Zhang Y T, Li P, Luo L, Li-Tsang Z H P
Center of Rehabilitation Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhonghua Shao Shang Za Zhi. 2018 Oct 20;34(10):690-695. doi: 10.3760/cma.j.issn.1009-2587.2018.10.008.
To analyze the correlation between integrin β, 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. Thirty-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 β, 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 β, FAK, and ERK1/2 in epidermis of scar, the post injury time and the expressions of integrin β, FAK, and ERK1/2 in dermis of scar, the expressions of integrin β, 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 β, FAK, and ERK1/2 in dermis and those in epidermis of scar, the scar thickness and the post injury time. (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 β, 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 (=0.39, <0.05). There was significantly positive correlation between the expression of integrin β in epidermis of scar and the post injury time (=0.33, <0.05). There were no significantly correlations between the expressions of FAK and ERK1/2 in epidermis of scar and the post injury time (=-0.03, -0.04, >0.05). There was significantly negative correlation between the expression of FAK in dermis of scar and the post injury time (=-0.34, <0.05). There were no significantly correlations between the expressions of integrin β and ERK1/2 in dermis of scar and the post injury time (=0.07, -0.23, >0.05). There were significantly positive correlation between the expressions of integrin β, FAK, and ERK1/2 in dermis and those in epidermis of scar (=0.70, 0.60, 0.64, <0.01). (4) The expressions of integrin β, 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. In 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 β, FAK, and ERK1/2 of HS to external mechanical stimuli increases gradually within 4 months post injury.
分析烧伤患者瘢痕重塑期肥厚性瘢痕(HS)中整合素β、黏着斑激酶(FAK)、细胞外信号调节激酶1/2(ERK1/2)与伤后时间的相关性。采用方便抽样法,选取2013年5月至2016年4月在成都市第二人民医院烧伤整形科及陆军军医大学第一附属医院(原第三军医大学)烧伤研究所收治的34例患者的34个HS标本,另从上述科室6例行瘢痕切除植皮手术患者的供皮区获取正常皮肤标本,进行横断面观察性研究。采用温哥华瘢痕量表(VSS)评估瘢痕的高度、血管分布、色素沉着及柔韧性;采用超声测厚仪评估瘢痕厚度;采用免疫组织化学方法观察瘢痕及正常皮肤真皮和表皮中整合素β、FAK、ERK1/2的表达。采用Pearson相关分析瘢痕厚度与伤后时间、瘢痕表皮中整合素β、FAK、ERK1/2表达与伤后时间、瘢痕真皮中整合素β、FAK、ERK1/2表达与伤后时间、瘢痕真皮与表皮中整合素β、FAK、ERK1/2表达之间的相关性;采用局部加权散点平滑曲线拟合线展示瘢痕真皮与表皮中整合素β、FAK、ERK1/2表达、瘢痕厚度与伤后时间的非线性回归关系。(1)患者瘢痕VSS总分(8.3±2.3)分,其中高度(2.2±0.7)分,血管分布(2.0±0.8)分,色素沉着(2.3±0.7)分,柔韧性(1.9±0.7)分;瘢痕厚度(2.8±1.1)mm。(2)瘢痕真皮和表皮中整合素β、FAK、ERK1/2的表达高于正常皮肤。(3)瘢痕厚度与伤后时间呈显著正相关(r=0.39,P<0.05);瘢痕表皮中整合素β表达与伤后时间呈显著正相关(r=0.33,P<0.05);瘢痕表皮中FAK、ERK1/2表达与伤后时间无显著相关性(r=-0.03、-0.04,P>0.05);瘢痕真皮中FAK表达与伤后时间呈显著负相关(r=-0.34,P<0.05);瘢痕真皮中整合素β、ERK1/2表达与伤后时间无显著相关性(r=0.07、-0.23,P>0.05);瘢痕真皮与表皮中整合素β、FAK、ERK1/2表达呈显著正相关(r=0.70、0.60、0.64,P<0.01)。(4)瘢痕真皮和表皮中整合素β、FAK、ERK1/2表达在伤后12个月呈下降趋势,23个月呈上升趋势,3~4个月左右达到高峰,此后瘢痕表皮中机械信号分子表达逐渐下降,而瘢痕真皮中机械信号分子表达在伤后半年内维持在较高水平;瘢痕厚度在伤后1个月后持续增加。烧伤患者瘢痕重塑期,HS厚度在瘢痕形成早期随伤后时间延长而持续增加,伤后4个月内HS中整合素β、FAK、ERK1/2对外界机械刺激的敏感性逐渐增加。