15-Deoxyspergualinの移植心冠動脈硬化様病変と血小板由来成長因子A mRNAの発現程度に対する影響
| Autor: | ZHANG, Xilong, HACHIDA, Mitsuhiro, LU, Hua, FURUKAWA, Hiroshi, HOSHI, Hironobu, KOYANAGI, Hitoshi |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Zdroj: | 東京女子医科大学雑誌. 68(3):66-72 |
| ISSN: | 0040-9022 |
| Popis: | 移植心の冠動脈硬化様病変は心移植遠隔期の重大な合併症である.今回我々は免疫抑制剤である15-deoxyspergualin(DSG)の移植後冠動脈硬化様病変と血小板由来成長因子A(PDGF-A)mRNAの発現程度における影響について検討した.ドナーにWistar-Kingラット,レシピエントにLewisラットを用いて,腹腔内異所性心移植を行った.DSG投与群(n=7)にはDSG 5mg/kg/dayを,対照群にはcyclosporin A 10mg/kg/dayを腹腔内投与した.両群とも移植後60日目に移植心を摘出し,血管径50μm以上のすべての冠動脈を観察し,Lurieの評価法により硬化様病変率とその程度を算出し評価した.また拒絶反応の程度は,PCRとNorthern blot analysis法で移植心PDGF-A発現に対する影響についても比較検討し,以下の結論を得た.1)DSG群では有意に冠動脈硬化様病変は抑制されていた.2)拒絶反応の程度はDSG投与群と対照群の差が認められなかった.3)DSG群投与の移植心ではPDGF-Aが低下していた.免疫抑制剤DSG投与群では冠動脈硬化様病変の抑制が認められた.この効果はDSGがPDGF-Aを抑制したことと関連している可能性があると考えられる. Graft coronary arteriosclerosis is a major impediment to the long-term success of heart transplantation. We evaluated the effects of 15-deoxyspergualin (DSG) on graft coronary arteriosclerosis and on platelet-derived growth factor-A (PDGF-A) mRNA expression of graft myocardium after heterotopic heart transplantation in a rat model, and compared the effects to those of cyclosporine treatment. Two groups of Lewis rats (n=7 each group) underwent heterotopic heart transplantation from Wistar-King donors and were treated with either DSG (5 mg/kg/day) or cyclosporine A (10 mg/kg/day), (control group). Histological evaluations of rejection and coronary arteriosclerosis, as well as Northern blot analysis of graft PDGF-A mRNA expression were made 60 days after transplantation. No significant difference in the degree of rejection was found between the two groups. However, the degree of coronary arterial intimal thickening in the DSG group was significantly less than that seen in the control group (p < 0.01). Moreover, the incidence of diseased vessels observed and the degree of platelet-derived growth factor-A mRNA expression of graft myocardium were significantly lower in the DSG group when compared with the control group (p < 0.05). These results suggest that DSG shows a greater efficacy than cyclosporine A in preventing graft coronary disease, and this efficacy was probably associated with the depressed expression of graft PDGF-A in the DSG group. |
| Databáze: | OpenAIRE |
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