骨髓干细胞移植通过基质金属蛋白酶及其抑制剂降低大鼠缺血性心力衰竭心室重构  

Bone marrow mesenchymal cell transplantation reduces left ventricular remodeling in heart failure following acute myocardial infarction

作　　者：郭豫涛[1] 李小鹰[1] 吴迪[2] 姚克群[2] 陈平[3] 马康涛[3] 周春燕[3] 

机构地区：[1]解放军总医院老年心血管病一科,北京100853 [2]空军总医院超声科 [3]北京大学医学部生物化学系

出　　处：《中华心血管病杂志》2006年第9期784-788,共5页Chinese Journal of Cardiology

基　　金：国家"973"科研经费资助项目(G2000056906)

摘　　要：目的探讨骨髓干细胞通过调节基质金属蛋白酶2／基质金属蛋白酶抑制剂1（MMP2／TIMP1）系统改善急性心肌梗死后心力衰竭心室重构。方法结扎雌性SD大鼠左冠状动脉制作急性心肌梗死模型。4周后随机分为2组：移植组大鼠7只，移植雄性SD大鼠来源的骨髓干细胞（5×10^6）到梗死后瘢痕区。对照组大鼠7只，移植等体积的PBS到瘢痕心肌。通过HE染色和Masson染色评价左室形态。免疫组织化学分析心肌MMP2和TIMP1和瘢痕区Ⅰ、Ⅲ型胶原表达情况。经Western杂交检测MMP2和TIMP1蛋白变化。结果部分骨髓干细胞在移植后21天呈纤维母细胞样生长。移植后早期有炎症细胞聚集在瘢痕区，移植后7天炎症细胞减少。与对照组相比，移植组大鼠左室射血分数和左室短轴缩短率提高[（63．43±3．97）％与（36．20±3．99）％，（31．71±1．98）％与（18．00±2．07）％，P〈0．05]，左室压力下降最大值（dp／dtmin）降低[（-4756．24±270．00）mmHg／s（1mmHg：0．133kPa）与（-2789．53±624．13）mmHg／s，P〈0．05]，左室厚度率增加[（76．34±2．66）％与（64．37±2．36）％，P〈0．05]，梗死区面积缩小[（36．19±0．83）％与（42．12±1．88）％，P〈0．05]。移植组大鼠瘢痕区Ⅰ型胶原表达升高，Ⅲ型胶原降低；心肌MMP2蛋白水平降低而TIMP1水平升高。结论骨髓干细胞移植通过MMP2／TIMP1导致胶原网络的动态变化，从而改善急性缺血后衰竭心脏的左室重构。Objective Bone marrow mesenchymal cell （MSC） transplantation has been shown to improve heart failure but the mechanism and the subsequent effects are unclear. We tested the hypothesis that MSC transplantation reduces left ventricular remodeling through the MMP/TIMP system in heart failure following acute myocardial infarction. Methods Female SD rats underwent coronary artery ligation to induce myocardial infarction. Four weeks later, the rats were divided into the test group （ n = 7 ） and the control group （n =7）, respectively. The donor MSCs were harvested and expanded from male SD rats （5 × 10^6 in 50 μl PBS） and injected into the ischemic myocardium, while the control group received the same volume of PBS. Left ventricular morphology was then evaluated in both groups through staining with H＆E and Masson＇s trichrome. Immunohistochemical staining was used to examine the expressions of MMP2 and TIMP1, as well as type Ⅰ and type Ⅲ collagens, in the scar zones. The protein levels of MMP2 and TIMP1 were determined by Western blotting. Results MSC differentiated into fibroblast-like cells at 21 days after transplantation in the test group. In addition, many inflammatory cells infiltrated and aggregated in the scar area, but this effect was reduced at day 7 after transplantation. The following changes were noted in the test group compared to the control group ： ejection fraction and shortening fraction were higher [ （63. 43 ＋- 3.97 ） % vs. （36. 20＋-3.99） %, （31.71 ＋-1.98） % vs. （18.00 ＋-2.07） %, P〈0.05]; dp/dtmin was reduced [ （ - 4756. 24 ＋- 270. 00） mm Hg/s vs. （ - 2789. 53 ＋- 624. 13 ） mm Hg/s, P 〈 0.05 ] ; the left ventricular thinning ratio was significantly higher[ （76. 34 ＋- 2. 66 ） % vs. （64. 37 ＋- 2. 36） %, P 〈 0. 05 ] ; the infarct size was smaller [ （36. 19 ＋- 0. 83 ） % vs. （42. 12 ＋- 1.88 ） %, P 〈 0. 05 ] ; type Ⅰ collagen expression in the scar area was much higher; type Ⅲ collagen expression was much lower

关 键 词：基质金属蛋白酶 蛋白酶抑制药 心力衰竭 充血性 心肌梗塞 

分 类 号：R541.6[医药卫生—心血管疾病]