+三七),益氣活血1:1組(黃芪+黨參vs丹參+三七=1:1),益氣活血2:1組(黃芪+黨參vs丹參+三七=2:1),美托洛爾組。3.檢測方法及指標(biāo):(1)術(shù)后每周記錄大鼠一般情況,包括體重、癥狀、體征、死亡情況;術(shù)后4周、12周小動物超聲評價左室心功能,包括舒張期左室前后壁厚度,左室內(nèi)徑,左室射血分?jǐn)?shù),短軸縮短率,二尖瓣口前向血流速E峰與二尖瓣環(huán)運動幅度e峰比值;術(shù)后12周大鼠跑臺檢測運動耐力,左心室懸浮導(dǎo)管測量模型大鼠血流動力學(xué)參數(shù)以評價左室心功能;術(shù)后12周處死動物,采靜脈血測量血漿血小板凝集速率、纖維蛋白原含量,并取材計算標(biāo)化心臟重量及肺重量;(2)術(shù)后12周處死動物,急性分離左心室心肌細(xì)胞,利用激光共聚焦技術(shù)檢測心肌細(xì)胞舒縮功能及鈣釋放、鈣回攝狀態(tài);取心肌組織,Western blot法檢測鈣轉(zhuǎn)運相關(guān)蛋白CaMK Ⅱ、PKA、NCX1、PLB(S16)、PLB(T17)、SERCA2a、RyR2 表達(dá)水平。結(jié)果:(1)模型評價:與假手術(shù)組相比,①術(shù)后12周,模型大鼠心肌出現(xiàn)間質(zhì)纖維化及血管周圍纖維化,左室前后壁顯著增厚(P0.05),E/e顯著增高(平均值大于15)(P0.05),標(biāo)化心臟重量、肺重量顯著增加(P0.05),運動耐力下降(P0.05),舒張期左室壓力下降速率-dp/dt降低(P0.05),左室舒張末期壓力增高(靜息約12mmHg,負(fù)荷約16mmHg)(P0.05),頸動脈壓力明顯增高(P0.05);左室射血分?jǐn)?shù)、短軸縮短率、收縮期左室壓力上升速率下降(P0.05),但射血分?jǐn)?shù)均大于50%,收縮功能尚正常;②模型大鼠心肌細(xì)胞舒張期下降速率-d1/dt減慢(P0.05),收縮期上升速率+d1/dt下降(P0.05),收縮最大幅度50%時間增加(P0.05);模型大鼠鈣瞬變最大幅度50%時間延長(P0.05),鈣回落50%時間增加(P0.05),舒張期鈣消除時間常數(shù)(P0.05)及鈣泄漏增大(P0.05),鈣儲備降低(P0.05),鈣轉(zhuǎn)運相關(guān)蛋白表達(dá)水平異常,表現(xiàn)為CaMK Ⅱ、PKA、NCX1、N/S(NCX1/SERCA2a)表達(dá)水平上升(P0.05),PLB(S16)、PLB(T17)、SERCA2a 表達(dá)水平下降(P0.05)。此外,模型大鼠出現(xiàn)以運動耐力下降為主的氣虛證表現(xiàn)(P0.05)及以纖維蛋白原含量升高為主的血瘀證表現(xiàn)(P0.05)。(2)益氣活血藥物對壓力負(fù)荷HFpEF大鼠標(biāo)化心肺重量、心肌纖維化、證候主要表現(xiàn)干預(yù)作用:術(shù)后12周①與模型組比較,各干預(yù)組標(biāo)化心肺重量均降低(均P0.05);干預(yù)組間比較,益氣活血1:1組、益氣活血2:1組標(biāo)化心臟重量改善優(yōu)于活血組(P0.05),標(biāo)化肺重量改善益氣活血2:1組優(yōu)于益氣組、活血組、美托洛爾組(P0.05),但益氣活血2:1組與益氣活血1:1間比較標(biāo)化心肺重量無差異(P0.05);②與模型組相比,僅益氣活血2:1組可降低模型大鼠心肌組織纖維化評分(P0.05);③與模型組比較,益氣組、益氣活血1:1組,益氣活血2:1組可改善反映氣虛證的力竭距離、力竭時間(P0.05);干預(yù)組間比較,益氣活血2:1組力竭距離、力竭時間優(yōu)于益氣組、益氣活血1:1組(均P0.05);只有活血組、美托洛爾組可降低反映血瘀證的纖維蛋白原含量(P0.05),益氣組、益氣活血1:1組、益氣活血2:1組有降低纖維蛋白原含量的趨勢,但無統(tǒng)計學(xué)意義(P0.05);僅活血組降低血小板最大聚集率有統(tǒng)計學(xué)差異(P0.05),其余各干預(yù)組均無統(tǒng)計學(xué)差異(PO.05),但顯示出下降趨勢。(3)益氣活血藥物對壓力負(fù)荷HFpEF大鼠左室舒縮功能的干預(yù)作用:術(shù)后12周,①益氣活血2:1組與模型組比較,可顯著改善左室射血分?jǐn)?shù)(P0.05);與模型組比較,益氣組、美托洛爾組舒張期左室前后壁厚度降低(P0.05),活血組各指標(biāo)無差異(P0.05),益氣活血1:1組、益氣活血2:1組不僅可降低舒張期左室前后壁厚度(P0.05),還可降低E/e比值(P0.05),但兩組間比較無差異(P0.05);②左心室懸浮導(dǎo)管測定心肌舒張功能—靜息狀態(tài)下,與模型組比較,益氣活血2:1組、益氣活血1:1組可顯著降低左室舒張末期壓力(P0.05),益氣活血2:1組可顯著增大左室舒張期壓力下降速率-dp/dt(P0.05),且益氣活血2:1組改善左室舒張末期壓力優(yōu)于益氣活血1:1組(P0.05);多巴胺負(fù)荷狀態(tài)下,與模型組比較,益氣活血2:1組、益氣活血1:1組可顯著降低左室舒張末期壓力、增大-dp/dt(P0.05);益氣活血2:1組改善-dp/dt療效優(yōu)于益氣活血1:1組(P0.05)。(4)益氣活血藥物對壓力負(fù)荷HFpEF大鼠心肌細(xì)胞舒縮功能、鈣穩(wěn)態(tài)及鈣轉(zhuǎn)運關(guān)鍵蛋白的干預(yù)作用:術(shù)后12周,①心肌細(xì)胞收縮功能—與模型組比較,益氣組、益氣活血1:1組、益氣活血2:1組可顯著縮短心肌細(xì)胞收縮最大幅度50%的時間(P0.05);干預(yù)組間比較,益氣活血1:1組、益氣活血2:1組改善心肌細(xì)胞收縮最大幅度50%的時間優(yōu)于益氣組(P0.05),益氣活血1:1組、2:1組間無統(tǒng)計學(xué)差異(P0.0.5);舒張功能—與模型組比較,各干預(yù)組均可改善心肌細(xì)胞舒張50%的時間(P0.05);干預(yù)組間比較,益氣活血2:1組改善心肌細(xì)胞舒張50%的時間優(yōu)于益氣組(P0.05);益氣活血2:1組、益氣活血1:1組、美托洛爾組改善心肌細(xì)胞舒張50%的時間優(yōu)于活血組(P0.05);益氣活血1:1組、2:1組間比較無差異(P0.05);②心肌細(xì)胞鈣釋放—與模型組比較,活血組、美托洛爾組可降低心肌細(xì)胞鈣瞬變幅度(P0.05),益氣組、益氣活血1:1組、益氣活血2:1組可縮短鈣瞬變最大幅度50%時間(P0.05),三組間比較無差異(P0.05);心肌細(xì)胞鈣回攝—與模型組相比,益氣組、益氣活血1:1組、益氣活血2:1組對鈣回落50%時間、鈣消除時間常數(shù)Tau值有改善作用(P0.05),三組間比較無差異(P0.05);活血組、美托洛爾組各指標(biāo)無統(tǒng)計學(xué)差異(P0.05));鈣泄漏及鈣儲備:與模型組相比,僅益氣活血2:1組可減少心肌細(xì)胞鈣泄漏(P0.05);各組與模型組比較鈣庫儲備均無差異(P0.05);③鈣轉(zhuǎn)運關(guān)鍵蛋白表達(dá)水平:與模型組比較,各干預(yù)藥物均可降低鈣轉(zhuǎn)運關(guān)鍵蛋白CaMK Ⅱ、PKA的表達(dá)水平及NCX1/SERCA2a(N/S)比值(P0.05),僅益氣活血2:1組可降低鈣釋放相關(guān)蛋白RyR2的表達(dá)并升高鈣回攝相關(guān)蛋白SERCA2a的表達(dá)(P0.05)),益氣組、益氣活血1:1組、益氣活血2:1組可降低NCX1的表達(dá)水平(P0.05),益氣組、益氣活血2:1組還可升高鈣回攝相關(guān)蛋白PLB(S16)、PLB(T17)的表達(dá)水平(P0.05),美托洛爾組可升高PLB(T17)表達(dá)水平(PP0.05);干預(yù)組間比較,益氣活血2:1組改善CaMK Ⅱ、PKA優(yōu)于益氣組,改善N/S水平優(yōu)于活血組、美托洛爾組(P0.05)),其余各干預(yù)組間未見明顯差異(P0.05)。結(jié)論:1.益氣組在改善運動耐力、左室重構(gòu)、左室舒張功能、心肌細(xì)胞舒縮功能、鈣回攝及升高PLB磷酸化位點的表達(dá)量方面優(yōu)于活血組。2.整體上,益氣活血配伍組防治舒張性心功能不全療效優(yōu)于單純的益氣、活血和美托洛爾組。3.重用益氣藥物的益氣活血配伍組防治舒張性心功能不全療效優(yōu)于常規(guī)益氣活血配伍組。
