基质金属蛋白酶1在扩张型心肌病大鼠中的表达特性

Expression of matrix metalloproteinase on dilated cardiomyopathy rat

目的探讨基质金属蛋白酶1(matrixmetalloproteinase,MMP1)在扩张型心肌病(DCM)大鼠中的表达特性。方法2周龄Wistar大鼠60只,雄性,体重(61.19±6.99)g,随机分为DCM组和空白对照(NC)组,每组又根据不同时间点分为4、8、12周3个亚组,利用呋喃唑酮诱导建立DCM模型。应用多功能超声心动图诊断仪检测不同时间点大鼠模型左室内径、左室射血分数(LVEF)及左室缩短率(LVFS)。苏木精伊红染色观察心肌组织的病理学改变。应用免疫组化方法检测Ⅲ型胶原含量的变化。应用RTPCR技术检测左室心肌MMP1的表达活性。结果DCM组4周、12周亚组大鼠的左室内径较NC组相应亚组明显增大(均P<0.01);DCM组3个亚组的LVFS及LVEF均较NC组相应亚组明显降低(4周,12周,均P<0.01,8周,P<0.05);DCM组12周亚组心脏重量/体重比值增加(P<0.05)。与NC组比较,DCM组各亚组大鼠心肌细胞肥大,胞质灶性溶解,呈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,间质胶原纤维明显增生;心肌间质Ⅲ型胶原相对值明显增加(均P<0.01);心肌MMP1mRNA基因表达水平明显上升(4周,8周,均P<0.01,12周,P<0.05),但随着病程的发展有下调趋势。结论利用呋喃唑酮诱导建立大鼠DCM模型,为DCM的临床和实验研究提供理想的动物模型。

Objective:To detect the expression pattern of matrix metalloproteinase (MMP1 ) on dilated cardiomyopathy rat. Method: Sixty Wistar male rats, aged two weeks, body weight (~61.19 ±~6.99 )g in average, were studied randomly. All rats were divided into dilated cardiomyopathy model (DCM) group and normal control (NC) group, sub-divided into three group, 4-week sub-group, 8-week sub-group and 12-week sub- group, respectively. Echocardiography was used for the assessment of the left ventricular(LV) chamber dimensions, fractional shortening(FS)and ejection fraction(EF). The contents of collagen Ⅲ in the heart were determined by enzymoimmunohistochemincal staining. The myocardial pathological patterns were detected by HE staining. The expression patterns of MMP1 were detected using RT-PCR method. Result:The LV chamber dimensions in DCM group at 4W, 12W sub-group were increased significantly (P<~0.01 ) than that in NC group. The FS and EF in DCM group were decreased significantly (4 W, P<~0.01 , 8 W, P<~0.05 , respectively) than that in NC group. The HW/BW ratio in DCM group at 12 W sub-group was increased significantly (P<~0.05 ) than in NC group. Compared with NC group, there were much more significant cardiac myocyte hypertrophy accompanied with nucleus augmentation, differentiation and defferiation in the DCM group at all sub-group. Also, there were spot lysis, granular degeneration and vacuolation in the myocytic plasm at some degree. The intercellular space became larger where the myocardium interstitial collagen fibers were increased significantly. The comparative contents of the myocardium interstitial collagen Ⅲ were increased significantly (P<~0.01 ) in DCM group at all sub-group. The mRNA expression of MMP1 was increased significantly in DCM group (4 W, 8 W, P<~0.01 , 12 W, P<~0.05 , respectively), whereas down regulated during the developing time.Conclusion: The left ventricle dilates and LVM increases on DCM Wistar rat model induced by Furazolidone, which provides a powerful model for clinical and basic research on DCM. MMP1 involves in the left ventricular remodeling in this rat model.