AIM: To observe the effects of soluble transforming growth factor - β type Ⅱ receptor ( sTGFβR Ⅱ ) on cardiac functions after myocardial infarction ( MI ) in rats.METHODS: MI was induced in Sprague - Dawley ( SD ) rats by ligating the left anterior descending coronary artery.The rats surviving to the third day after MI were included in the study and randomly divided into MI group, pAd - sTGFβR Ⅱ group ( transfected with recombinant adenovirus vector expressing the extracellular domain gene of TGF - βR Ⅱ ), vector group and sham group.Four weeks later, the heart rate ( HR ), left ventricular end - diastolic dimension ( LVEDD ), left ventricular end - systolic dimension ( LVESD ) and ejection fraction ( EF ) were evaluated by echocardiograms.The expression of sTGFβR Ⅱ in myocardial tissues was observed under fluorescence microscope by frozen sectioning, and the expression of type Ⅰ and Ⅲ collagens was observed by Sirius red - saturated picric acid staining.The expression of matrix metalloproteinase 9 ( MMP - 9 ) at mRNA and protein levels was determined by RT - PCR and immunohistochemical method.The activity of MMP - 9 was assayed by gelatin zymography.RESULTS: Compared with sham group, HR, LVEDD, LVESD, type Ⅰ and Ⅲ collagen, mRNA and protein of MMP - 9, and the activity of MMP - 9 increased significantly ( P ＜ 0.01 ), and EF decreased ( P ＜ 0.01 ) in MI group and vector group.Compared with MI group, EF was increased ( P ＜ 0.01 ), but HR, LVEDD, LVESD, type Ⅰ and Ⅲ collagen, mRNA and protein expression of MMP -9 and the activity of MMP -9 decreased significantly ( P ＜0.01 ) in pAd -sTGFβR Ⅱ group, and all the parameters above were still higher than those in sham group.CONCLUSION: sTGFβR Ⅱ intervention improves the cardiac functions after MI by inhibiting TGF - β - mediated MMP - 9 expression.%目的:观察可溶性转化生长因子βⅡ型受体(sTGFβRⅡ)对大鼠心肌梗死(MI)后心功能的影响,并探讨其可能机制.方法:结扎左冠状动脉前降支,建立SD大鼠MI模型,3 d后存活大鼠进行实验,随机分为MI组、pAd-sTGFβRⅡ组(携带TGFβRⅡ胞外区基因即sTGFβRⅡ的重组腺病毒载体转染)和空载体组,并另设假手术组.4周后,超声心动图检测各组大鼠心率(HR)、左心室舒张末期直径(LVEDD)、左心室收缩末期直径(LVESD)和射血分数(EF)的变化,取心肌冰冻切片在荧光显微镜下观察sTGFβRⅡ基因在心肌组织中的表达,天狼星红-饱和苦味酸染色法检测Ⅰ、Ⅲ型胶原的表达,RT-PCR和免疫组化法分别检测基质金属蛋白酶9(MMP-9)mRNA和蛋白的表达,明胶酶谱法分析MMP-9的活性.结果:(1)与假手术组比较,MI组和空载体组HR、LVEDD、LVESD、Ⅰ和Ⅲ型胶原、MMP-9 mRNA和蛋白表达量及其活性均明显增加(P<0.01),EF明显下降(P<0.01).(2)与MI组比较,pAd-sTGFβRⅡ组HR、LVEDD和LVESD明显减小(P<0.01),EF明显升高(P<0.01);Ⅰ和Ⅲ型胶原、MMP-9 mRNA和蛋白表达量及其活性均明显下降(P<0.01),但仍高于假手术组.结论:sTGFβRⅡ干预能够改善MI后心功能,抑制TGF-β介导的MMP-9表达可能是其机制之一.
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