银杏叶提取物注射液对糖尿病足溃疡模型大鼠创面恢复的作用及机制研究  

Effect of Ginkgo biloba injection on the recovery of diabetic foot ulcer model rats’wounds and its mechanism

作　　者：何丰来 肖聪[1] 龙能吉 刘利娟 He Fenglai;Xiao Cong;Long Nengji;Liu Lijuan(Department of Bone,Third Hospital of Mianyang,Sichuan Mental Health Center,Mianyang 621000,China)

机构地区：[1]四川省绵阳市第三人民医院四川省精神卫生中心骨科,绵阳621000

出　　处：《广西医科大学学报》2022年第1期67-73,共7页Journal of Guangxi Medical University

基　　金：四川省医学会课题项目资助(No.2020SAT46)。

摘　　要：目的:研究局部注射银杏叶提取物注射液对糖尿病足溃疡(DFU)模型大鼠创面愈合的作用及其机制。方法:取48只健康雄性SD大鼠,其中24只采用高糖高脂饲料喂养和腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型,并于足背部切除面积约为1 cm×1 cm的全层皮肤组织建立DFU模型,随机分为DFU组、DFU+术前术后注射组和DFU+术后注射组。剩余24只大鼠仅在相同位置作溃疡创面,随机分为普通溃疡组、普通溃疡+术前术后注射组、普通溃疡+术后注射组。术前术后注射组于皮肤缺损术前2 d至术后21 d在创面局部注射银杏叶提取物注射液,术后注射组在术后第1天开始注射银杏叶提取物注射液,连续21 d。比较各组创面愈合率。通过CD34免疫组化染色观察创面组织微血管密度(MVD)。采用酶联免疫吸附试验(ELISA)法检测创面组织肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6、IL-8、丙二醛(MDA)和超氧化物歧化酶(SOD)水平。Western blotting法检测Wnt1、Wnt3a、β-catenin蛋白表达。结果:与普通溃疡组比较,DFU组术后1周、3周创面愈合率,创面组织MVD、SOD水平和Wnt1、Wnt3α、β-catenin蛋白表达量均明显降低,MDA、TNF-α、IL-6、IL-8含量显著升高(均P<0.05)。与DFU组比较,DFU+术前术后注射组术后1周、2周创面愈合率,创面组织MVD、SOD水平及Wnt1、Wnt3a、β-catenin蛋白表达明显升高,TNF-α、IL-6、IL-8和MDA含量明显降低(均P<0.05)。结论:术前术后注射银杏叶提取物注射液可激活DFU大鼠Wnt/β-catenin信号通路,改善炎症和氧化应激反应,促进创口微血管再生,提高创面愈合率。Objective:To observe the therapeutic effect of local injection of Ginkgo biloba extract on wound healing in rats with diabetic foot ulcer(DFU)model and its mechanism.Methods:48 healthy male SD rats were selected,and 24 of which were fed with high sugar and high fat diet and intraperitoneally injected with streptozotocin(STZ)to establish diabetic rat models.A full layer of skin tissue with an area of 1 cm×1 cm was excised from the back of the foot to establish a DFU model,which were randomly divided into DFU group,DFU+preoperative and postoperative injection group and DFU+postoperative injection group.The remaining 24 rats were made ulcerated wounds at the same location and were randomly divided into common ulcer group,common ulcer+preoperative postoperative injection group,and common ulcer+postoperative injection group.The preoperative-postoperative injection group wasgiven Ginkgo biloba extract injection locally on the wound surface from 2 d before to 21 d after skin defect surgery,and the postoperative injection group was given Ginkgo biloba extract injection from the first day after surgery for 21 d.The wound healing rate of each group was compared.The microvascular density(MVD)of the traumatic tissue was observed by CD34 immunohistochemical staining.The levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-8,malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent assay(ELISA).The expressions of Wnt1,Wnt3a andβ-catenin protein were measured by western blotting.Results:Compared with the normal ulcer group,the ulcer healing rate at the1st and 3rd week,MVD,SOD activity and Wnt1,Wnt3α,β-catenin protein expressionsin wound tissues were significantly lower and the levels of MDA,TNF-α,IL-6 and IL-8 levels were significantly higher in the DFU group(P<0.05).Compared with the DFU group,the wound healing rate at the1st and 2nd week,MVD,SOD activity and Wnt1,Wnt3a,β-catenin protein expressions were significantly higher and the levels of TNF-α,IL-6,IL-8 and MDA in wound t

关 键 词：银杏叶提取物注射液 糖尿病足 氧化应激 炎性因子 WNT/Β-CATENIN信号通路 微血管密度 

分 类 号：R965.4[医药卫生—药理学]