牛磺酸对扩张型心肌病大鼠左室基质金属蛋白酶1表达的影响

EFFECT OF MMP1 EXPRESSION OF LEFT VENTRICLE WITH TAURINE ON DILATED CARDIOMYOPATHY OF RAT

目的 :探讨牛磺酸对扩张型心肌病大鼠模型左室基质金属蛋白酶 1(m atrix m etalloproteinases,MMP1)表达的影响。方法 :随机选取 2周龄 Wistar大鼠 5 0只 ,雄性 ,体重 (6 2 .5 6± 5 .12 ) g,以呋喃唑酮诱导扩张型心肌病模型 ,随机分为模型组(DCM)、牛磺酸干预 组 ( Tau)、牛磺酸干预 组 ( Tau)、牛磺酸假干预组 (TC)及空白对照组 (NC) ,每组又根据不同时间点分为 4周和 12周二个亚组。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舒张末期内径 (L VEDD)、左室收缩末期内径 (L VESD)、左室射血分数 (EF)及左室缩短率 (FS)。应用 HE染色光镜下观察心肌组织的病理学改变。应用免疫组化方法检测左室心肌 型胶原含量的变化。应用 RT- PCR技术检测左室心肌 MMP1的表达活性。结果 :DCM模型组及 TC组4、12周亚组大鼠与 NC组相应亚组比较 ,L VEDD和 L VESD均明显增大 (P均 <0 .0 5 ) ;FS、EF均明显降低 (P均 <0 .0 1) ;心肌细胞肥大 ,胞浆灶性溶解 ,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 ,左室心肌 型胶原明显升高 (P均 <0 .0 1) ;左室心肌组织 MMP1m RNA基因表达水平均明显升高 (P均 <0 .0 1)。而 Tau组和 Tau组上述指标无明显变化

Objective:To elucidated the effect of MMP1 expression of left ventricle with taurine on dilated cardiomyopathy of rats.Methods:50 Wistar male rats,aged two weeks, body weight (62.56±5.12)g on average, were studied randomly. All rats were divided to DCM model group(DCM), taurine group Ⅰ(ⅠTau), taurine group Ⅱ(ⅡTau), taurine control group(TC) and normal control group (NC), sub-divided to three groups,4-week sub-group and 12-week sub group, according to the different time points, respectively. Echocardiography was used for the assessment of the left ventricular end diastolic diameter(LVEDD), left ventricular end systolic diameter(LVESD), fractional shortening(FS)and ejection fraction(EF). The myocardial pathological pattern was detected by HE staining. The contents of collagen Ⅲ in the heart were determined by immunohistochemincal staining. The expression pattern of MMP1 was detected by using RT-PCR method.Result:The LVEDD and LVESD in DCM group and TC group at 4 W, 12 W sub-group were increased more significantly (P<0.01) than NC group. The FS and EF in DCM group and TC group at 4 W, 12 W sub-group were decreased more significantly (P<0.01) than NC group.The HW/BW ratio in DCM group and TC group at 12 W sub-group was inceased significantly (P<0.05), whereas the LVM/HW ratio was no of significance (P>0.05) in all group. Compared with NC group, there was cardiac myocyte hypertrophy accompanied with nucleus augmentation, differentiation and defferiation in the DCM group and TC group at all sub-group. Also, there were spot lysis, granular degeneration and vacuolation in the myocytic plasm in some degree. The intercellular space became enlarged 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 and TC group whereas there was no significance inⅠTau group and ⅡTau group (P>0.05). The mRNA expression of MMP1 was increased significantly in DCM group TC group (P<0.01) whereas no significances inⅠTau group and ⅡTau group at their sub-group (P>0.05).Conclusion:The expression of MMP1 was time-dependently increased in the heart of DCM rat model induced by Furazolidone, which was involved in the left ventricular remodeling all the time. After Taurine was used, the activity of MMP1 was down regulated so that the left ventricular remodeling was turned over. Taurine could be a new hopeful method to treat DCM.