[Abstract]:Heart failure is one of the most common cardiovascular disease in twenty-first Century. Nearly 50% of patients with heart failure are diastolic dysfunction, manifested as normal ejection fraction or heart failure with preserved (heart failure with preserved ejection fraction, HFpEF), the 5 year survival rate of 30%. for nearly 20 years, compared with the progress and Prevention of systolic heart failure has the incidence and mortality of diastolic heart failure is not significantly reduced, the control situation is very serious, has become the focus and difficulty of heart failure research. Myocardial calcium homeostasis is calcium ion distribution change dynamic process, through the excitation contraction coupling mechanism directly affect the myocardial systolic and diastolic function. Myocardial cell abnormal calcium homeostasis throughout the pathological state of myocardial hypertrophy and diastolic dysfunction, and then to the whole process of diastolic dysfunction. The sarcoplasmic reticulum protein kinase CaMK II mediated charge Systolic and diastolic calcium calcium release back to the camera is a key step in regulating cardiomyocyte contractile function, but also an important potential target for intervention, the clinical effect of the drug is still lack effectively on this target. Whether HFpEF or systolic heart failure may occur, palpitations, shortness of breath, fatigue, chest tightness, aggravated by activities, symptoms even breathing shortness of breath, Qi deficiency, accompanied by a lip color dark, dark purple tongue, ecchymosis petechiae, etc. blood stasis signs. Study on clinical experience and regularity of TCM syndrome based on Qi deficiency and blood stasis is the basic pathogenesis of HFpEF, through the development of HFpEF. The clinical research always understanding of the confirmation of Yiqi Huoxue Prescription on improving HFpEF patients with Qi deficiency and blood stasis based, can significantly improve cardiac diastolic function; our previous studies also found that Yiqi Huoxue Decoction can improve left ventricular pressure overload hypertrophy and diastolic function in rats Myocardial systolic and diastolic function, and have a positive regulatory role on calcium transport. But the Yiqi Huoxue drugs or medicine Yiqi Huoxue Decoction in different combinations on HFpEF if there are different effects and mechanisms still need further verification. This study intends to copy by constriction of abdominal aorta in HFpEF rats model induced by pressure overload, the use of small animal ultrasound. Left ventricular catheter suspension, confocal laser technology, Western blot technology, from the whole, tissue, cellular and molecular level verification of "Yiqi Huoxue drugs may be through the regulation of myocardial cell calcium homeostasis, improve the myocardial diastolic function, to delay or even stop the vasodilation dysfunction, science and efficacy differences between different hypothesis the compatibility of Yiqi Huoxue drugs. Methods: 1. animal model: coarctation of abdominal aorta was made pressure overload rat model of