【作者】 黄荣杰；

【导师】 刘唐威； 伍伟锋；

【作者基本信息】 广西医科大学 ， 心血管内科， 2003， 硕士

【摘要】 目的 建立呋喃唑酮扩张型心肌病(furazolidone-induced dilated cardiomyopathy,Fz-DCM)大鼠模型，探讨Fz-DCM大鼠心室重构的特征。 方法 Wistar大鼠60只，雌雄各半，随机分为DCM模型组(DCM组)和正常对照组(NC组)，再根据饲养的时间每个组中又分为4周、8周和12周三个亚组，每个亚组10只大鼠。DCM组在饮水中加呋喃唑酮饲养，而NC组在饮水中不添加呋喃唑酮饲养。分三批在饲养4周、8周和12周时，应用超声心动图检测各亚组大鼠左室舒张期末内径(LVED)、左室收缩期末内径(LVES)、左室内径缩短率(FS)及左室射血分数(LVEF)；有创导管测主动脉压和右房压力；大体病理检测大鼠的左室内径和左室游离壁的厚度；大鼠心室肌组织HE染色观察组织病理改变，VG染色检测心肌胶原纤维及胶原容积分数(CVF)。 结果 ①DCM组呋喃唑酮饲养12周后诱发DCM模型总成功率为66.6％(20／30)，其中4周、8周和12周亚组的Fz-DCM大鼠数分别是8只、6只和6只。②与NC组相应亚组相比，DCM组4w、lzw亚组的大鼠心脏的LVED(cm)明显增大(0.59士O.41VS0 .52士0.29，0.65士0.02 VS 0.63士0.46，均夕<0.01)，且LVES(cm)也明显增大(0.35士0.04 VS 0.29士0.03，0.46士0.05 VS 0.35士0.29，均p<0.01)，但两组中sw亚组的LVED、LVEs均无明显差异(均p>.05)。③与NC组相应亚组相比，DCM组各亚组的FS(%)均明显下降(38.46士3.92 vs 46.71士3.50，夕<0.01，29.62士4 .09 VS 36.46士2.56P<0.05，30.97士4.97 VS 44.44士3.26，夕<0.01)，且LVEF(%)也明显减低(75.71士3.62 VS 83.20士3.34，62.76士6.12 VS 71.46士1.15，63.82士7.24 VS 80.96士3.16，均p<0 .01)。④与Nc组相应亚组相比，DcM组各亚组的右房压(mmHg)均明显增高(一3.90士4.91 VS4‘20士3.27，19.67士2.94vs6.70士2.95，11.25士3.28 VS 5.70士2.00，均夕<0.01)，而两组的主动脉压无明显差异(均p>.05)。⑤与Nc组相应亚组相比，DcM组各亚组的左室内径(mm)明显增大(4 .25士0.60 vs 3.08士0.92P<0 .05，4.67士0.61 VS 3.70士0.59，4.37士O，64 VS 3.45士0.37均p<0.01);而且8周和12周亚组的左室游离壁厚度(mm)明显变薄(2.58士0.38 VS 4.00士0.58尸<0.01，3.13士O，23 VS 3.55士0.50尸<0.05)。⑥与NC组相应亚组相比，DCM组12周亚组的心脏重量/体重比值(mg/g)明显增加(2.95士0.15 vs 2.76士0.10尸<0 .05)，但各亚组的左室重量/全心重量比值(m留mg)无明显差 一2-异(均p>0.05)。⑦DcM组大鼠心室肌组织HE染色观察见心肌细胞肥大，胞浆灶性溶解，有不同程度的颗粒变性与空泡变性，细胞核增大、分裂、畸形，细胞间隙增宽。⑧v一G染色见DCM组中8周和12周亚组大鼠心肌组织间质胶原纤维明显增多，CVF(%)较NC组相应亚组均明显增加(18.96士4.78 VS 11.89士3.69，21.31士4.55 vs 12.r5土2.59，均尸<0.01)，但两组中的4周亚组的CVF比较无明显差异(p>.05)。结论应用吠喃哇酮能成功诱发DCM大鼠模型。Fz一DCM大鼠具有左室扩大、心室壁变薄，心肌细胞肥大、变性，间质纤维组织增生等病理改变，并且左室收缩功能下降，提示Fz一DCM大鼠模型能反映扩张型心肌病的病理生理特征。更多还原

