Hachida M, Zhang X, Lu H, Hoshi H, Koyanagi H
Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical College, Japan.
Jpn Circ J. 1999 Apr;63(4):303-8. doi: 10.1253/jcj.63.303.
Graft coronary arteriosclerosis (GCA) that results in proliferative and obstructive lesions limits the long-term success of cardiac transplantation. Despite extensive study, the pathogenic mechanisms underlying GCA are still unclear and therapeutic strategies for this condition have been inadequate. In this study, we compared the therapeutic effectiveness of cyclosporine A (CsA), 15-deoxyspergualin (DSG), and Multiglycosidorum tripterygii (MT) on GCA. In addition, we studied the correlation between the extent of GCA and the degree of platelet-derived growth facter (PDGF)-A chain mRNA expression in cardiac grafts. Lewis rats receiving heterotropic heart transplants from Wistar King donors were treated with 10 mg kg(-1) day(-1) of CsA (n=7), 5 mg kg(-1) day(-1) of DSG (n=7) or 30 mg kg(-1) day(-1) of MT (n=7) respectively. Histological evaluation of coronary arteriosclerosis and Northern blot analysis of cardiac allograft PDGF-A chain mRNA expression were conducted on day 60 after transplantation. Varying levels of GCA were observed in the 21 transplanted hearts. Significant differences in both the degree of PDGF-A mRNA expression and the extent of GCA were found among the 3 groups. GCA was significantly reduced in allografts treated with MT or DSG in comparison with the level seen in CsA-treated grafts. A significant correlation was found between PDGF-A chain mRNA expression and the grade of arterial intimal thickening (r=0.76, p<0.05) as well as with the incidence of diseased vessels (r=0.82, p<0.01). Our results indicate that both MT and DSG are more effective in the treatment of GCA than CsA. In our cardiac allografts, the degree of PDGF-A chain mRNA expression correlated well with the extent of GCA, suggesting that PDGF-A may play an important role in the development of transplant-related GCA.
导致增殖性和阻塞性病变的移植冠状动脉粥样硬化（GCA）限制了心脏移植的长期成功率。尽管进行了广泛研究，但GCA的致病机制仍不清楚，针对这种情况的治疗策略也不充分。在本研究中，我们比较了环孢素A（CsA）、15-去氧精胍菌素（DSG）和雷公藤多苷（MT）对GCA的治疗效果。此外，我们研究了GCA程度与心脏移植物中血小板衍生生长因子（PDGF）-A链mRNA表达程度之间的相关性。分别用10 mg·kg⁻¹·d⁻¹的CsA（n = 7）、5 mg·kg⁻¹·d⁻¹的DSG（n = 7）或30 mg·kg⁻¹·d⁻¹的MT（n = 7）治疗接受来自Wistar King供体的异位心脏移植的Lewis大鼠。在移植后第60天对冠状动脉粥样硬化进行组织学评估，并对心脏同种异体移植物PDGF-A链mRNA表达进行Northern印迹分析。在21个移植心脏中观察到不同程度的GCA。3组之间在PDGF-A mRNA表达程度和GCA程度上均存在显著差异。与CsA治疗的移植物相比，MT或DSG治疗的同种异体移植物中GCA显著降低。发现PDGF-A链mRNA表达与动脉内膜增厚程度（r = 0.76，p < 0.05）以及病变血管发生率（r = 0.82，p < 0.01）之间存在显著相关性。我们的结果表明，MT和DSG在治疗GCA方面比CsA更有效。在我们的心脏同种异体移植物中，PDGF-A链mRNA表达程度与GCA程度密切相关，表明PDGF-A可能在移植相关GCA的发展中起重要作用。
