Schorr N, Sauerbier M, Germann G, Gebhard M M, Ofer N
Berufsgenossenschaftliche Unfallklinik Ludwigshafen, Klinik für Hand-, Plastische und Rekonstruktive Chirurgie - Schwerbrandverletztenzentrum, Ludwigshafen am Rhein.
Handchir Mikrochir Plast Chir. 2011 Dec;43(6):325-31. doi: 10.1055/s-0030-1267966. Epub 2011 Mar 3.
In spite of great advances in the field of composite tissue allotransplantations (CTA), there is still a major need for optimisation in terms of immunosuppression. Heat shock proteins are produced as a reaction of the body during a stress situation. Once elevated, they protect against a second stress and reduce ischaemia-reperfusion injury within transplantations. In the literature the effect of heat shock and HSP70 on rejection after CTA has not been described. The purpose of this experimental study was to examine the effect of heat shock proteins on rejection in a rat model of CTA. Evaluated was the effect of preconditioning by prior heat stress.
Brown Norway rats were systemically heated to a core temperature of 42 °C in order to up-regulate HSP70. The expression of HSP70 in muscle was measured by Western blot analysis and showed a peak 24 h after heat shock. Allogeneic hindlimb transplantations were performed between Brown Norway rats (donor) and Lewis rats (recipients). Group 1 (n=12) was preheated 24 h prior to transplantation. In group 2 (n=12) the transplantation was performed without prior heat shock. Group 3 (n=6) was used as a control group with syngeneic hindlimb transplantations between Lewis rats. Postoperatively the appearance of the transplanted hindlimb was evaluated every 12 h. The beginning of rejection was defined when plantar erythema and foot oedema could be observed at the same time. To verify these discrete signs of rejection, the observation was continued for a further 24 h. In this time erythema and oedema spread over the whole transplanted hindlimb. The rat was sacrificed after specimens of skin and muscle had been taken for histological assessment.
The rejection in group 1 (with preconditioning heat shock) began after 4.83±0.44 days, in group 2 (without heat shock) already after 3.88±0.53 days. The difference between these groups was significant because of the small standard deviation (Whitney-Mann U test: p<0.01).
In our model of allogeneic composite tissue transplantation, a heat shock and subsequent up-regulation of HSP70 led to a significant delay of the immunological rejection. As the graft rejection is an important item influencing the outcome of allogeneic transplantations, these results represent an option to improve the final functional outcome of composite tissue allotransplantations.
尽管复合组织同种异体移植（CTA）领域取得了巨大进展，但在免疫抑制方面仍有很大的优化需求。热休克蛋白是身体在应激状态下产生的反应产物。一旦升高，它们可预防二次应激，并减少移植过程中的缺血再灌注损伤。在文献中，尚未描述热休克和HSP70对CTA后排斥反应的影响。本实验研究的目的是在CTA大鼠模型中研究热休克蛋白对排斥反应的影响。评估了预先热应激预处理的效果。
将棕色挪威大鼠全身加热至核心温度42°C，以上调HSP70。通过蛋白质免疫印迹分析测量肌肉中HSP70的表达，结果显示热休克后24小时达到峰值。在棕色挪威大鼠（供体）和刘易斯大鼠（受体）之间进行同种异体后肢移植。第1组（n = 12）在移植前24小时进行预热。第2组（n = 12）在没有预先热休克的情况下进行移植。第3组（n = 6）用作对照组，进行刘易斯大鼠之间的同基因后肢移植。术后每12小时评估移植后肢的外观。当同时观察到足底红斑和足部水肿时，定义为排斥反应开始。为了验证这些排斥反应的离散迹象，观察持续另外24小时。在此期间，红斑和水肿蔓延至整个移植后肢。在取皮肤和肌肉标本进行组织学评估后，将大鼠处死。
第1组（有预处理热休克）的排斥反应在4.83±0.44天后开始，第2组（无热休克）在3.88±0.53天后开始。由于标准差小，这些组之间的差异具有统计学意义（惠特尼-曼恩U检验：p<0.01）。
在我们的同种异体复合组织移植模型中，热休克和随后HSP70的上调导致免疫排斥反应显著延迟。由于移植排斥是影响同种异体移植结果的一个重要因素，这些结果代表了一种改善复合组织同种异体移植最终功能结果的选择。
