Diabetes and dyslipidemia. A new model for transplant coronary artery disease.
Diabetes and dyslipidemia. A new model for transplant coronary artery disease.
复制标题
糖尿病和血脂异常。
DOI：
10.1161/01.cir.97.21.2160
复制
发表时间：
1998
期刊：
影响因子：
37.8
通讯作者：
Valantine,H
中科院分区：
文献类型：
--
作者：
Hoang,K;Chen,YD;Reaven,G;Zhang,L;Ross,H;Billingham,M;Valantine,H
临床观察表明，移植性冠状动脉疾病（TxCAD）是免疫介导的，但可能因代谢紊乱而加速。为了进一步研究糖尿病和血脂异常在TxCAD发生中的作用，我们建立了异位心脏移植大鼠模型。方法与结果：采用主要组织相容性复合物不匹配的近交系大鼠进行异位心脏移植（aci - lewis同种异体移植）。移植后注射链脲佐菌素（80 mg/kg）诱导糖尿病（DM）；饲喂60%高果糖饮食（+F）会使血脂异常恶化。同种异体移植分为4组：(1)+DM/+F；(2) + DM /−F;(3)−DM / + F;(4)−DM/−F。对照组为异位移植物（Lewis to Lewis, +DM/±F）。所有动物每天服用环孢素（5 mg/kg）。在组织学切片上评估存活bbb30天的移植物的TxCAD水平，并将内膜厚度分为0至5级。所有接受链脲佐菌素治疗的动物在2周内都患上了糖尿病，血浆葡萄糖浓度比非糖尿病患者增加了4倍。仅在糖尿病异体移植物中观察到严重的TxCAD。糖尿病异体移植的TxCAD平均等级为3.2±0.5，而糖尿病异体移植的TxCAD平均等级为1.1±0.4 (P<0.03)，非糖尿病异体移植的TxCAD平均等级为零（P≤0.0001）。与常规饮食相比，果糖喂养导致甘油三酯升高1.5倍，胆固醇升高1.3倍（−F），但对TxCAD的发展没有独立贡献。结论：这些发现提示糖尿病相关的代谢紊乱在异位ACI-to-Lewis大鼠心脏移植中TxCAD的发展中起重要作用。在主要组织相容性复合物错配、糖尿病和血脂异常大鼠的TxCAD模型中，可以进一步描述TxCAD的免疫和代谢机制，并评估其预防方法。
Background—Clinical observations suggest that transplant coronary artery disease (TxCAD) is immunologically mediated but may be accelerated by metabolic derangements. We developed a rat model of heterotopic heart transplantation in the presence of diabetes and dyslipidemia to further study their role in TxCAD development.Methods and Results—Major histocompatibility complex–mismatched strains of inbred rats underwent heterotopic heart transplantation (ACI-to-Lewis allografts). Diabetes (DM) was induced by streptozotocin injection (80 mg/kg) after transplantation; dyslipidemia was worsened by feeding of a 60% high-fructose diet (+F). Allograft transplants were divided into four groups: (1) +DM/+F; (2) +DM/−F; (3) −DM/+F; and (4) −DM/−F. Isograft transplants (Lewis to Lewis, +DM/±F) were controls. All animals received daily cyclosporine (5 mg/kg). Grafts surviving >30 days were evaluated for TxCAD on histological sections and graded 0 to 5 for intimal thickness. All streptozotocin-treated animals were diabetic within 2 weeks, with fourfold increases in plasma glucose concentrations versus nondiabetics. Severe TxCAD was observed in diabetic allografts only. The mean grade of TxCAD in diabetic allografts was 3.2±0.5 versus 1.1±0.4 in diabetic isografts (P<0.03) and zero TxCAD in nondiabetic allografts (P≤0.0001). Fructose feeding resulted in a 1.5-fold higher triglyceride and a 1.3-fold higher cholesterol level versus the regular diet (−F) but showed no independent contribution to the development of TxCAD.Conclusions—These findings suggest that metabolic derangements associated with diabetes play an important role in TxCAD development in heterotopic ACI-to-Lewis rat heart transplantation. In this model of TxCAD in major histocompatibility complex–mismatched, diabetic, and dyslipidemic rats, immunologic and metabolic mechanisms that contribute to TxCAD can be further delineated and approaches to its prevention assessed.