本文選題：疤痕　切入點：吡非尼酮　出處：《中國人民解放軍醫(yī)學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：吡非尼酮是一種具有抗纖維化功能的藥物,目前主要用于特發(fā)性肺纖維化的治療。其主要的作用機制為抗纖維化、抗炎及抗氧化。其中,抗纖維化作用是通過抑制或調(diào)控TGF-β、IL-1β、CTGF、α-SMA、PDGF等信號分子的產(chǎn)生來實現(xiàn)。增生性瘢痕是皮膚科的常見病,大量研究表明其發(fā)病機制可能與TGF-β/Smad通路異常有關(guān)。因此,我們提出設(shè)想:吡非尼酮能夠抑制瘢痕的增生嗎?目的建立兔耳瘢痕模型,探究口服或外用吡非尼酮對兔耳增生性瘢痕的影響,并對其作用機制進行初步探究,研究吡非尼酮對兔耳瘢痕模型中TGF-β/Smad通路的影響。方法將20只日本大耳白兔(2.0～2.5kg)隨機分為四組,A、B、C三組建立兔耳增生性瘢痕模型。14天后,待創(chuàng)面基本實現(xiàn)上皮化,A組予0.5%吡非尼酮與食物混合飼養(yǎng);B組予8%吡非尼酮軟膏外用;C組為瘢痕對照;D組為正常皮膚對照(不做任何處理)。造模2月后分別測量瘢痕厚度,處死實驗動物并對瘢痕組織/正常皮膚標(biāo)本進行HE染色、Masson染色,了解各組瘢痕組織的病理學(xué)改變。最后,采用Western-blot的方法檢測兔耳增生瘢痕組織中TGF-β1, Smad2, Smad3, Smad4蛋白表達情況。結(jié)果口服吡非尼酮組(A組)瘢痕平均厚度為1.79±0.32cm,外用吡非尼酮組(B組)瘢痕平均厚度為1.95±0.39cm,瘢痕對照組(C組)瘢痕平均厚度為1.99±0.43cm, A組小于B,C組,差異有統(tǒng)計學(xué)意義(P0.05); HE染色、Masson染色可見A組膠原結(jié)構(gòu)排列較B、C組疏松。Western-blot結(jié)果顯示口服吡非尼酮組TGF-β1, Smad2,Smad3, Smad4表達均低于瘢痕對照組,外用吡非尼酮組TGF-β1, Smad2, Smad3,Smad4表達量下降程度不及口服吡非尼酮組。結(jié)論口服吡非尼酮對兔耳增生性瘢痕有一定的抑制作用,外用8%吡非尼酮效果不顯著。在口服吡非尼酮組兔耳增生性瘢痕組織中,TGF-β1,Smad2,Smad3,Smad4蛋白表達均下降,說明口服吡非尼酮抑制兔耳瘢痕增生可能通過TGF-β/Smad通路實現(xiàn),即通過抑制TGF-β1表達,下調(diào)Smad2, Smad3, Smad4的表達,從而抑制膠原的增生。
[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 偽 -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 鹵0.32 cm in pifenidone group, 1.95 鹵0.39 cm in pifenidone group and 1.95 鹵0.39 cm in control group. The mean thickness of scar in group C was 1.99 鹵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.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R622;R-332

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本文編號：1624052