基于Notch信号通路探讨矾冰纳米乳对增生性瘢痕的影响

Effects of alum ice nanoemulsion on hypertrophic scar based on Notch signaling pathway

目的基于Notch信号通路探讨矾冰纳米乳对增生性瘢痕模型大鼠VEGF、TGF-β1的影响。方法将144只SD大鼠按照随机数字表法分为空白对照组、模型组、曲安奈德组及矾冰纳米乳组低、中、高剂量组,每组24只。除空白对照组外,其余各组大鼠制备深Ⅱ°烧伤增生性瘢痕模型。造模成功后24 h,模型组给予等量生理盐水外涂,矾冰纳米乳组低、中、高剂量组大鼠分别外涂矾冰纳米乳8.15、6.30、32.60 mg/ml,曲安奈德组外涂曲安奈德,2次/d,每次0.2 ml,连续给药35 d。分别在第14、21、28、35天,采用VG染色计算胶原纤维面密度;采用Western blot检测VEGF、TGF-β1、Notch1、Jagged1蛋白表达;采用RT-PCR检测Notch1、Jagged1 mRNA表达。结果与模型组比较,曲安奈德组与矾冰纳米乳各剂量组胶原纤维面密度降低(P<0.05),VEGF、TGF-β1、Notch1、Jagged1蛋白及Notch1、Jagged1 mRNA水平降低(P<0.05)。与曲安奈德组比较,中剂量组胶原纤维面密度、VEGF、TGF-β1、Notch1、Jagged1蛋白及Notch1、Jagged1 mRNA水平降低(P<0.05)。结论矾冰纳米乳抑制增生性瘢痕形成的作用机制与下调Notch信号通路相关分子Notch1、Jagged1蛋白及mRNA水平,进而下调VEGF、TGF-β1蛋白表达有关。

Objective To investigate the effects of alum ice nanoemulsion on VEGF and TGF-β1 in hypertrophic scar based on Notch signaling pathway.Methods Totally 144 SD rats were divided into blank control group,model group,triamcinolone acetonide group and alum ice nanoemulsion low-,medium-and high-dose groups according to random number table method,with 24 rats in each group.Except for the blank control group,the rats in other groups were prepared with deepⅡ°burn models.24 hours after the successful modeling,the model group was given the same amount of normal saline,the rats in alum ice nanoemulsion low-,medium-and high-dose groups were given 8.15,6.30 and 32.60 mg/ml alum ice nanoemulsion respectively,and the triamcinolone acetonide group was given triamcinolone acetonide twice a day,0.2 ml each time,for 35 consecutive days.At 14,21,28 and 35 d,the collagen fiber surface density was calculated by VG staining.The protein expressions of vascular endothelial growth factor(VEGF),transforming growth factor-β1(TGF-β1),Notch1 and Jagged1 were detected by Western Blot.The expressions of Notch1 mRNA and Jagged1 mRNA were detected by RT-PCR.Results Compared with model group,triamcinolone acetonide and different doses of alum ice nanoemulsion groups could decrease collagen fiber surface density,protein expressions of VEGF,TGF-β1,Notch1,Jagged1 and mRNA expressions of Notch1,Jagged1 in different degrees(P<0.05).Compared with the triamcinolone acetonide group,the collagen fiber surface density,protein expressions of VEGF,TGF-β1,Notch1 and Jagged1 and mRNA expressions of Notch1,Jagged1 in the alum ice nanoemulsion medium-dosage group decreased(P<0.05).Conclusion Alum ice nanoemulsion can inhibit hypertrophic scar formation,and its mechanism is related to down-regulating Notch signal pathway related molecules Notch1,Jagged1 protein and mRNA levels,and then down-regulating VEGF and TGF-β1 protein expressions.