【Abstract】 Objective TO create the rat model of furazolidone-induced dilated cardiomyopathy (Fz-DCM) and explore the characterization of ventricular remodeling in Fz-DCMMethods sixty wistar rats were randomized into the DCM group and the control group, and then each group was divided into three subgroups bas on the feeding time, netmely the four-week, eight-week and twelve-week subgroup wich has ten rats equally. Each subgroup of the DCM group was fed with furazolidone for four weeks, eight weeks and twelve weeks respectively, the control group was fed regulately, and then left ventricular dimension and cardiac funtion were detected by echocardiogram. Aortic and right atrial pressure were measured by invasive catheter. Left ventricular interior diameter and the thickness of left ventricular free wall were measured after the rats were killed. Myocardial collagen network remodeling was observed by Van Gieson stain and collagen volumefraction (CVF) was caculated by pathalogical imagine analysis system. Result (1)The total incidence rate of DCM was 66.6%(20/30) inDCM group fed with furazolidone,among them the quantity of the rats diagnosised as DCM by histopathology was 8(8/10),6(6/10) and 6(6/10) in the four-week , eight-week and twelve-week subgroup respectively.(2)The left ventricular end-diastolic diameter (LVED) and left ventricular end-systolic diameter(LVES) in the four-week and eigh-week subgroups of the DCM group were larger than those in the corresponding subgroups of the cntrol group[LVED(cm): 0.59 ± 0.41VS 0.52 ± 0.29 p<0.01l, 0.68 ± 0.02 VS 0.63 ± 0.46 p<0.01 ; LVES(cm): 0.35±0.04 VS 0.29±0.03 p<0.01, 0.46 ± 0.05 VS 0.35 ± 0.29 p<0.01],however,there were no differences between the two eighth-week subgroups in LVED and LVES ( all p>0.05) . (3) Compared with the corresponding subgroups of control group ,the fraction shortening[FS(%)] in all subgroups of the DCM group was decreased significantly (38.46±3.92 VS 46.71 ± 3.50, p<0.01, 29.62 ± 4.09 VS 36.46 ± 2.56 P<0.05 , 30.97 ± 4.97 VS 44.44 ± 3.26 p<0.01 ),moreover, the left ventricular ejection fraction[LVEF(%)] in all subgroups of the DCM group was decreased significantly. (75.71 ± 3.62 VS 83.20±3.34 , 62.76 ± 6.12 VS 71.46 ± 1.15, 63.82±7.24 VS 80.96 ± 3.16 all p<0.01). (4) The right atrial pressure(mmHg) in all subgroups of the DCM group increased more significantly than those of the corresponding subgroups of the cntrol group (13.90 ±4.91 VS 4.20±3.27, 19.67 ± 2.94 VS 6.70±2.95, 11.25 ± 3.28 VS 5.70 ± 2.00 all p<0.01),but there was no difference between two groups in the aortic pressure in all corresponding subgroups(all P>0.05). (5) The left ventricular interior diameter(mm) in all subgroups of the DCM group was wider than those of the corresponding subgroups of the control group (4.25 ± 0.60 VS 3.08 ± 0.92 P<0.05 , 4.67 ± 0.61 VS 3.70 ± 0.59 p<0.01, 4.37 ± 0.64 VS 3.45 ± 0.37 p<0.01),and the thicknes of left ventricular free wall(mm) in the eight-week and twelve-week subgroups of the DCM group became thinner significantly than those of the corresponding subgroups of the control group (2.58 ± 0.38 VS 4.00 ± 0.58 p<0.01,3.13 ± 0.23 VS 3.55 ± 0.50 P<0.05), but there was no difference in two corresponding fourth-week subgroups (P>0.05) . (6)Compared with the corresponding subgroups of the control group, the ratio of left ventricle weight and body weight(mg/g) was increased significantly in the twelve-week subgroup.( 2.98 ± 0.15 VS 2.76 ± 0.10 F<0.05) ,but no differene of the ratio of left ventriculal weight and heart weight (mg/mg)was found in all subgroups of two groups (all P>0.05) .(7) Cardiac myocyte hypertrophy accompanied with nucleus augmentation,differentiation and defferiation . There were spot lysis, granular degeneration and vacuolation in themyocytic plasm. The intercellular space became enlargment. Those were observed in the rat myocardium in all sample; in the DCM group, but not occurried in the control group.更多还原