Department of Thoracic and Cardiovascular Surgery, Ewha Womans University, Seoul, Korea.
J Korean Med Sci. 2012 Jun;27(6):605-13. doi: 10.3346/jkms.2012.27.6.605. Epub 2012 May 26.
Pulmonary artery hypertension (PAH) causes right ventricular failure and possibly even death by a progressive increase in pulmonary vascular resistance. Bone marrow-derived mesenchymal stem cell therapy has provided an alternative treatment for ailments of various organs by promoting cell regeneration at the site of pathology. The purpose of this study was to investigate changes of pulmonary haemodynamics, pathology and expressions of various genes, including ET (endothelin)-1, ET receptor A (ERA), endothelial nitric oxide synthase (NOS) 3, matrix metalloproteinase (MMP) 2, tissue inhibitor of matrix metalloproteinase (TIMP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α in monocrotaline (MCT)-induced PAH rat models after bone marrow cell (BMC) transfusion. The rats were grouped as the control (C) group, monocrotaline (M) group, and BMC transfusion (B) group. M and B groups received subcutaneous (sc) injection of MCT (60 mg/kg). BMCs were transfused by intravenous injection at the tail 1 week after MCT injection in B group. Results showed that the average RV pressure significantly decreased in the B group compared with the M group. RV weight and the ratio of RH/LH+septum significantly decreased in the B group compared to the M group. Gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-α significantly decreased in week 4 in the B group compared with the M group. In conclusion, BMC transfusion appears to improve survival rate, RVH, and mean RV pressure, and decreases gene expressions of ET-1, ERA, NOS 3, MMP 2, TIMP, IL-6, and TNF-α.
肺动脉高压(PAH)通过肺血管阻力的逐渐增加导致右心室衰竭,甚至可能导致死亡。骨髓间充质干细胞治疗通过促进病变部位的细胞再生,为各种器官的疾病提供了一种替代治疗方法。本研究旨在探讨骨髓细胞(BMC)输注后肺动脉高压(PAH)大鼠模型的肺血液动力学、病理学和各种基因表达的变化,包括内皮素-1(ET-1)、内皮素受体 A(ERA)、内皮型一氧化氮合酶(NOS)3、基质金属蛋白酶(MMP)2、基质金属蛋白酶抑制剂(TIMP)、白细胞介素(IL)-6 和肿瘤坏死因子(TNF)-α。大鼠分为对照组(C)组、野百合碱(M)组和 BMC 输注(B)组。M 和 B 组均接受皮下(sc)注射野百合碱(MCT)(60mg/kg)。B 组在 MCT 注射后 1 周经尾静脉注射 BMC。结果表明,与 M 组相比,B 组平均 RV 压显著降低。与 M 组相比,B 组 RV 重量和 RH/LH+隔室比值显著降低。与 M 组相比,B 组在第 4 周时 ET-1、ERA、NOS 3、MMP 2、TIMP、IL-6 和 TNF-α的基因表达显著降低。总之,BMC 输注似乎可以提高生存率、RVH 和平均 RV 压,并降低 ET-1、ERA、NOS 3、MMP 2、TIMP、IL-6 和 TNF-α的基因表达。