SERUM LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN PATIENTS WITH ANGINA PECTORIS AND ACUTE MYOCARDIAL INFARCTION

Objective. To determine whether serum vascular endothelial growth factor(VEGF)concentrations are altered in several kinds of coronary heart disease patients. Materials and methods. Using a VEGF enzyme-linked immunosorbent assay(ELISA), serum VEGF concentrations were determined in antecubital venous blood of 16 patients with stable angina pectoris(SAP), 16 with unstable angina pectoris(UAP) and 16 with acute myocardial infarction(AMI) before and after thrombolytic therapy, and of 16 age- and sex-matched healthy volunteers who used as controls. Results. The concentrations of serum VEGF in patients with SAP(9860±2699pg/ml) and UAP (10361±2489pg/ml) tended to be higher than those in control subjects(8044±2457pg/ml), but the differences did not reach statistical significance (P>005 for each). Before thrombolytic therapy, the concentrations of serum VEGF in patients with AMI (28592±12515pg/ml) were significantly higher than those in patients with SAP, UAP or control subjects (P<001,respectively), and correlated with synchronous serum creatine kinase (CK) and its MB isoenzyme (CK-MB) contents(r=0866,P<0001 and r=0948,P<0001;respectively). Three hours after thrombolysis, the concentrations of VEGF had fallen to 11157±3129pg/ml (P<001 vs. before thrombolytic therapy and P<005 vs.control subjects). Conclusion. The present study shows that serum concentrations of VEGF in patients with AMI are markedly elevated and that increased serum VEGF levels may be one of the most sensitive indexes in diagnosing AMI and judging reperfusion.

DYNAMIC CHANGES OF SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR LEVELS IN A RAT MYOCARDIAL INFARCTION MODEL

To investigate the dynamic changes of serum vascular endothelial growth factor(VEGF) levels in a rat model of acute myocardial infarction. Materials and methods.Eighty eight adult male Sprague Dawley rats weighing approximately 270 g were used in this study. Eighty rats were subjected to left coronary artery ligation, with 8 rats for each different duration of infarct. Eight sham operated animals in which the left coronary artery was surgically exposed without ligation were used as controls. Blood samples were drawn from the right atrium before (sham animals) and 1,3,6,12,24 h and 2,3,5,7,14 d after myocardial infarction. The concentrations of serum VEGF were measured by a sensitive enzyme linked immunosorbent assay with a rabbit polyclonal antibody specific for VEGF. Results. In the 8 control animals, the mean concentration of serum VEGF was 66.99±17.83 pg/ml. Six hours after myocardial infarction, the level of serum VEGF significantly increased to 125.68±28.07 pg/ml (P<0.01 vs. sham controls), and reached a peak (240.61±70.63 pg/ml. P<0.01 vs. sham animals) at 24 h after ligation and then decreased gradually over the remaining 2 weeks. However, the level remained significantly elevated for 14 d (107.64±30.13pg/ml, P<0.01 vs. sham controls). Conclusion. The present study shows that the levels of serum VEGF are markedly increased until 14 d in the rat model of acute myocardial infarction. The increased serum VEGF level may play an important role in the angiogenesis associated with myocardial infarction.

Changes of Serum Vascular Endothelial Growth Factor Concentrations in Acute Myoardial Infarction Rats and Patients

