骨髓间充质干细胞对大鼠梗死心肌胶原重构的双重调节作用

Dural modulation effects of mesenchymal stem cells implantation on myocardial collagen remodeling in a rat model of myocardial infarction

目的探讨骨髓间充质干细胞（MSC）对梗死心肌胶原重构的调节作用。方法采用结扎冠状动脉前降支的方法复制大鼠心肌梗死（MI）模型，随机分为假手术组（仅穿线不结扎冠状动脉，n=8）、MI＋PBS组（结扎冠状动脉＋心肌注射PBS溶液，n=8）和MI＋MSC组（结扎冠状动脉＋心肌注射MSC，n=8）。通过心脏超声检查、血液动力学检查和组织学染色方法分别检测左心室射血分数（LVEF）、短轴缩短率（Fs）、左心室收缩末压力（LVSP）、左心室舒张末压力（LVEDP）、左心室压最大升降速率（±dp／dtmax）、心肌梗死面积和梗死扩张指数等指标，评价MSC对大鼠心功能及心室重构的影响。同时采用免疫组化、RT—PCR、Westernblot等方法，测量胶原蛋白表达情况。结果（1）MI大鼠心室重构和心脏功能指标的检测结果：MI＋MSC组大鼠心肌梗死面积显著小于MI＋PBS组[（38．27±2．70）％比（46．20±3．17）％，t=5．386，P〈0．001]，Fs显著高于MI＋PBS组[（29．98±4．50）％比（23．43±3．34）％，t=-3．305，P：0．005]，LVSP显著高于MI＋PBS组[（113．63±10．81）mmHg（1mmHg：0．133kPa）比（99．254-16．76）mmHg，P〈0．05]，LVEDP显著低于MI＋PBS组[（12．10±4．28）mmHg比（20．08±4．26）mmHg，P〈0．05]，＋dp／dtmax显著高于MI＋PBS组[（4616．63±363．34）mmHg／s比（3912．75±248．79）lTlml-Ig／s，P〈0．05]，-dp／dtmax显著高于MI＋PBS组[（4254．63±324．34）mmHg／s比（3530．88±309．71）mmHg／s，P〈0．05]。（2）I型和Ⅲ型胶原蛋白表达水平的检测结果：MI＋MSC组大鼠梗死区I型和Ⅲ型胶原蛋白表达均显著高于MI＋PBS组，而非梗死区I型和Ⅲ型胶原蛋白表达均显著低于MI＋PBS组（P均〈0．05）。结论MSC通过促进MI大鼠梗死区胶原蛋白修复性合成，减少非梗死区胶原蛋白沉积，从而抑制心室重构，改善心脏功能。

Objective To investigate the modulation effects of mesenchymal stem cells （MSCs） implantation on the collagen remodeling in myocardial infarction. Methods Acute myocardial infarction （AMI） was induced in SD rats by left anterior descending coronary artery ligation, and the animals were assigned randomly into the Sham group, MI ＋ PBS group and MI ＋ MSCs group. Echocardiography and hemodynamic examinations were performed to evaluate the cardiac function. HE staining and Masson trichrome staining were used to evaluate the myocardial infarction size. Infarcted area and infarcted expansion index were calculated. The expression of collagens in infarcted hearts was evaluated by immunohistochemistry, RT-PCR and Western blot. Results （1） Infarct area was significantly reduced post MSCs transplantation [ MI ＋ MSCs vs. MI ＋ PBS： （38. 27 ± 2.70） % vs. （46.20 ± 3.17） %, P 〈 0. 001 ]. （2） Cardiac function was significantly improved post MSCs transplantation [ MI ＋ MSCs vs. MI ＋PBS： FS （%） ： 29. 98 ± 4. 50 vs. 23.43±3.34, P = 0. 005 ; LVSP （ mm Hg, 1 mm Hg = 0. 133 kPa） ： 113.63± 10.81vs. 99. 25±16.76, P〈0.05; LVEDP（mm Hg）- 12.10 ±4.28 vs. 20. 08 ±4.26, P〈0.05; ＋ dp/dtmax（mm Hg/s） ： 4616. 63 ±363.34 vs. 3912. 75 ±248. 79, P〈0. 05; - dp/dtmax （ram Hg/s） ： 4254. 63±324. 34 vs. 3530. 88 ±309. 71, P 〈0. 05]. （3） Collagen synthesis was enhanced in infarcted area and decreased in non-infarcted area post MSCs transplantation （ P 〈 0. 05 ）. Conclusions MSCs transplantation could enhance the collagen synthesis in infarcted area while decrease the deposition of collagen in non-infarcted area in this MI model. This may be one of the mechanisms by which ventricular remodeling is attenuated post MSCs transplantation.