热休克蛋白70在大鼠原位及异位移植心脏中的表达

Mehta N K, Carroll M, Sykes D E, Tan Z, Bergsland J, Canty J, Bhayana J N, Hoover E L, Salerno T A

Division of Cardiothoracic Surgery, State University of New York at Buffalo 14214, USA.

J Surg Res. 1997 Jul 1;70(2):151-5. doi: 10.1006/jsre.1997.5123.

Heat shock proteins (hsp) are intracellular proteins that are rapidly synthesized in response to a variety of stress factors. Recent studies in rats have shown that these proteins can elicit a lymphocyte response during cardiac allograft rejection. We studied the expression of the inducible (i) and constitutive (c) forms of hsp70 in rat cardiac allograft and isograft recipients to evaluate their utility as indicators of transplant rejection. Heterotopic transplantation of rat hearts was performed, using Lewis to Lewis isografts and ACI to Lewis allografts. Sham-operated rats were used as controls. Transplanted isograft, allograft, and native hearts of the transplant recipients and their livers and spleens were harvested at 5 days posttransplant and analyzed for hsp70 (i) and (c) expression by Western blots. Seven animals were studied in each group. Isografts at 3 and 60 days and allografts at 8 days were also studied. Quantification of band densities was carried out by laser densitometry. Physiological function of the native hearts of the transplant recipients was studied using Langendorff preparations. High levels of hsp70 (i) were noted in the transplanted and native hearts of the transplant recipients but not in their livers or spleens or in the hearts of the sham-operated control animals. Myocardial function of the native hearts of the transplant recipients was not significantly different from that of the controls. Significantly higher levels of hsp70 (c) were present in mild and severely rejecting allografts compared with controls and nonrejecting isografts. In the rat model of heterotopic cardiac transplantation, high levels of hsp70 (i) in the native hearts of the allograft and isograft recipients suggest a transplant-related, cardiac-specific stress process, not previously described. Heat shock protein 70 (c) expression is significantly increased during early and late allograft rejection and may serve as an indicator of transplant rejection.

热休克蛋白（hsp）是细胞内蛋白质，可响应多种应激因素而快速合成。最近在大鼠身上的研究表明，这些蛋白质在心脏同种异体移植排斥反应期间可引发淋巴细胞反应。我们研究了大鼠心脏同种异体移植和同基因移植受体中hsp70的诱导型（i）和组成型（c）形式的表达，以评估它们作为移植排斥指标的效用。采用Lewis到Lewis同基因移植以及ACI到Lewis同种异体移植进行大鼠心脏异位移植。假手术大鼠用作对照。在移植后5天收获移植受体的移植同基因移植物、同种异体移植物和天然心脏及其肝脏和脾脏，并通过蛋白质印迹分析hsp70（i）和（c）的表达。每组研究7只动物。还研究了3天和60天的同基因移植物以及8天的同种异体移植物。通过激光密度测定法对条带密度进行定量。使用Langendorff标本研究移植受体天然心脏的生理功能。在移植受体的移植心脏和天然心脏中发现高水平的hsp70（i），但在其肝脏或脾脏以及假手术对照动物的心脏中未发现。移植受体天然心脏的心肌功能与对照无显著差异。与对照和未发生排斥的同基因移植物相比，轻度和重度排斥的同种异体移植物中hsp70（c）水平明显更高。在大鼠异位心脏移植模型中，同种异体移植和同基因移植受体天然心脏中高水平的hsp70（i）提示存在一种与移植相关的、心脏特异性应激过程，此前未被描述。热休克蛋白70（c）在同种异体移植早期和晚期排斥反应期间表达显著增加，可能作为移植排斥的一个指标。