Objective To investigate thechanges of serum vascular endothelial growth factor (VEGF) concentration in a rat model of acute myocar-dial infarction (AMI) and in patients with AMI before and after thrombolytic therapy. Methods Eighty-eight male Sprague-Dawley rats were used and sixteen patients with AMI were studied in this study. AMI was produced by left coronary arterial ligation in 80 animals, and eight rats undergoing thoracotomy but not coronary ligation served as sham controls. The blood samples of rats were drawn from the right atrium before (0 hour, sham animals) and 1, 3, 6, 12 or 24 hours and 2, 3, 5, 7or 14 days after AMI (n = 8, respectively) . The blood samples of patients with AMI were collected from an antecubital vein before and 3 hours after thrombolytic therapy. Serum VEGF concentrations were measured by a sensitive and specific enzyme-linked immunosorbent assay (ELISA) . Results The mean serum VEGF concentration in 8 sham animals was 66. 99±17. 83pg/ml. Six hours after A-MI, the level of serum VEGF significantly increased to 125. 68±28. 07 pg/ml (P < 0. 01 vs Sham controls), and reached a peak (240. 61 ±70. 63 pg/ml, P < 0. 01 vs Sham controls) at 24 hours after ligation, and then decreased gradually over the remaining 2 weeks. However, the level remained significantly elevated for 14 days (107. 64±30. 13 pg/ml, P < 0. 01 vs Sham controls) . The basal serum level of VEGF in patients with AMI was significantly higher than that in 16healthy control subjects (285.92±125. 12 vs 80. 44 ±24. 57 pg/mL, P< 0.01), and correlated with synchronous serum creatine kinase (CK) and its MB isoenzyme (CK-MB) contents (r = 0.866, P< 0.001 and r = 0.948, P< 0.001; respectively) . Three hours after thrombolysis, the level of VEGF had fallen to 111. 57 ±31. 29 pg/mL (P <0. 01 vs Before thrombolytic therapy; P < 0. 05 vs control subjects) . Conclusion The present study shows that the concentrations of serum VEGF are markedly and permanently increased in the rat model of AMI and in patients with AMI. Serum VEGF concentrations may serve as a sensitive target in diagnosing AMI and judging reper-fusion.

Early Exercise Promotes Angiogenic Response in Mice Model of Myocardial Infarction

Objectives Little is known about the mechanism of exercise-induced angiogenic response in ischemic myocardium. This study was designed to investigate the effects of exercise training on expression of vascular endothelial growth factor and angiogenesis in infarcted heart. Methods Fifty male FVB mice were divided into three subgroups to test various responses to exercise, including time- dependent response of angiogenic factors to exercise training in intact heart (n=10) and infarcted heart (n= 10), as well as exercise-induced angiogenic response in heart with myocardial infarction (MI) (n=30). The mice in the exercise-training groups were allowed to exercise daily at 1 hour per day for 7 days. Results VEGF protein expression was up-regulated by exercise training in time dependent fashion in mice with MI. Angiogenesis was evident by increased myocardial mi- crovessels observed by PECAM-1 immunohistoc-hemi- cal staining in post-MI exercise group (16.5±3.4)/0.4 mm2 versus post-MI sedentary mice (10±2.1)/0.4 mm2 (P < 0.05). Cell proliferation assessment showed significantly higher (P < 0.05 ) number of BrdU positive cells in post MI mice in exercise group as opposed to sedentary post MI mice. 2%TTC staining disclosed a profound difference in the size of MI (18.25±2.93)% in exercise group vs sedentary group (29.26±7.64)% (P< 0.05). Conclusions Activation and up-regulation of VEGF in infarcted mice heart may contributes the angiogenic response to exercise training at the early stage of myocardial infarction. This underscores the impact of exercise on angiogenesis in post myocardial infarction setting.

Changes of Expressions of VEGF, bFGF, and Angiogenesis, and Effect of Benazepril, bFGF on Angiogenesis in Acute Myocardial Infarction Model of the Rabbits

