Therapeutic Effects Of Different Administrations Of Pirfenidone In Pathological Scar On Rabbit's Ears

Pirfenidone is a drug with anti-fibrosis function, which is mainly used for the treatment of idiopathic pulmonary fibrosis clinically. The functional mechanism of pirfenidone includesanti-fibrosis, anti-inflammatory and anti-oxidation. The anti-fibrosis function is achieved by inhibiting or regulating the production of signal molecules such as TGF-?,IL-1?, CTGF,a-SMA, PDGF. Hypertrophic scar is a common disease in dermatology, and many studies have shown that the pathogenesis might be related to the abnormality of TGF-?/Smad pathway. Therefore, we raise the scientific question: does pirfenidone inhibit scarring?ObjectiveTo establish rabbit ear scar model and explore the therapeutic effect of oral or topical administration of pirfenidoneas an inhibitor of hypertrophic scar; to explore its mechanism of action by measuring the effect of pirfenidone on TGF-?/Smad pathway in rabbit ear scar model.MethodA total of 20 Japanese white rabbits(2.0?2.5kg) were included and randomly divided into 4 groups. Animal model of hypertrophic scars on group A, group B and group C. Fourteen days after surgery, group A were fed with 0.5% pirfenidone powder mixed with food; Group B were treated with 8%pirfenidone ointment topically; Group C served aspositive control and group D were the negative control. Two months after the surgery, hypertrophic scars were measured. Hematoxylin and eosin (HE)and Masson's trichrome staining were performed. The expressions of TGF-?1, Smad2, Smad3, and Smad4 were detected in hypertrophic scar tissues of rabbit ear by western-blot.ResultThe average thicknesses of hypertrophic scars of group A, B, C are 1.79�0.32cm, 1.95�0.39cm and 1.99�0.43cm respectively.The scar of group A were significantly thinner than that of group B and group C (P<0.05). HE and Masson's trichrome staining also showed reduced collagen content in group A. Western-blot presented that the expression of TGF-?1, Smad2,Smad3, Smad4 were remarkably down-regulated in group A, while no similar change was found in group B.ConclusionOral administration ofpirfenidone carries an effect of inhibiting hypertrophic scar of rabbit's ear in some extent, while topical administration of 8% pirfenidone does not work significantly. In oral administration group,the expression of TGF-?1, Smad2, Smad3 and Smad4 in the hypertrophic scar tissue of the rabbits decreased, which indicated that oral administration of pirfenidone could inhibit the proliferation of rabbit ear hypertrophy through TGF-(3/Smad pathway, That is, by inhibiting the expression of TGF-?1,down-regulation of Smad2, Smad3, Smad4 expression, and thereby inhibiting collagen proliferation.