过表达肌浆网钙ATP酶治疗实验性慢性缺血性心力衰竭

Objective Chronic myocardial ischemia (CMI) has become the most importat cause of heart failure (HF) all over the world. The aim of the current study was to investigate the effects of Sarcoendoplasmic reticulum calcium ATPaee 2a (SERCA2a) gene transfer on cardiac function and endoplasmic reticulum stress (ERS) associated myocardial apoptosis in a minipig HF animal model induced by CMI. Methods HF was induced in minipigs by implantation of ameroid constrictor in the initial segment of left anterior descending (LAD) branch of coronary artery. After confirmation of myocardial perfusion defects and cardiac function impairment by myocardial perfusion imaging and echocardiography, animals were divided into 4 groups (n =4 each): HF group, HF + enhanced green fluorescent protein (EGFP) group,HF + SERCA2a group, and shamed animals as control group. A total amount of 1×1012 v.g. Of rAAV1EGFP or rAAV1-SERCA2a were injected intramyocardially to each animal of HF + EGFP and HF +SERCA2a groups. Sixty days after gene transfer, protein level and activity of SERCA2a were examined,cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. Apoptotic index of the ischemic myocardium, protein levels of ER stress marker glucose regulated protein 78 ( GRP 78) and ER stress specific apoptotic marker caspase-12 were also assayed. Results At the study end,echocardiographic and hemodynamic measurements indicated a significant improvement of both cardiac systolic and diastolic function in HF + SERCA2a group compared with HF/HF + EGFP groups [LVEF (60.2±8.6)%vs (44.2±7.1)% and (46.8±6.7)%, Ev/Ay 1.28±0.24 vs 0.77 ±0.17 and 0.80±0.21, +dp/dtmax(2713.9 ±434.0) mm Hg/s ( 1 mm Hg =0.133 kPa) vs (1892.3 ±434.2) mm Hg/s and (1931.2±397.4)mm Hg/s, -dp/dtmax (1422.1±334.4) mm Hg/s vs (848.3±308.3) mm Hg/s and (849.5±278.3)mm Hg/s, P＜0.05], along with increase in both SERCA2a protein level (1.13±0.26 vs 0.73 ±0.17 and 0.64±0.18, P＜0.05) and activity [(16.2±5.5) IU/ml vs (7.9±3.1) IU/ml and (7.5 ±2.8)IU/ml, P ＜0.05] compared with HF/HF + EGFP groups. Serum concentrations of inflammatory factor tumor necrotic factor α [(382.3±114.4) ng/L vs (732.3±201.4) ng/L and (689.8±192 5) ng/L, P＜0. 05], neural-hormonal factors brain natriuretic peptide [(142.6±45.3) ng/L vs (422.3±113.6) ng/L and(393.7 ±103.3)ng/L, P＜0.01], endothelin-1 [(111.4 ±37.5)ng/L vs (193.5 ±54.3)ng/L and (201.0±72.1)ng/L,P＜0.05] and angiotensin Ⅱ[(189.7±65.2)μg/L vs (538.3 ± 135.2) μg/L and ( 525.5±144.1)μg/L, P＜0.01] were also significantly decreased in HF + SERCA2a group compared with HF/HF + EGFP groups. The apoptotic index [(12.71±4.11)% vs(23.22±7.23) % and (24.31±6.38)%, P＜0.05], protein levels of GRP78 (1.27±0.33 vs 3.23±1.14 and 4.18±1.13, P＜0.05)and protein level ratios of cleaved caspase-12 to total caspase-12[(4.62±1.93)% vs (9.71±2.70)% and (10.14±2.81)%, P＜0.05] were also significantly reduced in the ischemic myocardium of HF+SERCA2a group compared with the HF/HF + EGFP groups. Conclusion Overexpression of SERCA2a significantly improved cardiac systolic and diastolic function in this HF model partly through attenuation of ER stress related myocardial apoptosis, suggesting its therapeutic potential for CM1 related heart failure.     

脉搏波速度临床应用价值及研究进展

血管疾病是累及全身的一组病变,它包括冠状动脉疾病、脑血管疾病、肾血管疾病和外周血管疾病等,为了从根本上降低上述疾病导致的致残、致死的严重后果,血管病变早期识别极为重要,特别是在表现健康的人群中高效准确地识别已患亚临床动脉粥样硬化的个体,是预防决策的重点,也是早期采取生活方式干预的依据.     

复合型木脂素类化合物的研究进展

目的：对近十年来有关复合型木脂素的研究进行综述。方法：通过查阅1999—2010年的相关文献,对新发现的复合型木脂素从其植物分布、结构类型、生物活性等方面的研究进行总结。结果：复合型木脂素主要包括木脂素与黄酮、生物碱、香豆素、萜类的复合体,具有抗炎、抗氧化、细胞毒性等活性。结论：复合型木脂素结构新颖,值得进一步的研究和开发。     