Objective To explore the changes of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and angiogenesis, and the effects of bFGF, angiotensin converting enzyme inhibiter(ACEI) benazepril on the angiogenesis in acute myocardial infarction (AMI) model of rabbits, and to provide a probable evidence for the treatment of AMI. Methods AMI model was established by ligating anterior descending branch of coronary artery of Japan-Sino hybridization white rabbits. The postoperative rabbits were randomly divided into 6 groups and each group was treated with different drugs. Groups 1 and 2 were treated with normal saline (NS) for 28 and 14 days (d), group 3 and 4 with bFGF for 28 and 14 d, groups 5 with benazepril for 14 d, and group 6 with benazepril and bFGF for 14 d respectively. The rabbits were killed on the 14th or 28th d and their hearts were excised, sectioned and stained with HE, Masson trichrome to observe VEGF, bFGF and CD34 under a microscope, which were quantified with a computer-assisted morphometry. Results Compared with group 1, the granulation tissue of infarction zone (IZ) in group 2 freshened up, and the capillary density (CD) in IZ was increased (P=0.002). The CD in the IZ as well as VEGF and bFGF in groups 3 and 4 were increased respectively (P=0.011-0.037). In group 5 the changes of VEGF and bFGF were not found in the IZ and the border zone (BZ) while CD was significantly increased (35.4% and 25.6%, P=0.036 and 0.037). Compared with group 2, the CD in the IZ and BZ of group 6 was significantly increased (63.4% and 44.3% P=0.007 and 0.007), meanwhile VEGF and bFGF were increased. Compared with group 5, only VEGF was increased. Conclusion Intravenous bFGF may increase VEGF and bFGF significantly, thus promoting the angiogenesis in the IZ and BZ in cardiac infarction as VEGF and bFGF are the potent angiogenic growth factors. Benazepril may promote angiogenesis in the IZ and BZ in cardiac infarction, but its mechanism is irrelative to the expression of VEGF and bFGF. The combination of benazepril and bFGF may promote, to some extent, the expression of VEGF and bFGF, but their effect on angiogenesis has not been found.

Skeletal myoblast based delivery of angiogenic growth factors:a comparison between angiopoietin-1 and VEGF gene delivery for therapeutic angiogenesis in the heart

Objectives This study investigated the efficacy of human skeletal myoblasts (SkM) mediated either human vascular endothelial growth factor-165 (hVEGF165) or angiopoietin-1 (Ang-1) on vascular development and myocardial regional perfusion. Methods A porcine heart model of chronic infarction was created in 28 female swine by coronary artery ligation. The animals were randomized into: (1) group-1, DMEM injected (n=6), (2) group-2, Ad-null transduced SkM transplanted (n=6), (3) group-3, Ad-hVEGF165 transduced SkM transplanted (n=8), and (4) group-4, Ad-Ang-1 transduced SkM (n=8). Three weeks later, 5 ml DMEM containing 3×108 SkM carrying exogenous genes were intramyocardially injected into 20 sites in left ventricle in groups-2, -3 and -4. Animals in group-1 were injected 5 ml DMEM without cells. Animals were kept on 5 mg/kg cyclosporine per day for 6 weeks. Regional blood flow was measured using fluorescent microspheres. The heart was explanted at 2, 6 and 12 weeks after transplantation for histological studies. Results Histological examination showed survival of lac-z expressing myoblasts in host tissue. Capillary density based on Von Willebrand factor-VIII (vWF-VIII) at low power field (×100) was 57.13±11.85 in group-3 at 6 weeks and declined to 32.1±5.21 at 12 weeks, while it was 39.9±10.26 at 6 weeks and increased to 45.14±6.54 at 12 weeks in group-4. The mature blood vessel index was highest in group- 4 at 6 and 12 weeks after transplantation. The regional blood flow in the center and peri-infarct area was significantly increased in animals of groups-3 and -4. Conclusions SkM carrying either hVEGF165 or Ang-1 induced neovascularization with increased blood flow. Ang-1 overexpression resulted in mature and stable blood vessel formation and may be a more potent arteriogenic inducer for neovascularization.

Angiogenesis function of astragaloside Ⅳ in rats with myocardial infarction via PKD1-HDAC5-VEGF pathway

OBJECTⅣE This study aimed to investigate the role and mechanism of Astragaloside Ⅳ(AS-Ⅳ) in rats with myocardial infarction.METHODS The myocardial infarction model was established by ligation of the left anterior descending artery.The rats were randomly divided into sham,DMSO,model group,AS-Ⅳ and CID755673 groups.The rats were sacrificed 4 weeks later,and segmental heart samples were used for hematoxylin and eosin staining and masson staining.The expression of PKD1,HDAC5 and VEGF were analyzed using immunohistochemistry,reverse transcription poly.merase chain reaction and western blot.RESULTS Compared with the sham operation and DMSO groups,morphology of myocardium in model group was disordered,accompanied with necrotic myocar.dial cells and obvious collagen tissues.After treatment with AS-Ⅳ,the morphology of myocardium was obviously improved,and the number of new blood vessels increased significantly.However,after treatment with CID755673,the myocardial tissue of rats became disordered again,the necrotic cells increased,and some vessels closed.The expression levels of PKD1,HDAC5 and VEGF mRNA and protein in myocardial tissue of model group were significantly lower than the other four groups(P<0.05),whereas these levels in the AS-Ⅳ group were significantly higher than those in the other four groups(P<0.01).Additionally,the CID755673 group had significantly higher levels of PKD1,HDAC5 and VEGF mRNA and protein than the sham group,DMSO group and model group(P<0.05).CONCLUSION AS-Ⅳ may partly promote the angiogenesis of myocardial tissue in rats with myocardial infarction via the PKD1-HDAC5-VEGF pathway.

