烧伤后制动致创面愈合延迟的机制研究

The Mechanism of Wound Healing Delay by Immobilization After Extensive Burn

目的分析临床烧伤创面愈合与患者抑郁的相关性并构建大面积烧伤后制动的小鼠模型,证实烧伤后制动致创面愈合延迟的作用及相关机制。方法纳入106例烧伤患者,用汉密尔顿抑郁量表(HAMD)评估抑郁与烧伤面积及愈合率的关系;用24只BALB/c小鼠构建大面积烧伤模型,并分为制动组、活动组、活动+镇痛组和制动+镇痛组,评估体质量、创面愈合及抑郁等表型;ELISA检测患者及小鼠外周血炎性指标肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、IL-8、抗抑郁指标脑源性神经营养因子(brain derived neurotrophic factor,BDNF)及营养指标血清白蛋白(serum albumin,ALB)表达。结果抑郁与烧伤面积呈正相关、与创面愈合呈负相关(P均<0.01);抑郁患者TNF-α、IL-6、IL-8升高,BDNF降低(P均<0.01);制动组小鼠悬尾静止次数与时间较活动组增加,创面愈合延迟,血清TNF-α、IL-6、IL-8增高,BDNF降低(P均<0.01);制动+镇痛组较活动+镇痛组小鼠创面愈合缓慢,同样伴TNF-α、IL-6、IL-8增高和BDNF降低,联合烧伤创面局部镇痛小鼠创面愈合减慢(P均<0.01)。结论烧伤后制动的患者创面愈合能力降低与诱发抑郁和炎性相关因子增多有关,适度运动可改善抑郁并下调炎性因子水平,进而促进烧伤创面愈合。

Objective Analyzing the correlation between wound healing and depression in burn patients,and establishing mouse model of immobilization-induced depression after burn,we were intended to verify the role of immobilization on burn wound healing.Methods Firstly,a total of 106 burn patients were selected as the research objects.Hamilton scale(HAMD)was used to evaluate the relationship between depression and burn area or wound healing rate.Then,twenty four BALB/c mice were used to construct burn models and divided into immobilization group,activity group,immobilization plus local analgesia group,and activity plus local analgesia group to mainly evaluate the roles of immobilization in burn wound healing.Finally,the expressions of cytokines tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-8,brain derived neurotrophic factor(BDNF),and serum albumin(ALB)in peripheral blood of patients and mice were detected by ELISA.Results Depression degree of burn patients was positively correlated with burn area and negatively correlated with wound healing rate(P all<0.01).The expression of TNF-α,IL-6 and IL-8 were increased and BDNF was decreased in severely depressed patients(P all<0.01).After burn,the rest time span and frequency of tail suspension in the immobilization group was prolonged,and the wound healing speed was decreased(P all<0.01).Comparing with the activity group,the frequency and time span of tail suspension in the immobilization group were significantly increased,the wound healing was delayed,and the expression of serum TNF-α,IL-6 and IL-8 were increased,while BDNF was decreased.Comparing with the activity plus local analgesia group,the wound healing of mice in immobilization plus local analgesia group was slower,with the increased expression of TNF-α,IL-6,IL-8 and decreased BDNF,but the wound healing of mice combined with local analgesia on burn wounds was slower.Conclusion The decrease of wound healing ability in burn patients with depression is related to immobilization,with the increased inflammatory factors and decreased BDNF,and moderating exercise after burn can improve the expression level of inflammatory and depression-related factors and accelerate the burn wound healing.