自体脂肪干细胞局部注射对糖尿病足创面愈合及细胞因子、Wnt/β-catenin通路的影响
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摘要
目的研究自体脂肪干细胞局部注射对糖尿病足创面愈合及细胞因子、Wnt/β-catenin通路的影响。方法前瞻性选择2016年2月至2017年12月期间湖南中医药大学第一附属医院收治的糖尿病足患者,随机分为接受自体脂肪干细胞局部注射联合湿润烧伤膏换药的观察组,接受湿润烧伤膏换药的对照组。观察治疗后2周、3周、4周时的创面愈合率以及治疗过程中的创面感染率、创面愈合时间,测定2周后创面中细胞因子的含量、Wnt/β-catenin通路分子的表达量。结果观察组患者治疗2周、3周、4周后的创面愈合率高于对照组,治疗过程中的感染率低于对照组、平均愈合时间短于对照组(P <0. 05);观察组患者治疗后创面中血管内皮生长因子(VEGF)、表皮生长因子(EGF)、转化生长因子-β1(TGF-β1)的含量以及Wnt1、β连环蛋白(β-catenin)的mRNA表达量均高于对照组,白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、血管细胞黏附分子-1(VCAM-1)、肿瘤坏死因子-α(TNF-α)的含量以及糖原合成激酶-3β(GSK-3β)的mRNA表达量均低于对照组(P <0. 05)。结论自体脂肪干细胞局部注射能够促进糖尿病足创面的修复并调节细胞因子分泌、Wnt/β-catenin通路激活。
Objective To study the influence of autologous adipose stem cell injection on wound healing,cytokine,Wnt/β-catenin pathway in diabetic foot. Methods Diabetic foot patients admitted to our hospital from February 2016 to December 2017 were randomly divided into the observation group receiving autologous adipose stem cell injection combined with Shirun Shaoshang cream dressing replacement,the control group receiving Shirun Shaoshang cream dressing replacement. The wound healing rate at 2 and 4 weeks after treatmen and infection rate and wound healing time during therapy were observed. 2 weeks after treatment,the levels of cytokines and the expression of Wnt/β-catenin pathway molecules were measured. Results The wound healing rate of the observation group was higher than that of the control group after 2 and 4 weeks of treatment,the infection rate was lower than that of the control group,and the average healing time was shorter than that of the control group( P < 0. 05). The content of vascular endothelial growth factor( VEGF),epidermal growth factor( EGF),transforming growth factor-β1( TGF-β1) and the mRNA expression of Wnt1,β-catenin of observation group were higher than those of the control group,whereas the content of interleukin-1β( IL-1β),interleukin-18( IL-18),vascular cell adhesion molecule-1( VCAM-1),tumor necrosis factor-α( TNF-α)and the mRNA expression of glycogen synthase kinase-3β( GSK-3β) were lower than those of the control group. Conclusion Local injection of autologous adipose-derived stem cells can promote the repair of diabetic foot wounds and regulate the secretion of cytokines,the activation of Wnt/beta-catenin pathway.
Objective To study the influence of autologous adipose stem cell injection on wound healing,cytokine,Wnt/β-catenin pathway in diabetic foot. Methods Diabetic foot patients admitted to our hospital from February 2016 to December 2017 were randomly divided into the observation group receiving autologous adipose stem cell injection combined with Shirun Shaoshang cream dressing replacement,the control group receiving Shirun Shaoshang cream dressing replacement. The wound healing rate at 2 and 4 weeks after treatmen and infection rate and wound healing time during therapy were observed. 2 weeks after treatment,the levels of cytokines and the expression of Wnt/β-catenin pathway molecules were measured. Results The wound healing rate of the observation group was higher than that of the control group after 2 and 4 weeks of treatment,the infection rate was lower than that of the control group,and the average healing time was shorter than that of the control group( P < 0. 05). The content of vascular endothelial growth factor( VEGF),epidermal growth factor( EGF),transforming growth factor-β1( TGF-β1) and the mRNA expression of Wnt1,β-catenin of observation group were higher than those of the control group,whereas the content of interleukin-1β( IL-1β),interleukin-18( IL-18),vascular cell adhesion molecule-1( VCAM-1),tumor necrosis factor-α( TNF-α)and the mRNA expression of glycogen synthase kinase-3β( GSK-3β) were lower than those of the control group. Conclusion Local injection of autologous adipose-derived stem cells can promote the repair of diabetic foot wounds and regulate the secretion of cytokines,the activation of Wnt/beta-catenin pathway.
