Wang B H, Ye C, Stagg C A, Lin M, Fawcett T, VanderKolk C A, Udelsman R
Division of Plastic and Reconstructive Surgery at The Johns Hopkins University School of Medicine, Baltimore, Md, USA.
Plast Reconstr Surg. 1998 Mar;101(3):776-84. doi: 10.1097/00006534-199803000-00029.
The cellular response to a wide variety of stresses results in the synthesis of a family of stress response proteins termed heat shock proteins. Recent studies have demonstrated that heat shock proteins produced in response to an initial stress seem to protect against subsequent unrelated stresses. Importantly, hyperthermia-induced heat shock proteins provided protection from ischemia/reperfusion injury in several organ transplantation models. We hypothesized that free musculocutaneous flap survival could be improved by enhancing the flap's tolerance to relative ischemia by the prior induction of heat shock proteins. Accordingly, we determined the heat shock protein response in skin and muscle after systemic or local heating and examined the effect on free musculocutaneous flap survival in a rat model. Free musculocutaneous flaps incorporating thigh adductor muscles and a 2 x 6-cm2 skin paddle were transplanted to the ipsilateral groin in three groups of male Wistar rats. Systemically heated rats (n = 6) were anesthetized and incubated for 30 minutes at 42 degrees C 6 hours before free musculocutaneous tissue transfer. Locally heated rats (n = 6) were anesthetized, and their donor site anterior thigh was placed for 30 minutes on a heating block set at 44 degrees C 6 hours before free tissue transfer. Control rats (n = 5) did not have heating pretreatment but underwent identical anesthesia. Animals were sacrificed on postoperative day 3, at which time skin loss (cm2) and muscle viability, quantified by nitroblue tetrazolium staining time, were assessed in a blinded fashion. The skin and muscle from the free flap were analyzed for HSP72 mRNA and protein using quantitative Northern and Western blot techniques. All free musculocutaneous flaps were viable. However, the locally and systemically heated rats demonstrated a marked improvement of skin survival, which correlated with increased skin levels of HSP72. There were no differences in nitroblue tetrazolium muscle staining times or muscle levels of HSP72 among the three groups. These findings suggest that prior heat-induced heat shock proteins result in improvement in musculocutaneous flap survival, which may have direct clinical applications, especially in high-risk patients.
细胞对多种应激的反应会导致一类被称为热休克蛋白的应激反应蛋白的合成。最近的研究表明，因初始应激而产生的热休克蛋白似乎能保护细胞免受随后不相关应激的影响。重要的是，在几种器官移植模型中，热诱导产生的热休克蛋白能提供对缺血/再灌注损伤的保护。我们推测，通过预先诱导热休克蛋白来增强皮瓣对相对缺血的耐受性，可以提高游离肌皮瓣的存活率。因此，我们测定了全身或局部加热后皮肤和肌肉中的热休克蛋白反应，并在大鼠模型中研究了其对游离肌皮瓣存活的影响。将包含股内收肌和2×6平方厘米皮肤瓣的游离肌皮瓣移植到三组雄性Wistar大鼠的同侧腹股沟。全身加热组大鼠（n = 6）在游离肌皮组织移植前6小时麻醉，并在42℃下孵育30分钟。局部加热组大鼠（n = 6）麻醉后，在游离组织移植前6小时将其供体部位大腿前部置于设置为44℃的加热块上30分钟。对照组大鼠（n = 5）未进行加热预处理，但接受相同的麻醉。术后第3天处死动物，此时以盲法评估皮肤损失面积（平方厘米）和通过硝基蓝四唑染色时间量化的肌肉活力。使用定量Northern印迹和Western印迹技术分析游离皮瓣的皮肤和肌肉中的HSP72 mRNA和蛋白。所有游离肌皮瓣均存活。然而，局部和全身加热组大鼠的皮肤存活率有显著提高，这与皮肤中HSP72水平的升高相关。三组之间硝基蓝四唑肌肉染色时间或肌肉中HSP72水平没有差异。这些发现表明，预先热诱导产生的热休克蛋白可提高肌皮瓣的存活率，这可能具有直接的临床应用价值，尤其是在高危患者中。