Huoxue Anxin Recipe(活血安心方)Promotes Myocardium Angiogenesis of Acute Myocardial Infarction Rats by Up-Regulating miR-210 and Vascular Endothelial Growth Factor

Objective： To investigate the microR NAs（miR NAs） expression profile of acute myocardial infarction（AMI） rats and the regulating effects of Huoxue Anxin Recipe（活血安心方, HAR） on angiogenesis-related miR NAs and genes. Methods： Forty-five Wistar rats were randomly assigned to 3 groups according to a random number table： sham, AMI, and AMI＋HAR groups（15 in each group）. AMI rats were established by ligation of the left descending coronary artery. HAR was intragastrically administered to rats of the AMI＋HAR group for successive 21 days since modeling, meanwhile the same volume of 0.9% normal saline was administered to rats of the sham and AMI groups. Doppler echocardiography was used for noninvasive cardiac function test. Hematoxylin and eosin staining was used to observe the histopathological change. miR NAs expression profile was detected by quantitative realtime polymerase chain reaction（qR T-PCR）. The mR NA and protein expressions of vascular endothelial growth factor（VEGF）, and a target gene of miR-210 was further detected by qR T-PCR and Western blot, respectively. The microvessels density of myocardium was evaluated by CD31 immunostaining. Results： Compared with the sham group, ejection fraction（EF） and fractional shortening（FS） values were decreased significantly in the AMI group（P〈0.01）, while the infarction area and the interstitial collagen deposition were increased obviously. As for the AMI＋HAR group, EF and FS values were increased significantly（P〈0.05 vs. AMI group）, and the infarction area was reduced and the interstitial collagen deposition were alleviated significantly. Total of 23 miR NAs in the AMI group expressed differently by at least 1.5 folds compared with those in the sham group; 5 miR NAs in the AMI＋HAR group expressed differently by at least 1.5 folds compared with those in the AMI group. Among them, miR-210 was low in the AMI group and high in the AMI＋HAR group. The relative mR NA and protein expressions of VEGF were decreased significantly in the AMI group（P〈0.05 vs. sham group）, and increased significantly in the AMI＋HAR group（P〈0.01 vs. AMI group）. CD31 expression area and optical intensity were decreased significantly in the AMI group（P〈0.05 vs. sham group）, and increased significantly in the AMI＋HAR group（P〈0.01 vs. AMI group）. Conclusions： HAR could reduce the infarction area, alleviate the interstitial fibrosis and improve the cardiac function of AMI rats. Those effects could be related to promoting myocardium angiogenesis of HAR by up-regulating miR-210 and VEGF.

Hypoxic preconditioning stimulates angiogenesis in ischemic penumbra after acute cerebral infarction

Previous studies have demonstrated the protective effect of hypoxic preconditioning on acute cerebral infarction, but the mechanisms underlying this protection remain unclear. To investigate the protective mechanisms of hypoxic preconditioning in relation to its effects on angiogenesis, we in- duced a photochemical model of cerebral infarction in an inbred line of mice （BALB/c）. Mice were then exposed to hypoxic preconditioning 30 minutes prior to model establishment. Results showed significantly increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra at 24 and 72 hours post infarction, mainly in neurons and vascular endothelial cells. Hypoxic preconditioning increased vascular endothelial growth factor and CD31 expression in the ischemic penumbra and the expression of vascular endothelial growth factor was positively related to that of CD31. Moreover, hypoxic preconditioning reduced the infarct volume and improved neu- rological function in mice. These findings indicate that the protective role of hypoxic preconditioning in acute cerebral infarction may possibly be due to an increase in expression of vascular endothelial growth factor and CD31 in the ischemic penumbra, which promoted angiogenesis.

