对小剂量胰岛素局部注射促进脂肪干细胞移植成活及改善糖尿病创面愈合临床观察

Clinical observation of low dose insulin local injection for promotion of adipose derived stem cell transplantation survival and improvement of diabetic wound healing

目的探讨小剂量胰岛素局部注射促进脂肪干细胞(ADSCs)和移植皮瓣成活以及改善糖尿病慢性难愈性创面愈合的临床效果。方法选择2017年6月至2019年1月于新疆医科大学第七附属医院诊断为糖尿病慢性溃疡难愈性创面患者共110例,随机将其分为空白组、对照组、小剂量组(0.5 U正规胰岛素)、中剂量组(1.0 U正规胰岛素)和高剂量组(2.0 U正规胰岛素),每组22例;所有患者均采用游离皮瓣移植术和局部注射ADSCs,连续治疗4周。于治疗2周和4周观察创面愈合程度、皮瓣存活率、创面血流量,ELISA法检测愈合-未愈界面组织热休克蛋白-90(HSP-90)、血管内皮生长因子(VEGF)、转化生长因子-β(TGF-β)、白介素-1(IL-1)表达水平,CD31免疫组化检测微血管数量,葡萄糖氧化酶法检测血糖水平。结果小剂量组创面愈合程度、皮瓣存活率和创面血流量显著高于其他各组(P<0.05);小剂量组创面组织HSP-90、VEGF、TGF-β和IL-1表达水平显著高于其他各组(P<0.05);小剂量组微血管数量显著多于其他各组(P<0.05)。各组血糖水平比较差异无统计学意义(P>0.05)。结论小剂量胰岛素局部应用可明显促进糖尿病慢性难愈性创面移植ADSCs和游离皮瓣存活,改善创面愈合质量,可能与促进创面组织HSP-90、VEGF、TGF-β和IL-1表达以及微血管形成有关,同时对血糖影响较小,具有较好的安全性和有效性。

Objective To analyze the clinical effect of low dose insulin local injection for survival of adipose derived stem cells(ADSCs)and transplanted flap and diabetic chronic refractory wound healing.Methods A total of 110 diabetic patients with chronic ulcer difficult healing wounds from June 2017 to January 2019 were enrolled and divided randomly into blank group,control group,low dose group(0.5 U insulin),medium dose group(1.0 U insulin)and high dose group(2.0 U insulin),each group of 22 cases.The patients all got free skin flap transplantation and local injection of ADSCs for four weeks.Compared wound healing degree,survival rate of skin flaps and blood flow of wound,expressions of HSP-90,VEGF,TGF-βand IL-1 in healing-unhealed interface tissue detected by ELISA,microvessel number detected by CD31 immunohistochemistry and blood sugar level measured by glucose oxidase method among the groups after two and four weeks.Results The wound healing degree,survival rate of skin flaps and blood flow of wound after two and four weeks in low dose group were all significantly higher than the other groups,expressions of HSP-90,VEGF,TGF-βand IL-1 were higher,and microvessel number were more than the other groups(P<0.05).While there was no significant difference in blood sugar level among the groups(P>0.05).Conclusion It can greatly promote survival of ADSCs and transplanted flap,improve quality of wound healing in diabetic chronic refractory wound with low dose insulin local injection,which may be related to higher expressions of HSP-90,VEGF,TGF-β,IL-1 and microvessel number,without influence of blood sugar,and has better safety and efficacy.