Boyle Andrew J, Schuster Michael, Witkowski Piotr, Xiang Guosheng, Seki Tetsunori, Way Kerrie, Itescu Silviu
University of Melbourne, Department of Medicine, St Vincent's Hospital, Fitzroy, Victoria, 3065, Australia.
J Renin Angiotensin Aldosterone Syst. 2005 Mar;6(1):33-7. doi: 10.3317/jraas.2005.004.
Animal studies have demonstrated the efficacy of endothelial progenitor cells (EPCs) in preventing left ventricular (LV) remodelling following myocardial infarction (MI). Preliminary human studies are underway, yet no studies have demonstrated efficacy in combination with standard medical therapy, i.e. angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Nude rats underwent left anterior descending coronary artery ligation to induce MI. Animals were randomised to receive no treatment (MI, n = 5), quinapril 200 mg/L + metoprolol 2 g/L (ACE/BB, n = 5), two million EPCs intravenously (EPC, n = 5)or both (ACE/BB + EPC [n = 5]), then sacrificed after two weeks treatment. ACE/BB resulted in a 75% reduction in fibrosis in the region remote from the MI (p < 0.05), but EPC therapy had little effect here. Conversely, EPC therapy induced neovascularisation at the peri-infarct rim, thereby preventing peri-infarct apoptosis by 81% (p < 0.05). Acting via different but complementary mechanisms, the combination of ACE/BB + EPCs resulted in a greater overall improvement in LV function on echocardiography than either therapy alone. Clinical trials using stem cell therapy in conjunction with standard medical treatment are warranted.
动物研究已证明内皮祖细胞（EPCs）在预防心肌梗死（MI）后左心室（LV）重构方面的疗效。初步的人体研究正在进行中，但尚无研究证明其与标准药物治疗（即血管紧张素转换酶（ACE）抑制剂和β受体阻滞剂）联合使用时的疗效。将裸鼠的左冠状动脉前降支结扎以诱导心肌梗死。将动物随机分为不接受治疗组（MI，n = 5）、喹那普利200 mg/L + 美托洛尔2 g/L组（ACE/BB，n = 5）、静脉注射200万个EPCs组（EPC，n = 5）或两者联合组（ACE/BB + EPC [n = 5]），治疗两周后处死。ACE/BB使心肌梗死远端区域的纤维化减少了75%（p < 0.05），但EPC治疗在此处几乎没有效果。相反，EPC治疗在梗死周边诱导了新血管形成，从而使梗死周边的细胞凋亡减少了81%（p < 0.05）。通过不同但互补的机制起作用，ACE/BB + EPCs联合治疗在超声心动图上使左心室功能的总体改善比单独使用任何一种治疗方法都更大。有必要开展将干细胞治疗与标准药物治疗相结合的临床试验。