Vascular endothelial growth factor expressing mesen-chymal stem cells improves cardiac function in chronic myocardial infarction in pigs

Transplantation of mesenchymal stem cells （MSCs） for myocardial reconstruction has shown promise in both animal models and human phase 1 clinical studies. Vascular endothelial growth factor （VEGF） is a strong therapeutic agent for treating ischaemia by inducing angiogenesis. The feasibility of ex vivo MSCs mediated gene transfer is documented. Matsumoto and colleagues have recently reported genetically engineered MSCs carrying VEGF165 delivery for revascularization in a model of acute myocardial infarction （MI）. The promising data from our laboratory in both angiogenesis and MSCs transplantation in cunicular heart model of acute MI have prompted us to attempt the combined and simultaneous application of the two strategies.

Hypoxia training attenuates left ventricular remodeling in rabbit with myocardial infarction

Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups： group SO （sham operated）, group MI （myocardial infarc-tion only） and group MI-HT （myocardial infarction plus hypoxia training）. Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber （having equivalent condition at an altitude of 4000 m, FiO214.9%） for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor （VEGF） in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI （130.27 ± 18.58 pg/mL,P〈 0.01） and MI-HT （181.93 ± 20.29 pg/mL,P〈 0.01） were significantly increased. Infarct size in Group MI-HT （29.67% ± 7.73%） was deceased remarkably, while its capillary density （816.0 ± 122.2/mm2） was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic （15.86 ± 1.09 mm,P〈 0.05） and end-systolic dimensions （12.10 ± 1.20 mm,P〈 0.01） significantly and im-proved left ventricular ejection fraction （54.39 ± 12.74 mm,P〈 0.05）.ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.

运动预处理对脑缺血再灌注大鼠脑缺血区VEGF/VEGFR2/Dock6信号通路的影响

目的:从VEGF/VEGFR2/Dock6信号途径探索运动预处理对脑缺血再灌注损伤大鼠缺血侧脑组织血管新生的影响。方法:采用随机数字表法将SD雄性大鼠分为假手术组、模型组和运动预处理组,每组18只。造模前,假手术组与模型组不给予任何处理,运动预处理组大鼠给予适应性跑步训练3d,电动跑台坡度为0°,速度10m/min,每天1次,每次20min。适应性训练结束后,运动预处理组给予为期3周的正式跑步训练,每周连续训练6d,休息1d,电动跑台坡度为0°,速度15m/min,30min/d。模型组和运动预处理组采用Koizumi栓线法加以改良制备大鼠大脑中动脉栓塞(MCAO)模型,假手术组仅切开皮肤,不插栓线。采用Zea-Longa评分和改良神经严重程度评分(mNSS)法进行神经功能缺损评估;TTC染色法检测脑梗死体积百分比,HE染色观察缺血侧大脑皮质组织形态学改变;免疫组化法观察缺血侧大脑皮质CD31表达水平;蛋白质免疫印迹测定VEGFA、VEGFR2、Dock6蛋白表达水平。结果:①Zea-Longa评分:再灌注麻醉清醒后,与假手术组相比,其余2组大鼠Zea-Longa评分均增高(P<0.01),且2组间Zea-Longa评分无显著性意义;再灌注72h后,与假手术组相比,模型组大鼠Zea-Longa评分显著增高(P<0.01);与模型组相比,运动预处理组大鼠Zea-Longa评分显著降低(P<0.05)。②mNSS评分:再灌注72h后,与假手术组相比,模型组大鼠mNSS评分显著增高(P<0.01);与模型组相比,运动预处理组大鼠mNSS评分显著降低。③TTC染色:与假手术相比,模型组脑梗死体积百分比增大(P<0.01);与模型组相比,运动预处理组脑梗死体积百分比相对减小(P<0.05)。④HE染色:与假手术组相比,模型组大鼠缺血侧大脑皮质出现显著病理学改变;与模型组相比,运动预处理组大鼠缺血侧大脑皮质病理学改变减轻。⑤CD31免疫组化:与假手术组相比,模型组大鼠缺血侧大脑皮质中CD31(P<0.01)显著升高;与模型组相比,运动预处理组大鼠缺血侧大脑皮质中CD31(P<0.01)进一步升高。⑥VEGF、VEGFR2、Dock6蛋白质免疫印迹:与假手术组相比,模型组大鼠缺血侧大脑皮质VEGF(P<0.05)、VEGFR2(P<0.05)、Dock6(P<0.01)蛋白表达含量升高;与模型组相比,运动预处理组大鼠缺血侧大脑皮质中VEGF(P<0.05)、VEGFR2(P<0.05)、Dock6(P<0.01)蛋白表达含量进一步升高。结论:运动预处理可有效促进脑缺血后血管新生,减轻脑缺血再灌注以后的神经功能缺损表现,这一作用可能与其激活VEGF/VEGFR2/Dock6信号途径有关。

