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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/dt_(min))降低[(-4756.24±270.00)mm Hg/s(1 mm Hg=0.133 kPa)与(-2789.53±624.13)mm Hg/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 To investigate the effects of bone marrow stem cells on ventricular remodeling in heart failure after acute myocardial infarction (AMI) by regulating MMP2 / MMP1 / TIMP1 system. Methods Left anterior descending coronary artery of female SD rats was ligated to make acute myocardial infarction model. After 4 weeks, they were randomly divided into 2 groups: 7 rats in transplantation group were transplanted with bone marrow stem cells (5 × 10 ~ 6) derived from male SD rats to the scar area after infarction. Seven rats in control group were transplanted with equal volume of PBS to scar myocardium. Left ventricular morphology was assessed by HE staining and Masson staining. Immunohistochemical analysis of myocardial MMP2 and TIMP1 and scar area Ⅰ, Ⅲ collagen expression. Western blot analysis of MMP2 and TIMP1 protein changes. Results Some bone marrow stem cells showed fibroblast-like growth 21 days after transplantation. Inflammatory cells accumulate in the scarring area early after transplantation, and the number of inflammatory cells decreases 7 days after transplantation. Compared with the control group, the left ventricular ejection fraction and the shortening rate of left ventricular shortening in the transplantation group were significantly higher than those in the control group [(63.43 ± 3.97)% vs (36.20 ± 3.99)%, (31.71 ± 1.98)% vs (18.00 ± 2.07) %, P <0.05], and the decrease of dp / dt min (-4756.24 ± 270.00) mm Hg / s (1 mm Hg = 0.133 kPa) and (-2789.53 ± 624.13) mm Hg (36.36 ± 2.66)% vs (64.37 ± 2.36)%, P <0.05]. The area of infarct area was reduced (36.19 ± 0.83)% and (42.12 ± 1.88) %, P <0.05]. The expression of type Ⅰcollagen and type Ⅲ collagen in the scar tissue in the transplantation group were decreased, while the level of MMP2 protein and TIMP1 in myocardium were decreased. Conclusion Bone marrow stem cell transplantation through the MMP2 / TIMP1 lead to the dynamic changes of the collagen network, thereby improving the left ventricular remodeling after acute ischemic heart failure.