HFpEF.2. by using the modified grouping and administration: except the sham operation group after operation. The rats were randomly divided into model group (saline group), Qi (Huangqi dangshen +), Huoxue group (Salvia miltiorrhiza + 37), 1:1 group (Astragalus Yiqi Huoxue + Salvia miltiorrhiza Codonopsis vs + 37 =1:1), 2:1 group (Astragalus Yiqi Huoxue + Salvia miltiorrhiza Codonopsis vs + 37 =2:1), the United States Metoprolo group.3. detection methods and indicators: (1) a week after operation, the general condition of rats, including body weight, symptoms, signs and death; after 4 weeks, 12 weeks of small animal ultrasound assessment of left ventricular cardiac function, including before and after the left ventricular diastolic wall thickness, left ventricular diameter, left ventricular ejection fraction, short shortening of mitral valve, forward blood flow velocity of mitral annular motion amplitude of peak E and e peak ratio; endurance testing exercise rats 12 weeks after operation, left ventricular catheter suspension measurement model rats with hemodynamic parameters of left ventricular function evaluation; animal were sacrificed 12 weeks after operation, the venous blood platelet plasma measurement agglutination rate, fiber The content of fibrinogen, and were normalized heart weight and lung weight; (2) animal were sacrificed 12 weeks after surgery, acute left ventricular myocytes were isolated myocardial cells were detected in Shu focusing technique and diastolic function and calcium release calcium by laser shooting back state; myocardium Western, blot assay of calcium transport related protein CaMK II, PKA, NCX1, PLB (S16), PLB (T17), SERCA2a, the expression level of RyR2. Results: (1) evaluation model: compared with sham operation group, 12 weeks after operation, the rats model of myocardial fibrosis and around vascular fibrosis, left ventricular wall thickening (P0.05 (E/e), significantly higher mean values greater than 15) (P0.05), the heart weight, lung weight increased significantly (P0.05), decreased exercise tolerance (P0.05), left ventricular diastolic pressure decline rate of -dp/dt decreased (P0.05), left ventricular end diastolic pressure (resting about 12mmHg, about 16mmHg (load) P0.05), carotid artery pressure Ming Xian Zenggao (P0.05); left ventricular ejection fraction, fractional shortening, left ventricular systolic pressure rise rate (P0.05), but decreased ejection fraction was more than 50%, the systolic function is normal; myocardial cells of model rats decreased diastolic rate of -d1/dt decreased (P0.05), systolic rise rate decreased +d1/dt (P0.05) the maximum contraction amplitude, 50% time increased (P0.05); calcium transients in rat model of variable amplitude 50% time (P0.05), calcium (P0.05) fell 50% times increase, diastolic calcium elimination time constant (P0.05) and calcium (P0.05), calcium leakage increases, reduce the reserve (P0.05) calcium transport protein expression abnormal performance for CaMK II, PKA, NCX1, N/S (NCX1/SERCA2a) expression level increased (P0.05), PLB (S16), PLB (T17), the expression level of SERCA2a decreased (P0.05). In addition, rats in exercise performance based performance deficiency (P0.05) and fibrinogen content increased The main manifestation of blood stasis syndrome (P0.05). (2) of heart and lung qi and promoting blood circulation drug on weight, pressure load HFpEF big mouse myocardial