白术内酯I调节HIF-1α/VEGF信号通路对急性心肌梗死大鼠心肌损伤的影响

目的:探讨白术内酯I(Atr-I)调节缺氧诱导因子1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的影响。方法:大鼠分为对照组、AMI组、Atr-I组、阿司匹林组、BAY87-2243组、Atr-I+BAY87-2243组,每组18只。除对照组外,其他组大鼠均采用结扎冠脉左前降支根部的方式构建AMI模型,建模1h后,开始处理,给药1次/d,持续7d。超声心动图监测左室短轴缩短率(FS)、左室射血分数(LVEF)的变化;2,3,5-三苯基氯化四氮唑(TTC)染色检测大鼠心肌梗死面积百分数;HE染色检测左心室心肌组织病理学变化;TUNEL染色检测心肌细胞凋亡;ELISA检测大鼠左心室心肌组织中肌红蛋白(Mb)、乳酸脱氢酶(LDH)、肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β含量;Western blot检测大鼠心肌组织匀浆中HIF-1α、VEGF蛋白表达。结果:与对照组相比,AMI组大鼠心肌损伤明显,FS、LVEF及HIF-1α、VEGF蛋白表达降低,心肌梗死面积百分数、Mb、LDH、TNF-α、IL-1β含量升高(P<0.05);与AMI组相比,Atr-I组、阿司匹林组大鼠心肌损伤有所改善,FS、LVEF及HIF-1α、VEGF蛋白表达升高,心肌梗死面积百分数、Mb、LDH、TNF-α、IL-1β含量降低,BAY87-2243组对应指标变化趋势与上述相反(P<0.05);与Atr-I组相比,Atr-I+BAY87-2243组大鼠心肌损伤加剧,FS、LVEF及HIF-1α、VEGF蛋白表达降低,心肌梗死面积百分数、Mb、LDH、TNF-α、IL-1β含量升高(P<0.05)。结论:Atr-I减轻AMI大鼠心肌损伤可能与激活HIF-1α/VEGF信号通路有关。

急性心肌梗死经皮冠状动脉介入治疗预后不良因素的研究现状

急性心肌梗死(AMI)是因冠状动脉急性闭塞、血流中断引起的局部心肌缺血性坏死,主要临床表现为持续性胸骨后疼痛、休克、心律失常和心力衰竭等,并伴有血清心肌酶增高以及心电图改变,病死率较高。临床最常见的AMI手术治疗方法为经皮冠状动脉介入治疗(PCI),影响PCI手术预后效果的因素较多,主要包括血清肌酐水平、心理状态、营养不良、合并糖尿病和血清肌钙蛋白T水平、复流发生率、血管内皮生长因子等。近年来,提升AMI患者PCI手术预后的方法一直是临床AMI治疗的研究重点。

VEGF-expressing Bone Marrow Mesenchymal Stem Cells Transplantation Improved Heart Function of Myocardial Infarct Rabbits

