关键词: 罗格列酮, 增生性瘢痕, 兔耳模型, 纤维化, 过氧化物酶体增殖物激活受体γ(PPARγ)

Abstract: Objective To investigate the inhibitory effect of peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone (RSG) on hypertrophic scars of rabbit ears and potential mechanism. Methods Sixteen hypertrophic scar model rabbits were established with 8 adult New Zealand white rabbits. Randomly, 2 rabbits (4 scars in total) were selected for comparative verification with normal rabbit ear skin to verify the successful establishment of the scar model. Remaining 12 scars were randomly divided into two groups: the phosphate baffer saline(PBS) control group (local injection of 1 mL, PBS, n=6) and the RSG group (local injection of 1 mL PBS suspension containing 10 mg RSG, n=6).After the intervention, the changes in the appearance of scars of both groups were observed. Additionally, HE staining and Masson staining were performed to examine the tissue structure, immunohistochemistry was used to detect α-smooth muscle actin (α-SMA), and Q-PCR was used to detect the expression of fibrosis markers type Ⅰ collagen (Col Ⅰ), type Ⅲ collagen (Col Ⅲ), α-SMA, transforming growth factor-β1 (TGF-β1)and adipogenic signaling molecules CCAAT/enhancer-binding protein α(C/EBPα) and PPARγ mRNA. Results Compared with normal rabbit ear skin, red, elevated, and firm hypertrophic scars were observed in the modeled areas. HE staining showed that the dermal thickness of rabbit ear scars was significantly greater than that of normal rabbit ear skin(P＜0.05). Results at each time point after intervention showed that, compared with the PBS control group, the scars in the RSG group became flatter, narrower, and softer in texture. HE and Masson staining demonstrated that the RSG group exhibited clearer skin structure, thinner dermis, reduced collagen deposition with regular arrangement, and the presence of newly formed adipocytes. Immuno-histochemistry showed a decreased expression of α-SMA in the RSG group (P＜0.05). Additionally, mRNA expression of ColⅠ, Col Ⅲ, α-SMA, and TGF-β1 was down-regulated, while the mRNA expression of C/EBPα and PPARγ was up-regulated in the RSG group (P＜0.05). Conclusions Rosiglitazone can effectively inhibit the formation of hypertrophic scars in rabbit ears. Its mechanism may involve down-regulation of fibrosis markers expression while up-regulation of adipogenic signals, thereby promotes formation of new adipocytes. This finding provides a new evidence to support clinical treatment of hypertrophic scars.

Key words: rosiglitazone, hypertrophic scar, rabbit ear model, fibrosis, peroxisome proliferator-activated receptor-γ(PPARγ)