重组人表皮生长因子联合前列地尔对糖尿病溃疡大鼠Wnt/β-连环素信号通路表达的影响

Effect of recombined human epidermal growth factor combined with alprostadil on Wnt/β-catenin signal pathway in rats with diabetic ulcer

目的探讨重组人表皮生长因子(rhEGF)联合前列地尔对糖尿病溃疡Wnt/β-连环素(β-Catenin)信号通路的作用。方法糖尿病皮肤溃疡大鼠模型随机分为4组。对照组注射用生理盐水冲洗创面;rhEGF组rhEGF凝胶涂抹创面;前列地尔组尾静脉推注前列地尔;联合给药组同时予rhEGF和注射用前列地尔治疗。观察各组皮肤愈合情况,治疗后第14天测溃疡创面Wnt-1、β-Catenin、糖原合成酶激酶-3(GSK-3β)mRNA和蛋白的表达。结果给药后第6、10和14天时联合给药组溃疡面愈合率为(9.76±2.37)%、(35.74±3.65)%、(51.37±4.16)%及(84.42±5.35)%,均较rhEGF组和前列地尔组增加(P<0.05);给药后14d时联合给药组溃疡面Wnt-1、β-Catenin和GSK-3βmRNA表达分别为(1.42±0.19)、(1.56±0.21)和(0.95±0.15),均较rhEGF组和前列地尔组增加(P<0.05);给药后14d时联合给药组溃疡面Wnt-1、β-Catenin和GSK-3β蛋白的表达分别为(1.17±0.16)、(1.38±0.18)和(0.81±0.13),均较rhEGF组和前列地尔组增加(P<0.05)。结论 rhEGF联合前列地尔可促进糖尿病溃疡的愈合,并通过上调Wnt-1、β-Catenin和GSK-3β的表达而起到调节Wnt/β-Catenin信号通路的功能。

Objective To explore the effect of recombined Human epidermal growth factor（rhEG）combined with alprostadilon Wnt/β-Catenin signal pathway in rats with diabetic ulcer. Methods Rats with diabetic ulcer were randomly divided into four groups：control group,rhEG group,epidermal group and combined treatment group.Ulcer skin was smeared by normalsaline in control group,and by rhEG in rhEG group.Epidermal was administered from caudal vein in epidermal group.Combined treatment group was treated by rhEG and epidermal at the same time.The healing status were observed.The proteinand mRNA expression of Wnt-1,β-Catenin and GSK-3βwere measured 14 days after treatment. ResultsThe healing rates in combined treatment group were（9.76±2.37）%,（35.74±3.65）%,（51.37±4.16）% and（84.42±5.35）% respectivelyin 6th,10th and 14th day after treatment,which were significantly higher than in rhEG group and epidermal group（P〈0.05）.The mRNA levels of Wnt-1,β-Catenin and GSK-3βin combined treatment group were（1.42±0.19）,（1.56±0.21）and（0.95±0.15）after treatment for 14 days,which were significantly higher than in rhEG group and epidermal group（P〈0.05）.Protein levels of Wnt-1,β-Catenin and GSK-3βin combined treatment group were（1.17±0.16）,（1.38±0.18）and（0.81±0.13）after treatment for 14 days,which were significantly higher than in rhEG group and epidermal group（P 〈0.05）. Conclusion rhEG combined with epidermal can significantly accelerate the healing of diabetic ulcer,and can regulatethe Wnt/β-Catenin signal pathway by increasing the expression of Wnt-1,β-Catenin and GSK-3β.