Objectives To treat myocardial infarction with MSCs transplantation combined with VEGF gene therapy in rabbits and to study its mechanisms. Methods Forty-eight rabbits were randomly divided into MI group （n=12）, MSCs group （n=12）, VEGF group （n=12）, MSCs＋VEGF group （M＋V group, n=12）. Rabbit myocardial infarction models were founded by the ligation of left anterior descending artery. 107 MSCs were injected into the infarct-zone in four sites 2 weeks later in MSCs and M＋ V group, phVEGF gene were injected in infarct-zone in VEGF group and MSCs transfected with phVEGF gene were injected in M＋V group. Heart function including LVEDP, LVSP, LVDP, -dp/dtmax, ＋dp/dtmax, were measured in vivo. The hearts were harvested at 4 weeks after transplantation and sectioned for HE stain, immunohistochemical stain of BrdU and VIII factor antigen. Results The left ventricular hemodynamics parameters showed that heart function were improved more in M＋V group than MSCs group, MI group and VEGF group. The numbers of BrdU positive cells in M＋ V group（61±8）were more than in MSCs group （44±8, P 〈 0.01）. The numbers of vessels in infarcted zone were more in M＋V group （49±8） than in MSCs group （33±6, P 〈 0.01）,VEGF group（30±8, P 〈 0.01）and Mlgroup （18±4, P〈0.01）. Conclusions VEGF-expressing MSCs transplantation could improve heart function after myocardial infarction, and they were more effective than sole MSCs transplantation. Keeping more MSCs survival and ameliorating the blood supply of infarct-zone might be involved in the mechanisms.

冠通方对急性心肌梗死大鼠心肌血管新生的影响

目的 观察冠通方对急性心肌梗死(AMI)大鼠缺血心肌的保护作用及对血管新生的影响。方法 将SD大鼠随机分为空白对照组、模型组、麝香通心滴丸组和冠通方组,除对照组外,其余各组大鼠均采用左冠状动脉前降支结扎法建立AMI模型,对照组只穿线不结扎。造模成功后,麝香通心滴丸组每日予麝香通心滴丸灌胃,冠通方组每日予冠通方灌胃,其余各组大鼠予等体积生理盐水灌胃,连续14 d。称大鼠体质量及心脏质量,计算心脏/体质量比;HE染色法评价大鼠心肌组织损伤程度;免疫荧光法测定大鼠心梗边缘区CD34阳性表达及计数微血管数目(MVC);免疫组化测定大鼠心肌组织血管内皮生长因子(VEGF)蛋白表达。结果 与空白对照组比较,模型组心脏/体质量比明显增加(P <0.01);模型组HE染色显示心肌细胞结构紊乱,细胞碎裂、坏死,间质充血和炎性细胞浸润现象;免疫荧光检测示心肌组织CD34表达及MVC升高(P <0.01);免疫组化检测示心肌组织VEGF蛋白表达增加(P <0.01)。与模型组比较,冠通方组心脏/体质量比明显下降(P <0.01);CD34表达及MVC显著升高(P <0.01);VEGF蛋白表达显著增加(P <0.01)。结论 冠通方可通过促进缺血区血管新生来减轻心肌细胞损伤,保护受损心肌。

远程肢体缺血预适应通过上调血管内皮生长因子表达促进急性心肌梗死患者侧支循环形成

目的探讨远程肢体缺血预适应(RLIP)对急性ST段抬高型心肌梗死(STEMI)择期经皮冠状动脉介入治疗(PCI)患者血浆血管内皮生长因子(VEGF)及冠状动脉侧支循环(CCC)的影响。方法选择2019年3月至2020年9月于粤北人民医院就诊因错过再灌注时间窗择期行PCI的STEMI患者90例。随机分为缺血预适应组(n=45,行远程肢体缺血预适应)和对照组(n=45,术前不行远程缺血训练)。所有患者分别于入院时及PCI当日采集静脉血,通过ELISA方法定量血浆VEGF浓度。同时记录及计算两组患者PCI术中侧支循环发生率及级别水平(0~3级)。根据术中侧支循环级别重新分组,以侧支循环2~3级为侧支循环良好组,0~1级为侧支循环不良组,分别检测及统计侧支循环良好组及不良组的VEGF水平,探讨其与冠状动脉(冠脉)侧支循环形成的关系。结果术中发现缺血预适应组侧支循环良好的患者数量远多于对照组(19例vs.7例,P=0.016)。按侧支循环良好与否重新分组,测得两组(侧支循环良好组及侧支循环不良组)入院时VEGF浓度无明显差别[(142.42±22.24)pg/ml vs.(145.37±37.65)pg/ml,P=0.563],而手术当天测得侧支循环良好组血浆VEGF浓度较侧支循环不良组高[(236.26±28.78)pg/ml vs.(154.31±34.96)pg/ml,P=0.002],差异有统计学意义。结论远程肢体缺血预适应可促进STEMI择期PCI患者冠脉侧支循环的形成,其机制可能与远程肢体缺血预适应可上调VEGF表达有关。

