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高同型半胱氨酸血症可导致同基因和异基因大鼠心脏移植中移植血管硬化加速。

Hyperhomocyst(e)inemia induces accelerated transplant vascular sclerosis in syngeneic and allogeneic rat cardiac transplants.

作者信息

Cook Judith W, Yin Qiang, Malinow M Rene, Orloff Susan L

机构信息

Department of Surgery, Oregon Health and Science University, Portland 97201, USA.

出版信息

Am J Transplant. 2002 Mar;2(3):244-51. doi: 10.1034/j.1600-6143.2002.20309.x.

Abstract

Chronic rejection (CR) and transplant vascular sclerosis (TVS) cause the majority of graft failures in cardiac transplantation. Hyperhomocyst(e)inemia [hH(e)] is associated with human TVS without a proven causal relationship. This study investigated the effect of hH(e) on graft survival and TVS in allogeneic and syngeneic rat cardiac transplants. Lewis recipients of heterotopic F344 heart allografts, received normal or hH(e)-inducing (folate, methionine) diets [controls: syngeneic transplanted [+/- hH(e), + CsA] and nontransplanted rats [+/- hH(e), +/- CsA]]. Serial plasma homocyst(e)ine [H(e)] levels were measured. TVS was assessed in clinically rejected grafts and a subset of pre-rejection normal diet allografts (day 64) (neointimal index, NI). The hH(e) diet elevated plasma H(e) levels. When compared with normal diet controls (n = 9), hH(e) diet allografts (n = 9) had decreased time to onset of CR (40 +/- 9 vs. 72 +/- 10d, p = 0.02), and graft failure (64 +/- 10 vs. 107 +/- 12d, p = 0.009). hH(e) diet allografts at rejection (n = 9, 64d) had more severe TVS (NI = 68 +/- 2) than both time-matched normal diet allografts (NI = 49 +/- 6, n = 8, 64d, p <0.001) and normal diet allografts at rejection (NI = 58 +/- 5, n = 9, 107d, p = 0.007). hH(e) induced TVS in syngeneic grafts (NI=50 +/- 3, n = 10 vs. NI = 5 +/- 3, n = 10, 130d, p <0.001). hH(e) accelerated rejection and increased the severity of TVS in allogeneic cardiac transplants, and induced TVS in syngeneic cardiac transplants.

摘要

慢性排斥反应(CR)和移植血管硬化(TVS)是导致心脏移植中大多数移植物失败的原因。高同型半胱氨酸血症[hH(e)]与人类TVS相关,但尚未证实存在因果关系。本研究调查了hH(e)对同种异体和同基因大鼠心脏移植中移植物存活和TVS的影响。异位F344心脏同种异体移植的Lewis受体接受正常或诱导hH(e)的(叶酸、蛋氨酸)饮食[对照组:同基因移植[±hH(e),+环孢素A(CsA)]和未移植大鼠[±hH(e),±CsA]]。测量系列血浆同型半胱氨酸[H(e)]水平。在临床排斥的移植物和一部分排斥前正常饮食的同种异体移植物(第64天)中评估TVS(内膜增生指数,NI)。hH(e)饮食可提高血浆H(e)水平。与正常饮食对照组(n = 9)相比,hH(e)饮食的同种异体移植物(n = 9)发生CR的时间缩短(40±9天对72±10天,p = 0.02),移植物失败时间缩短(64±10天对107±12天,p = 0.009)。排斥时hH(e)饮食的同种异体移植物(n = 9,64天)的TVS比时间匹配的正常饮食同种异体移植物(NI = 49±6,n = 8,64天,p<0.001)和排斥时正常饮食的同种异体移植物(NI = 58±5,n = 9,107天,p = 0.007)更严重。hH(e)在同基因移植物中诱导TVS(NI = 50±3,n = 10对NI = 5±3,n = 10,130天,p<0.001)。hH(e)加速了同种异体心脏移植的排斥反应并增加了TVS的严重程度,且在同基因心脏移植中诱导了TVS。

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