过表达肌浆网钙ATP酶治疗实验性慢性缺血性心力衰竭

Objective Chronic myocardial ischemia (CMI) has become the most importat cause of heart failure (HF) all over the world. The aim of the current study was to investigate the effects of Sarcoendoplasmic reticulum calcium ATPaee 2a (SERCA2a) gene transfer on cardiac function and endoplasmic reticulum stress (ERS) associated myocardial apoptosis in a minipig HF animal model induced by CMI. Methods HF was induced in minipigs by implantation of ameroid constrictor in the initial segment of left anterior descending (LAD) branch of coronary artery. After confirmation of myocardial perfusion defects and cardiac function impairment by myocardial perfusion imaging and echocardiography, animals were divided into 4 groups (n =4 each): HF group, HF + enhanced green fluorescent protein (EGFP) group,HF + SERCA2a group, and shamed animals as control group. A total amount of 1×1012 v.g. Of rAAV1EGFP or rAAV1-SERCA2a were injected intramyocardially to each animal of HF + EGFP and HF +SERCA2a groups. Sixty days after gene transfer, protein level and activity of SERCA2a were examined,cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. Apoptotic index of the ischemic myocardium, protein levels of ER stress marker glucose regulated protein 78 ( GRP 78) and ER stress specific apoptotic marker caspase-12 were also assayed. Results At the study end,echocardiographic and hemodynamic measurements indicated a significant improvement of both cardiac systolic and diastolic function in HF + SERCA2a group compared with HF/HF + EGFP groups [LVEF (60.2±8.6)%vs (44.2±7.1)% and (46.8±6.7)%, Ev/Ay 1.28±0.24 vs 0.77 ±0.17 and 0.80±0.21, +dp/dtmax(2713.9 ±434.0) mm Hg/s ( 1 mm Hg =0.133 kPa) vs (1892.3 ±434.2) mm Hg/s and (1931.2±397.4)mm Hg/s, -dp/dtmax (1422.1±334.4) mm Hg/s vs (848.3±308.3) mm Hg/s and (849.5±278.3)mm Hg/s, P＜0.05], along with increase in both SERCA2a protein level (1.13±0.26 vs 0.73 ±0.17 and 0.64±0.18, P＜0.05) and activity [(16.2±5.5) IU/ml vs (7.9±3.1) IU/ml and (7.5 ±2.8)IU/ml, P ＜0.05] compared with HF/HF + EGFP groups. Serum concentrations of inflammatory factor tumor necrotic factor α [(382.3±114.4) ng/L vs (732.3±201.4) ng/L and (689.8±192 5) ng/L, P＜0. 05], neural-hormonal factors brain natriuretic peptide [(142.6±45.3) ng/L vs (422.3±113.6) ng/L and(393.7 ±103.3)ng/L, P＜0.01], endothelin-1 [(111.4 ±37.5)ng/L vs (193.5 ±54.3)ng/L and (201.0±72.1)ng/L,P＜0.05] and angiotensin Ⅱ[(189.7±65.2)μg/L vs (538.3 ± 135.2) μg/L and ( 525.5±144.1)μg/L, P＜0.01] were also significantly decreased in HF + SERCA2a group compared with HF/HF + EGFP groups. The apoptotic index [(12.71±4.11)% vs(23.22±7.23) % and (24.31±6.38)%, P＜0.05], protein levels of GRP78 (1.27±0.33 vs 3.23±1.14 and 4.18±1.13, P＜0.05)and protein level ratios of cleaved caspase-12 to total caspase-12[(4.62±1.93)% vs (9.71±2.70)% and (10.14±2.81)%, P＜0.05] were also significantly reduced in the ischemic myocardium of HF+SERCA2a group compared with the HF/HF + EGFP groups. Conclusion Overexpression of SERCA2a significantly improved cardiac systolic and diastolic function in this HF model partly through attenuation of ER stress related myocardial apoptosis, suggesting its therapeutic potential for CM1 related heart failure.     

小型猪慢性心肌缺血心衰模型的建立与评价

目的:建立慢性心肌缺血致心力衰竭的动物模型。方法: 小型猪18只,随机分为假手术组（n=4）和模型组（n=14）,模型组开胸于前降支近端放置ameroid缩窄环,假手术组分离前降支不套环。术后4周,行单光子发射计算机断层成像(SPECT)观察心脏灌注情况。应用无创超声心动图、有创血流动力学检查并评价心脏的舒缩功能。应用放射免疫测定法检测血清脑钠尿肽(BNP)、心肌肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、内皮素1(ET-1)和血管紧张素Ⅱ(AngⅡ)等浓度的变化。结果: 模型组死亡2只,其余16只动物手术顺利完成。SPECT显示,模型组前降支供血区域心肌存在严重灌注障碍;假手术组无明显灌注缺损。超声心动图和血流动力学检查提示,模型组心脏的收缩和舒张功能严重受损,并发生心腔扩张,同时血清BNP的水平增高,心肌损伤标记物、炎性因子和神经体液因子的浓度也明显增高;假手术组上述参数均无显著改变。结论: 在猪的前降支近端放置ameroid缩窄环是制作慢性心肌缺血心力衰竭动物模型的有效方法。     

脉搏波速度临床应用价值及研究进展

血管疾病是累及全身的一组病变,它包括冠状动脉疾病、脑血管疾病、肾血管疾病和外周血管疾病等,为了从根本上降低上述疾病导致的致残、致死的严重后果,血管病变早期识别极为重要,特别是在表现健康的人群中高效准确地识别已患亚临床动脉粥样硬化的个体,是预防决策的重点,也是早期采取生活方式干预的依据。脉搏波速度(PWV)是公认的评价动脉弹性的经典指标,是一种简单无创可靠重复性好     

心肌肌浆网Ca2+-ATP酶过表达对慢性缺血性心力衰竭小型猪心功能的改善作用

目的 研究心肌肌浆网Ca<'2+>-ATP酶(SERCA2a)基因过表达对慢性缺血性心力衰竭(HF)小型猪心功能的改善作用.方法 使用Ameroid缩窄环束扎小型猪前降支起始段,4周后行超声心动和血流动力学检查确认心功能下降,放免法测定血清炎性因子(TNF-a、IL-6)和神经体液因子(BNP、AngⅡ、ET-1)的变...