促心脏淋巴管生成与基于抗心肌纤维化治疗心血管疾病研究进展

淋巴管是一种低压、盲端管状结构,在维持组织液体稳态、免疫细胞运输以及膳食脂质摄取和运输中发挥着重要作用,并参与免疫反应。淋巴管生成的抑制参与了缺血性损伤或压力超负荷后的心脏水肿和心脏重构。新的研究表明,促进淋巴管的生长、重塑和功能发挥可以在一些病理生理条件下减少炎症和减轻疾病严重程度。因此,促进淋巴管生成在心血管疾病中可能成为一种很有前途的治疗方法。当淋巴管重塑不足或适应不良时,它会导致淋巴运输功能障碍,导致慢性间质水肿和炎症,从而触发间质纤维化的发展。本文主要综述了心脏淋巴管在心血管疾病中的作用,介绍了心脏淋巴转运不良与心肌纤维化的相关性以及淋巴管生成在心血管疾病中的潜在益处。以期为心血管疾病的诊治提供新的思路和靶点。

针刺阳陵泉穴对缺血性脑卒中大鼠神经功能及血管再生因子Nogo-A、VEGF表达影响

目的 观察针刺阳陵泉穴对缺血性脑卒中大鼠神经功能及血管再生因子轴突生长抑制因子(Nogo-A)、血管内皮生长因子(VEGF)表达的影响,探讨针刺促进脑重塑的作用机制。方法 将雄性SD大鼠随机分为假手术组、模型组、针刺组,采用改良线栓法制备大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)大鼠模型,其中假手术组与模型组无治疗措施,针刺组给予电针双侧阳陵泉穴治疗14 d,各组基于造模术后1 d、术后14 d分为2个亚组,每个亚组各8只,采用TTC染色法检测造模情况,观察各组在不同时点神经功能缺损评分变化,通过ELISA法、RT-PCR技术、免疫组化法分别检测各组大鼠血清、脑组织中Nogo-A、VEGF表达水平。结果 与模型组比较,治疗14 d后针刺组大鼠神经功能缺损评分有所降低(P<0.01);针刺组能明显下调MCAO大鼠血清及脑组织中Nogo-A表达(P<0.05),同时可显著上调VEGF表达(P<0.05)。结论 针刺阳陵泉穴可改善MCAO大鼠神经功能缺损,且其机制可能与抑制Nogo-A表达、上调VEGF表达、促进血管再生有关。

中药防治心肌梗死的促血管新生机制研究进展

心肌梗死是世界范围内最常见的死亡原因,在我国是一个重大的社会公共卫生负担,促进缺血区域血管新生、建立侧支循环供血是治疗心肌梗死的重要措施。现代研究发现,多种中药如黄芪、三七、红景天、当归、丹参、葛根等能通过刺激血管内皮细胞生长因子(VEGF)、缺氧诱导因子(HIF)、成纤维细胞生长因子(FGF)、肝细胞生长因子(HGF)等多个血管新生相关细胞因子,调控缺氧诱导因子-1α/血管内皮生长因子信号通路(HIF-1α-VEGF)、血管生成素/血管生成素受体-2(Ang-Tie2)等多条信号通路,发挥促血管新生作用。对相关内容进行综述,可为防治心肌梗死的临床研究和新药开发提供参考。参考文献44篇。