烧伤患者瘢痕重塑期增生性瘢痕机械信号转导分子与伤后时间的相关性研究

Research on the correlation between mechanical signaling molecules of hypertrophic scar and post injury time in burn patients in scar remodeling stage

目的分析烧伤患者增生性瘢痕重塑期整合素β1、局部黏着斑激酶（FAK）及胞外信号调节激酶1/2（ERK1/2）表达与伤后时间的相关性。方法采用方便抽样法纳入2013年5月—2016年4月成都市第二人民医院烧伤整形科、陆军军医大学（原第三军医大学）第一附属医院全军烧伤研究所的34例住院烧伤患者34个增生性瘢痕，另取上述单位6例瘢痕切除植皮手术患者的供皮区正常皮肤，进行横断面、观察性研究。采用温哥华瘢痕量表评估瘢痕高度、血管化、色素沉着、柔软度情况，超声诊断仪测量瘢痕厚度，免疫组织化学法观察瘢痕和正常皮肤真皮和表皮的整合素β1、FAK、ERK1/2表达。对伤后时间与瘢痕厚度，伤后时间分别与瘢痕表皮整合素β1、FAK、ERK1/2表达量，伤后时间分别与瘢痕真皮整合素β1、FAK、ERK1/2表达量，瘢痕真皮整合素β1、FAK、ERK1/2分别与表皮相同蛋白酶表达量行Pearson相关分析。采用局部多项式回归拟合分析瘢痕表皮和真皮中整合素β1、FAK、ERK1/2以及瘢痕厚度与伤后时间的非线性回归关系。结果（1）本组患者的瘢痕评分总分为（8.3±2.3）分，其中高度（2.2±0.7）分、血管化（2.0±0.8）分、色素沉着（2.3±0.7）分、柔软度（1.9±0.7）分；瘢痕厚度为（2.8±1.1）mm。（2）瘢痕表皮和真皮中整合素β1、FAK、ERK1/2表达量均多于正常皮肤。（3）伤后时间与瘢痕厚度呈明显正相关（r＝0.39，P〈0.05）。伤后时间与瘢痕表皮整合素β1表达量呈明显正相关（r＝0.33，P〈0.05），与瘢痕表皮FAK、ERK1/2表达量无明显相关性（r＝－0.03、－0.04，P〉0.05）。伤后时间与瘢痕真皮FAK表达量呈明显负相关（r＝－0.34，P〈0.05），与瘢痕真皮整合素β1、ERK1/2表达量无明显相关性（r＝0.07、－0.23，P〉0.05）。瘢痕表皮和真皮的整合素β1、FAK、ERK1/2表达量呈明显正相关（r＝0.70、0.60、0.64，P〈0.01）。（4）瘢痕表皮和真皮中整合素β1、FAK、ERK 1/2的表达量从伤后1～2个月的下降趋势转变为伤后2～3个月期间的上升趋势，且在伤后3～4个月期间达到顶峰，此后表皮中机械信号转导分子表达量逐渐下降，而真皮中机械信号转导分子表达量在伤后半年内维持在较高的水平。瘢痕厚度从伤后1个月后呈现稳定上升趋势。结论烧伤患者瘢痕重塑期，增生性瘢痕厚度在瘢痕形成早期随伤后时间持续增加；增生性瘢痕中整合素β1、FAK、ERK1/2对外界机械力的易感性在受伤后4个月内逐渐增强。

ObjectiveTo analyze the correlation between integrin β1, focal adhesion kinase （FAK）, extracellular signal-regulated kinase 1/2 （ERK1/2） of hypertrophic scar （HS） and post injury time in burn patients in scar remodeling stage.MethodsThirty-four patients with 34 HS specimens admitted to Department of Burns and Plastic Surgery of Chengdu No.2 Hospital and Institute of Burn Research of the First Affiliated Hospital of Army Medical University （originally the Third Military Medical University） from May 2013 to April 2016 were recruited by convenient sampling method, and normal skin specimens were obtained from donor sites of another 6 patients from the above-mentioned departments who had scar resection and skin grafting for this cross-sectional and observational study. Vancouver Scar Scale （VSS） was used to assess the height, vascularity, pigmentation, and pliability of scars. Diasonograph was used to assess scar thickness. Immunohistochemical method was used to observe the expressions of integrin β1, FAK, and ERK1/2 in dermis and epidermis of scar and normal skin. Correlations between the post injury time and the scar thickness, the post injury time and the expressions of integrin β1, FAK, and ERK1/2 in epidermis of scar, the post injury time and the expressions of integrin β1, FAK, and ERK1/2 in dermis of scar, the expressions of integrin β1, FAK, and ERK1/2 in dermis and those in epidermis of scar were analyzed by Pearson correlation analysis. Locally estimated scatterplot smoothing curve fitting line was used to demonstrate the non-linear regression relationship between the expressions of integrin β1, FAK, and ERK1/2 in dermis and those in epidermis of scar, the scar thickness and the post injury time.Results（1） The total VSS score of scars of patients was （8.3±2.3） points, with height scored （2.2±0.7） points, vascularity scored （2.0±0.8） points, pigmentation scored （2.3±0.7） points, and pliability scored （1.9±0.7） points. The thickness of scar was （2.8±1.1） mm. （2） The expressions of integrin β1, FAK, and ERK1/2 in dermis and epidermis of scar were more than those in normal skin. （3） There was significantly positive correlation between the scar thickness and the post injury time （r=0.39, P〈0.05）. There was significantly positive correlation between the expression of integrin β1 in epidermis of scar and the post injury time （r=0.33, P〈0.05）. There were no significantly correlations between the expressions of FAK and ERK1/2 in epidermis of scar and the post injury time （r=-0.03, -0.04, P〉0.05）. There was significantly negative correlation between the expression of FAK in dermis of scar and the post injury time （r=-0.34, P〈0.05）. There were no significantly correlations between the expressions of integrin β1 and ERK1/2 in dermis of scar and the post injury time （r=0.07, -0.23, P〉0.05）. There were significantly positive correlation between the expressions of integrin β1, FAK, and ERK1/2 in dermis and those in epidermis of scar （r=0.70, 0.60, 0.64, P〈0.01）. （4） The expressions of integrin β1, FAK, and ERK1/2 in dermis and epidermis of scar were changed from downtrend in 1 to 2 months post injury to uptrend in 2 to 3 months post injury, which reached the peak around 3 to 4 months post injury. Hereafter the expressions of mechanical signaling molecules in epidermis of scar were gradually declined, while the expressions of mechanical signaling molecules in dermis of scar were at a quite high level within half a year post injury. Scar thickness was steadily increased after 1 month post injury.ConclusionsIn scar remodeling stage of burn patients, the HS thickness increases continuously along with the increasing post injury time in the early stage of scar formation. The vulnerability of integrin β1, FAK, and ERK1/2 of HS to external mechanical stimuli increases gradually within 4 months post injury.