摘要
目的探讨负压创面治疗(NPWT)糖尿病大鼠创面微血管的改变,进一步分析其潜在的分子机制。方法将96只大鼠随机分为NPWT组、NPWT+Tie-2组、纱布组(Gauze组)、Gauze+Tie-2组。NPWT组、NPWT+Tie-2组创面选择合适尺寸的VSD敷料覆盖,Gauze组和Gauze+Tie-2组进行常规纱布换药。NPWT+Tie-2组及Gauze+Tie-2组大鼠腹腔注射Tie-2抑制剂50 mg/kg。于术后1、3、7、10 d取创面肉芽组织行HE染色、免疫组化、mRNA及蛋白水平检测。结果NPWT组中Ang-1的mRNA及蛋白表达水平在术后第1、3天显著低于其他3组(P <0.05),术后第7、10天时呈增加趋势且其表达水平显著高于其他3组(P <0.05)。NPWT组中Ang-2的mRNA表达水平在术后第1、3天显著高于其他3组(P <0.05),术后第7、10天时急剧下降且其表达水平显著低于其他3组(P <0.05)。结论糖尿病创面愈合早期负压使Ang-2能够优先被Tie-2受体绑定并产生磷酸化作用,血管处于可塑和失稳定状态,促进微血管发芽;在创面愈合后期负压能够促使Ang-1和Tie-2受体优先绑定使激酶磷酸化过程提前出现,血管处于不可塑和稳定状态,创面微环境逐渐稳定并促进微血管成熟。因此,负压通过Ang/Tie-2信号通路促进糖尿病创面微血管成熟。
Objective To investigate the effect of negative pressure wound therapy （NPWT） on microvessel maturation, and further explore the potential molecular mechanism and relevant signal pathway. Methods Ninety-six diabetes mellitus rats were randomly divided into NPWT, NPWT＋Tie-2, Gauze and Gauze＋Tie-2 groups. NPWT and NPWT＋Tie-2 groups included 48 diabetes meilitus rats whose wounds were covered with Duoderm foam, followed by therapy using a vacuum-assisted closure device. Gauze and Gauze＋Tie-2 groups included 48 diabetes mellitus rats and were treated with petrolatum gauze. In addition, 48 diabetes mellitus rats in Gauze and Gauze ＋Tie-2 groups were injected intraperitoneally with Tie-2 kinase inhibitor （50 mg/kg）. Simultaneously immunohistocbemistry and reverse transcription-polymerase chain reaction and western blot were applied to detect protein expression of Ang-1, Ang-2, α-SMA and phosphorylation levels of tyrosine kinase receptor-2 （pTie-2）. Results Negative pressure wound therapy could promote the mRNA and protein expression levels of Ang-2, decrease the expression ratios of Ang-1/Ang-2, decrease the expression levels of Ang-1 and pTie-2 at early stage （l- 3 days） of wound healing. At later stage （7-10 days） of wound healing, negative pressure wound therapy could promote the protein expression levels of Ang-1, a-SMA and pTie-2, and decrease the mRNA and protein expression levels of Ang-2. Conclusion In the early stages of wound healing, NPWT could preferentially induce the occurrence of wound microvessel destabilized microenvironment, thereby increase initial angiogenesis in diabetic rats wound; and in later stages of wound healing, the NPWT could preferentially induce the occurrence of wound microvessel stabilized microenvironment, thereby promote microvascular reconstruction and maturation. Meanwhile Tie-2 inhibitors can mildly affect angiogenesis in the early stages of wound healing, but it can significantly influence microvascular reconstruction and maturation process in the late stages of wound healing, and the wound reconstruction and maturation process are mainly regulated by Ang/Tie-2 signaling pathways in diabetic rats wound.
作者
马战军
王天堂
毛丰刚
MA Zhan-jun;WANG Tian-tang;MAO Feng-gang(Department of Orthopedics,Aksu Prefecture First People＇s Hospital,Akstt,Xingjiang 843000,China)
出处
《中国骨与关节损伤杂志》
2018年第9期940-944,共5页
Chinese Journal of Bone and Joint Injury
基金
新疆维吾尔自治区科技人才培养项目(QN2016JC0593)
关键词
糖尿病创面
负压创面治疗
血管成熟
信号通路
血管生成素
酪氨酸激酶受体-2
Diabetic wound
Negative pressure wound therapy
Vessel maturation
Signaling pathway
Angiogenesis
Phosphorylation of tyrosine kinase receptor-2
作者简介
通讯作者：马战军．E-mail：mazhanjun@whu．edu．cn