fibrosis, effects of syndrome manifestations: 12 weeks of intervention compared with model group after the intervention group, standardized heart lung weight were decreased (P0.05); intervention group comparison of Yiqi Huoxue group 1:1, 2:1 group Yiqihuoxue standardized heart weight is better than blood group (P0.05), standardized lung weight improved Yiqi Huoxue group 2:1 was better than that of Yiqi group, Huoxue group, metoprolol group (P0.05), but 2:1 group and Yiqi Huoxue Yiqi Huoxue 1:1 between standardized heart lung weight (no difference P0.05); compared with the model group, Yiqihuoxue group 2:1 only can reduce the myocardial tissue of model rats with fibrosis score (P0.05); compared with the model group, Yiqi group, Yiqi Huoxue group 1:1 2:1 group, Yiqi Huoxue can improve Qi deficiency reflects the exhaustive distance, exhaustive time (P0.05); the intervention group the comparison of benefits Qi and blood group 2:1 exhaustive distance, exhaustive time is better than that of Yiqi group, Yiqi Huoxue group 1:1 (P0.05); only blood group, metoprolol group can reduce the fibrinogen content reflect the blood stasis syndrome (P0.05), Yiqi group, Yiqi Huoxue Yiqi Huoxue group 1:1, decreased fibrinogen content trend 2:1 group, but no statistical significance (P0.05); only blood group decreased the maximum platelet aggregation rate had significant difference (P0.05), there was no significant difference in the rest of the intervention group (PO.05), but showed a downward trend. (3) the intervention effect of Yiqi Huoxue drugs on negative pressure bearing left ventricular systolic and diastolic function of HFpEF rats after 12 weeks, the 2:1 of Yiqi Huoxue group compared with model group, can significantly improve the left ventricular ejection fraction (P0.05); compared with the model group, Yiqi group, metoprolol group after left ventricular diastolic wall thickness decreased (P0.05), live blood groups had no difference (P0.05), Yiqi Huoxue group 1:1 Yi. 2:1 can not only reduce the blood gas before and after the left ventricular diastolic wall thickness (P0.05), but also can reduce the ratio of E/e (P0.05), but no difference between the two groups (P0.05); the left ventricular diastolic function - Determination of suspended pipe resting state, compared with the model group, Yiqihuoxue group 2:1, 1:1 Yiqihuoxue group can significantly reduce left ventricular end diastolic pressure (P0.05), 2:1 group, Yiqi Huoxue can significantly increase the left ventricular diastolic pressure decline rate of -dp/dt (P0.05), and Yiqihuoxue group 2:1 improved left ventricular end diastolic pressure is better than that of group 1:1 (P0.05) of Supplementing Qi and activating blood circulation; dopamine load condition, compared with the model group, Qi blood group 2:1, Yiqi Huoxue 1:1 group can significantly reduce the left end of the Shi Shuzhang pressure, the increase of -dp/dt (P0.05); Yiqi Huoxue group 2:1 improved -dp/dt curative effect is better than that of group 1:1 (P0.05) Yiqi Huoxue Yiqi Huoxue drugs. (4) the pressure load on contraction of rat myocardial cells HFpEF Schwartz, calcium The intervention effect of steady state and calcium transport key protein: 12 weeks after operation, the myocardial contractile function compared with the model group, Yiqi group and Yiqi Huoxue group 1:1 group 2:1, time of Supplementing Qi and activating blood circulation can significantly shorten the