ZHANG Nan, LI Jia-hui, WANG Jian-an, ZHANG Hong-kun
Department of Endocrinology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou 310016, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2008 Dec;36(12):1115-9.
Diabetic cardiomyopathy (DCM), an important cause of heart failure, is characterized by microvascular pathologies and interstitial fibrosis. Bone marrow mesenchymal stem cells (MSCs) are pluripotent, which can differentiate into cardiomyocytes and vascular endothelial cells. They also secrete angiogenic and antiapoptotic factors. However, little information is available about the effect of MSCs transplantation on diabetic heart.
MSCs were isolated from bone marrow of isogenic adult rats and cultured ex vivo. Eight weeks post streptozotocin injection, saline or exogenous MSCs labelled with 4'6-Diamidino-2-Phenylindole (DAPI) were injected into the femoral vein of diabetic rats and examined 4 weeks later by echocardiography, histopathologic analysis, reverse transcription polymerase chain reaction analysis for matrix metalloproteinase (MMP)-2, MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1, zymography analysis for activities of MMP-2 and Western blot analysis for troponin T.
Left ventricular posterior wall thickness and myocardial arteriolar density as well as the TIMP-1 mRNA and MMP-2 activity were significantly decreased in DCM group (P < 0.01 versus control group respectively), these changes were significantly attenuated by MSCs transplantation (P < 0.05 versus DCM). MSCs transplantation also significantly reduced fibrosis and downregulated MMP-9 mRNA in diabetic myocardium.
Intravenous MSCs transplantation could attenuate LV remodeling in DCM rats.
糖尿病性心肌病（DCM）是心力衰竭的一个重要病因，其特征为微血管病变和间质纤维化。骨髓间充质干细胞（MSCs）具有多能性，可分化为心肌细胞和血管内皮细胞，还能分泌血管生成因子和抗凋亡因子。然而，关于MSCs移植对糖尿病心脏影响的信息却很少。
从同基因成年大鼠的骨髓中分离出MSCs并在体外进行培养。链脲佐菌素注射8周后，将生理盐水或用4'6-二脒基-2-苯基吲哚（DAPI）标记的外源性MSCs注入糖尿病大鼠的股静脉，4周后通过超声心动图、组织病理学分析、基质金属蛋白酶（MMP）-2、MMP-9和基质金属蛋白酶组织抑制剂（TIMP）-1的逆转录聚合酶链反应分析、MMP-2活性的酶谱分析以及肌钙蛋白T的蛋白质印迹分析进行检测。
DCM组左心室后壁厚度、心肌小动脉密度以及TIMP-1 mRNA和MMP-2活性均显著降低（分别与对照组相比，P < 0.01），MSCs移植可显著减轻这些变化（与DCM组相比，P < 0.05）。MSCs移植还可显著减少糖尿病心肌中的纤维化并下调MMP-9 mRNA。
静脉注射MSCs移植可减轻DCM大鼠的左心室重构。
