吡非尼酮不同给药方式抑制兔耳增生性瘢痕的实验研究

发布时间：2018-03-17 09:03

本文选题：疤痕　切入点：吡非尼酮　出处：《中国人民解放军医学院》2017年硕士论文　论文类型：学位论文

【摘要】：吡非尼酮是一种具有抗纤维化功能的药物,目前主要用于特发性肺纤维化的治疗。其主要的作用机制为抗纤维化、抗炎及抗氧化。其中,抗纤维化作用是通过抑制或调控TGF-β、IL-1β、CTGF、α-SMA、PDGF等信号分子的产生来实现。增生性瘢痕是皮肤科的常见病,大量研究表明其发病机制可能与TGF-β/Smad通路异常有关。因此,我们提出设想:吡非尼酮能够抑制瘢痕的增生吗?目的建立兔耳瘢痕模型,探究口服或外用吡非尼酮对兔耳增生性瘢痕的影响,并对其作用机制进行初步探究,研究吡非尼酮对兔耳瘢痕模型中TGF-β/Smad通路的影响。方法将20只日本大耳白兔(2.0～2.5kg)随机分为四组,A、B、C三组建立兔耳增生性瘢痕模型。14天后,待创面基本实现上皮化,A组予0.5%吡非尼酮与食物混合饲养;B组予8%吡非尼酮软膏外用;C组为瘢痕对照;D组为正常皮肤对照(不做任何处理)。造模2月后分别测量瘢痕厚度,处死实验动物并对瘢痕组织/正常皮肤标本进行HE染色、Masson染色,了解各组瘢痕组织的病理学改变。最后,采用Western-blot的方法检测兔耳增生瘢痕组织中TGF-β1, Smad2, Smad3, Smad4蛋白表达情况。结果口服吡非尼酮组(A组)瘢痕平均厚度为1.79±0.32cm,外用吡非尼酮组(B组)瘢痕平均厚度为1.95±0.39cm,瘢痕对照组(C组)瘢痕平均厚度为1.99±0.43cm, A组小于B,C组,差异有统计学意义(P0.05); HE染色、Masson染色可见A组胶原结构排列较B、C组疏松。Western-blot结果显示口服吡非尼酮组TGF-β1, Smad2,Smad3, Smad4表达均低于瘢痕对照组,外用吡非尼酮组TGF-β1, Smad2, Smad3,Smad4表达量下降程度不及口服吡非尼酮组。结论口服吡非尼酮对兔耳增生性瘢痕有一定的抑制作用,外用8%吡非尼酮效果不显著。在口服吡非尼酮组兔耳增生性瘢痕组织中,TGF-β1,Smad2,Smad3,Smad4蛋白表达均下降,说明口服吡非尼酮抑制兔耳瘢痕增生可能通过TGF-β/Smad通路实现,即通过抑制TGF-β1表达,下调Smad2, Smad3, Smad4的表达,从而抑制胶原的增生。
[Abstract]:Pifenidone is an anti-fibrosis drug, which is mainly used in the treatment of idiopathic pulmonary fibrosis. Its main mechanisms are anti-fibrosis, anti-inflammation and anti-oxidation. The anti-fibrosis effect is realized by inhibiting or regulating the production of signal molecules such as TGF- 尾 IL-1 尾 -CTGFand 伪 -SMA-PDGF. Hypertrophic scar is a common disease in dermatology. A lot of studies have shown that its pathogenesis may be related to the abnormal TGF- 尾 / Smad pathway. We suggest that pifenidone can inhibit scar proliferation? Objective to establish rabbit ear scar model and explore the effect of pifenidone on hypertrophic scar and its mechanism. To study the effect of pifenidone on TGF- 尾 / Smad pathway in rabbit ear scar model. Methods Twenty Japanese white rabbits were randomly divided into four groups. When the wound was basically epithelialized, group A was treated with 0.5% pipefenidone and food mixed feeding, group B was treated with 8% pipefenidone ointment, and group C was treated as scar control group D as normal skin control (without any treatment). Scar thickness was measured after modeling on February. The experimental animals were killed and the scar tissue / normal skin specimens were stained with HE staining and Masson staining to understand the pathological changes of scar tissue in each group. The expression of TGF- 尾 1, Smad2, Smad3 and Smad4 protein in rabbit ear hypertrophic scar tissue was detected by Western-blot method. Results the mean thickness of scar was 1.79 卤0.32 cm in pifenidone group, 1.95 卤0.39 cm in pifenidone group and 1.95 卤0.39 cm in control group. The mean thickness of scar in group C was 1.99 卤0.43 cm, and that in group A was smaller than that in group B (P < 0.05). The results of HE staining and Masson staining showed that the structure of collagen in group A was lower than that in group B and C, and the expression of TGF- 尾 1, Smad2, Smad3 and Smad4 in group A was lower than that in group B and C, and the expression of TGF- 尾 1, Smad2 and Smad3 in group A was lower than that in group B and C. The expression of TGF- 尾 1, Smad2, Smad3 and Smad4 in pifenidone group was lower than that in pifenidone group. Conclusion pifenidone has a certain inhibitory effect on hypertrophic scar in rabbit ear. The expression of TGF- 尾 1, Smad2, Smad3, Smad4 protein in rabbit ear hypertrophic scar tissue was decreased, which indicated that the inhibition of hypertrophic scar proliferation by pifenidone might be achieved through TGF- 尾 / Smad pathway, that is, by inhibiting the expression of TGF- 尾 1, the expression of TGF- 尾 1 in rabbit ear hypertrophic scar tissue was decreased. The expression of Smad2, Smad3 and Smad4 was down-regulated, which inhibited the proliferation of collagen.
【学位授予单位】：中国人民解放军医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R622;R-332

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