maximum contraction amplitude of 50% myocardial cells (P0.05); intervention groups, Yiqi Huoxue group 1:1 time better than the 2:1 group of Yiqi Huoxue Yiqi group improve myocardial contractile amplitude of 50% (P0.05), Yiqi Huoxue group 1:1, there was no significant difference between the 2:1 group (P0.0.5); diastolic function: compared with the model group, the intervention group can improve the myocardial diastolic cell 50% (P0.05); intervention groups, better than the time Qi group Yiqi Huoxue group 2:1 improved diastolic myocardial cell 50% (P0.05) 2:1; Yiqi Huoxue group, Yiqi Huoxue group 1:1, the time is better than that of metoprolol group and Huoxue group improve the myocardial cell diastolic 50% (P0.05); Yiqi Huoxue group 1:1, there was no difference in 2:1 between groups ( P0.05); myocardial cell calcium release, compared with the model group, Huoxue group, metoprolol group can reduce myocardial cell calcium transient amplitude (P0.05), Yiqi group, Yiqi Huoxue group 1:1 2:1 group, Yiqi Huoxue can shorten the calcium transient amplitude of 50% time (P0.05), there is no difference between the three groups (P0.05); myocardial cell calcium intake back -- compared with the model group, Yiqi group and Yiqi Huoxue group 1:1 2:1 group, Yiqi Huoxue on calcium calcium down 50% time, eliminate time constant Tau value improvement (P0.05), there is no difference between the three groups (P0.05); blood group, dexmedetomidine sotalol group no statistical indexes the difference (P0.05)); calcium leakage and calcium reserves: compared with the model group, Yiqihuoxue group 2:1 only can reduce myocardial calcium leakage (P0.05); each group compared with the model group, calcium reserves were no difference (P0.05); the expression of calcium transport key protein: compared with the model group, each drug intervention can to reduce calcium Transport key protein CaMK II, and the expression level of NCX1/SERCA2a PKA (N/S) ratio (P0.05), only the expression of Yiqi Huoxue group 2:1 can reduce the expression of calcium release related protein RyR2 and increased calcium intake back related protein SERCA2a (P0.05)), Yiqi group, Yiqi Huoxue group 1:1 2:1 group, Yiqi Huoxue can reduce the level of the expression of NCX1 (P0.05), Yiqi group, Yiqi Huoxue group 2:1 can increase calcium shooting back related protein PLB (S16), PLB (T17) expression level (P0.05), metoprolol group can increase the expression level of PLB (T17) (PP0.05); intervention groups, Yiqi Huoxue group 2:1 improved CaMK II PKA, better than Qi group, improve the level of N/S is better than that of blood group, metoprolol group (P0.05)), the rest of the intervention group there was no significant difference between the 1. (P0.05). Conclusion: Yiqi group in improving exercise tolerance, left ventricular remodeling, left ventricular diastolic function and diastolic function of myocardial cells, and increased expression of calcium intake to PLB phosphorylation site The amount of.2. is better than that of the whole blood group, Yiqihuoxue prescription group treatment of diastolic heart failure curative effect is better than pure Yiqi, Huoxue Yiqi Huoxue Prescription group and metoprolol group control.3. Qi drug reuse diastolic dysfunction is more effective than conventional Yiqihuoxue prescription group.

【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R541.6

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