维格列汀通过调控炎症细胞因子和Nrf2途径促进糖尿病足溃疡创面愈合  

Vildagliptin promotes wound healing of diabetic foot ulcer by regulating inflammatory cytokines and Nrf2 pathway

作　　者：王晓娟[1] 曹海泉 袁宁 何明海 WANG Xiaojuan;CAO Haiquan;YUAN Ning;HE Minghai(Department of Endocrinology,Second Clinical College of North Sichuan Medical College,Nanchong Central Hospital,Nanchong 637000,China;Department of Critical Care Medicine,Nanchong Central Hospital;Department of Endocrinology,Nanchong Central Hospital)

机构地区：[1]川北医学院第二临床医学院,南充市中心医院内分泌科,南充637000 [2]南充市中心医院重症医学科 [3]南充市中心医院内分泌科

出　　处：《山西医科大学学报》2021年第1期76-81,共6页Journal of Shanxi Medical University

基　　金：南充市市校战略合作科技项目(18SXHZ0226)。

摘　　要：目的探究维格列汀对实验性糖尿病足溃疡创面的愈合作用及其机制。方法45只健康SD大鼠随机分为3组,即空白组、模型组和维格列汀组,每组15只。采用高糖高脂饲料+链脲佐菌诱发大鼠糖尿病足溃疡模型,造模成功后24 h,空白组和模型组予以等量生理盐水(2 ml/100 g)灌胃,维格列汀组按57 mg/kg剂量灌胃,分别于给药3,6,9 d,每组各取5只大鼠处死,取创面组织。采用HE染色观察创面组织病理变化。生化分析血糖、TC、TG、HDL和LDL浓度。ELISA检测创面组织TNF-α、IL-6和IL-1β水平。Western blot检测创面组织Nrf2、Keap1、collagen-Ⅰ、TGF-β和α-SMA蛋白表达。结果与空白组相比,模型组大鼠创面组织明显坏死脱落,给药6,9 d模型组TC、HDL、LDL、IL-1β、IL-6、TNF-α水平明显升高(均P<0.05),创面组织Nrf2、collagen-Ⅰ、TGF-β和α-SMA蛋白表达明显降低(均P<0.05)。给药9 d,与模型组比较,维格列汀组HDL、LDL、IL-1β、IL-6、TNF-α水平明显降低(均P<0.05),Nrf2、collagen-Ⅰ、TGF-β和α-SMA蛋白表达明显升高(均P<0.05)。结论维格列汀对糖尿病足溃疡创面延迟愈合具有潜在作用,可抑制炎症标志物、影响Nrf2途径,促进创面愈合。Objective To explore the effect of vildagliptin on wound healing in experimental model diabetic foot ulcer rats and its mechanism.Methods Forty-five healthy SD rats were randomly divided into 3 groups:control group,model group and vildagliptin group,with 15 rats in each group.The rat model of diabetic foot ulcer was induced by high-sugar and high-fat diet and streptozotocin.At 24 h after the establishment of the model,the rats were given double distilled water(10 mg/kg)in control group and model group,and 57 mg/kg vildagliptin in vildagliptin group.The wound healing rate was calculated after administration for 3,6,9 d.Five rats in each group were sacrificed to take the wound tissues.The pathological changes of wound tissue were observed by HE staining,the concentrations of blood glucose,TC,TG,HDL and LDL were analyzed by biochemical analysis,the levels of TNF-α,IL-6 and IL-1βin wound tissues were detected by ELISA,and the protein expression levels of Nrf2,Keap1,collagen-Ⅰ,TGF-βandα-SMA were detected by Western blot.Results Compared with control group,the wound tissue was obviously necrotic and exfoliated in model group,the levels of TC,HDL,LDL,IL-1β,IL-6 and TNF-αwere significantly increased after the administration for 6,9 d(all P<0.05),while the protein expression levels of Nrf2,collagen-Ⅰ,TGF-βandα-SMA were significantly decreased(all P<0.05).Compared with model group,the levels of HDL,LDL,IL-1β,IL-6 and TNF-αwere significantly decreased and the protein expression levels of Nrf2,collagen-Ⅰ,TGF-βandα-SMA were significantly increased in vildagliptin group after the administration for 9 d(all P<0.05).Conclusion Vildagliptin has a potential effect on the delay of wound healing of diabetic foot ulcer,and it can promote the wound healing by inhibiting the expression of inflammatory markers and affecting Nrf2 pathway.

关 键 词：糖尿病足溃疡 创面修复 维格列汀 

分 类 号：R587.2[医药卫生—内分泌]