引文
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[11] Xu J,Min D,Guo G,et al. Experimental study of epidermal growth factor and acidic fibroblast growth factor in the treatment of diabetic foot wounds[J]. Exp Ther Med,2018,15(6):5365-5370.
[12]郜敏,刘琰,章雄,等. NLRP3炎症复合体与糖尿病慢性难愈性创面关系的研究进展[J].中华损伤与修复杂志(电子版),2015,10(5):434-438.
[13] Vaseghi H,Pornour M,Djavid GE,et al. Association of the gene expression variation of tumor necrosis factor-αand expressions changes of dopamine receptor genes in progression of diabetic severe foot ulcers[J]. Iran J Basic Med Sci,2017,20(11):1213-1219.
[14] Qi W,Yang C,Dai Z,et al. High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling[J]. Diabetes,2015,64(4):1407-1419.
[15]赵亚男,刘明,张玥,等.糖尿病溃疡中Wnt/β-catenin信号通路表达的变化[J].中国病理生理杂志,2015,31(11):2033-2038.
[2] Al-Busaidi IS. Diabetic Foot Disease in Oman:A Call for More Research[J]. Oman Med J,2017,32(4):354-355.
[3]赵月强,朱占永,李爱林,等.自体脂肪干细胞在糖尿病足创面治疗中的应用[J].临床外科杂志,2018,26(1):63-66.
[4]白俊清,高占峰.糖尿病足的临床综合治疗[J].临床和实验医学杂志,2016,15(16):1654-1657.
[5] Gadelkarim M,Abushouk AI,Ghanem E,et al. Adipose-derived stem cells:Effectiveness and advances in delivery in diabetic wound healing[J]. Biomed Pharmacother,2018,14(107):625-633.
[6] Lopes L,Setia O,Aurshina A,et al. Stem cell therapy for diabetic foot ulcers:a review of preclinical and clinical research[J]. Stem Cell Res Ther,2018,9(1):188.
[7] Shi GJ,Shi GR,Zhou JY,et al. Involvement of growth factors in diabetes mellitus and its complications:A general review[J]. Biomed Pharmacother,2018,101:510-527.
[8] Sridharan K,Sivaramakrishnan G. Growth factors for diabetic foot ulcers:mixed treatment comparison analysis of randomized clinical trials[J]. Br J Clin Pharmacol,2018,84(3):434-444.
[9] Ojalvo AG,Acosta JB,MaríYM,et al. Healing enhancement of diabetic wounds by locally infiltrated epidermal growth factor is associated with systemic oxidative stress reduction[J]. Int Wound J,2017,14(1):214-225.
[10]武姗,刘洋,朱旅云,等.转化生长因子β及其受体在糖尿病足创面愈合过程中作用机制的研究进展[J].中国糖尿病杂志,2017,25(6):569-571.
[11] Xu J,Min D,Guo G,et al. Experimental study of epidermal growth factor and acidic fibroblast growth factor in the treatment of diabetic foot wounds[J]. Exp Ther Med,2018,15(6):5365-5370.
[12]郜敏,刘琰,章雄,等. NLRP3炎症复合体与糖尿病慢性难愈性创面关系的研究进展[J].中华损伤与修复杂志(电子版),2015,10(5):434-438.
[13] Vaseghi H,Pornour M,Djavid GE,et al. Association of the gene expression variation of tumor necrosis factor-αand expressions changes of dopamine receptor genes in progression of diabetic severe foot ulcers[J]. Iran J Basic Med Sci,2017,20(11):1213-1219.
[14] Qi W,Yang C,Dai Z,et al. High levels of pigment epithelium-derived factor in diabetes impair wound healing through suppression of Wnt signaling[J]. Diabetes,2015,64(4):1407-1419.
[15]赵亚男,刘明,张玥,等.糖尿病溃疡中Wnt/β-catenin信号通路表达的变化[J].中国病理生理杂志,2015,31(11):2033-2038.