NGF、IGF1在烧伤后增生性瘢痕组织中的表达及意义

The expression and clinical significance of NGF and IGF1 in hypertrophic scar tissue after burn

目的探讨神经生长因子(NGF)及胰岛素样生长因子1(IGF1)在烧伤后增生性瘢痕组织中的表达情况及临床意义。方法选取增生性瘢痕患者114例为研究对象,所有患者均行手术治疗,术中取患者增生性瘢痕组织作为瘢痕组,并留取患者自身正常组织作为对照组;随访6个月,根据患者是否复发分为复发组(36例)和未复发组(78例)。采用荧光定量PCR(qRT-PCR)法检测组织中NGF、IGF1 mRNA及相关炎性因子水平,放射免疫法检测组织中NGF、IGF1蛋白水平;采用温哥华瘢痕量表(VSS)评价瘢痕严重程度,跨皮水分丢失(TEWL)评估增生性瘢痕的表皮屏障功能,并分析NGF、IGF1水平与相关炎性因子、VSS量表评分、TEWL净丧失量、瘢痕形成时间的相关性。结果瘢痕组NGF、IGF1 mRNA及蛋白水平均高于对照组(P<0.05),炎性因子单核细胞趋化蛋白-1(MCP-1)、白细胞介素(IL)-1β、IL-6及IL-8 mRNA水平高于对照组(P<0.05);复发组中NGF、IGF1蛋白水平均高于未复发组(P<0.05);患者增生性瘢痕组织VSS量表评分为(11.47±2.35)分,瘢痕形成时间为(57.32±18.64)d,增生性瘢痕组织TEWL值明显高于正常皮肤组织(t=20.544,P=0.000),TEWL净丧失量为(7.42±2.03)g/(m^(2)·h)。Pearson结果显示,瘢痕组织NGF、IGF1 mRNA水平分别与MCP-1、IL-1β、IL-6及IL-8 mRNA呈正相关(P<0.05),瘢痕组织中NGF蛋白水平与VSS量表评分、TEWL净丧失量、瘢痕形成时间均呈正相关(P<0.05),瘢痕组织中IGF1蛋白水平与VSS量表评分、TEWL净丧失量、瘢痕形成时间均呈正相关(P<0.05),此外,瘢痕组织中NGF蛋白水平与IGF1蛋白水平也呈正相关(P<0.05)。结论增生性瘢痕组织中NGF、IGF1 mRNA及蛋白水平均升高,且两者与炎性因子、瘢痕状态、表皮屏障功能及瘢痕形成时间有关,有望成为临床干预瘢痕的新的治疗靶点。

Objective To investigate the expression and clinical significance of nerve growth factor(NGF)and insulin-like growth factor 1(IGF1)in hypertrophic scar tissue after burn.Methods A total of 114 hypertrophic scar patients from March 2017 to May 2021 were selected.All patients received surgical treatment.The hypertrophic scar tissue of the patients was taken as the scar group during the operation,and the patient′s own normal tissues were retained as a control group.The patients were followed up for 6 months and divided into recurrence group(36 cases)and non-recurrence group(78 cases).Fluorescence quantitative PCR(qRT-PCR)method was used to detect the levels of NGF,IGF1 and related inflammatory factors mRNAs in the tissue,and radioimmunoassay was used to detect the levels of NGF and IGF1 proteins in the tissue.The Vancouver Scar Scale(VSS)was used to evaluate the severity of scars.The transepidermal water loss(TEWL)was used to evaluate the epidermal barrier function of hypertrophic scars.The correlation between the levels of NGF and IGF1 and the levels of related inflammatory factors,the VSS scale score,the net loss of TEWL and the scar formation time were analyzed.Results The levels of NGF and IGF1 mRNAs and proteins in the scar group were significantly higher than those in the control group(P<0.05);so were the levels of monocyte chemoattractant protein-1(MCP-1),interleukin-1β(IL-1β),IL-6 and IL-8 mRNA(P<0.05).The levels of NGF and IGF1 proteins in recurrent group were significantly higher than those in non-recurrent group(P<0.05).The VSS score of hypertrophic scar tissue was 11.47±2.35,and the scar formation time was 57.32±18.64 days.The TEWL value of hypertrophic scar tissue was significantly higher than that of normal skin tissue(t=20.544,P=0.000),and the net loss of TEWL was 7.42±2.03 g/m^(2)·h.Pearson results showed that the levels of NGF and IGF1 mRNA in scar tissue were positively correlated with MCP-1,IL-1β,IL-6 and IL-8 mRNA(P<0.05);the level of NGF protein in scar tissue was positively correlated with the VSS score,the net loss of TEWL and the scar formation time(P<0.05);the level of IGF1 protein in scar tissue was positively correlated with the VSS score,the net loss of TEWL and the scar formation time(P<0.05).In addition,the level of NGF protein in scar tissue was also positively correlated with the level of IGF1 protein(P<0.05).Conclusion The levels of NGF and IGF1 mRNA and protein in hypertrophic scar tissue are increased,and both of them are related to inflammatory factors,scar state,epidermal barrier function and scar formation time.They are expected to become new therapeutic targets for clinical intervention of scars.