腺病毒介导的血管内皮生长因子165对扩张型心肌病大鼠心功能的影响

Effects of Adenovirus-mediated Vascular Endothelial Growth Factor 165 Gene on Cardiac Function in SD Rats of Dilated Cardiomyopathy Induced by Adriamycin via Pericardial Cavity

目的:观察经心包腔注射腺病毒介导的血管内皮生长因子165基因(Ad-VEGF 165)对扩张型心肌病(DCM)大鼠心功能的影响并探讨其作用机制。方法:35只雌性SD大鼠腹腔注射多柔比星建立扩张型心肌病模型,随机分为2组:VEGF组(18只)心包腔内注射0.1 mL Ad-VEGF 165 1.0×109pfu;DCM组(17只)注射生理盐水。比较4周后大鼠左室收缩末期容积(LVES)、舒张末期容积(LVED)、左室收缩末期内径(SD)、左室舒张末期内径(DD)、左室内径缩短率(FS)、左室射血分数(LVEF)和体重(BW)、心率(HR)的变化,观察大鼠心肌组织改变情况,ELISA法测定血清APO-1/Fas含量。结果:VEGF组BW、LVEF、HR、FS较DCM组明显增加(P<0.01);LVES、LVED、SD、DD均明显降低(P<0.05),APO-1/Fas水平较DCM组下降(P<0.01);注射VEGF后大鼠BW、LVEF、HR、FS较注射前明显增加(P<0.01);而LVES、LVED、SD、DD则明显降低(P<0.05),大鼠的心肌病变减轻。结论:心包注射Ad-VEGF165基因可改善DCM鼠心功能,降低其死亡率,有利于心肌细胞的存活,其机制可能与减少心肌细胞凋亡有关。

Objective To study the effects of adenovirus - mediated vascular endothelial growth factor 165 gene on cardiac function in SD rat model of dilated cardiomyopathy （ DCM ） induced by adriamycin injection via pericardial cavity and explore its possible mechanism. Methods SD rat model of DCM was established at a dose of 2mg/kg once a week by adriamycin intraperitoneally injected and were randomly divided into experimental group and control group. Rats in experimental group received 1.0×10^9 pfu Ad -VEGF 165 injections via pericardial cavity（ VEGF group） ,while 0.9 % sodium choloride was injected into rats in control group（ DCM group）. The pericardium was pretreated by injecting a mixture of collagenase （250U）and hyaluronidase （600U）. In order to evaluate the effects of Ad - VEGF 165 gene on SD rat models of DCM, transthoracic echocardiography was performed in VEGF group at 4 weeks after treatment with Ad - VEGF 165 gene injection to measure left ventricular dimensions and calculate ejection fraction. At 2 weeks after treatment, left ventricular slices of animal model were processed for histological staining and the concentration of plasma APO - 1/Fas was examined with ELISA. Results Compared with the DCM group, the left ventricular ejection fraction （ LVEF ）, body weight （ BW ） and heart rate （HR） were increased significantly （ P 〈 0.01 ） , the left ventricular end diastolic （ LVED ） , diastolic dimension （ DD ） and systolic dimension（SD） were smaller,the fraction shortening（FS） was larger than that in DCM group（ P 〈 0.05 ） ,whereas the left ventricular end systolic（LVES） in DCM rats of Ad - VEGF 165 gene injection were decreased markedly（ P 〈 0.01 ） by transthoracic echocardiography measurement. Compared with the DCM group, the LVES and SD in Adriamycin- DCM rats with Ad - VEGF 165 injection were decreased significandy（ P 〈 0.01 ） ,the LVED and DD were smaller and FS was lar-ger（ P 〈 0. 05 ） ,the LVEF and HR were increased（ P 〈 0.01 ）. The levels of plasma APO - 1/Fas were lower than that in DCM group. Conclusions Ad - VEGF 165 gene injection via pericardial cavity has therapeutic effect on animal model of dilated cardiomyopathy and is benificial to the survival of myocytes ,which may relate to inhibiting myocytes apoptosis and thus offer a novel therpeutic strategy.