丹参酮ⅡA-丹酚酸B共载脂质体自溶性微针对烧烫伤大鼠瘢痕增生的抑制作用及机制OA

Objective To investigate the inhibitory effect and mechanism of Tanshinone ⅡA-Salvianolic acid B co-loaded liposome self-dissolving microneedles(TSA-SAB Lips@DMN)on scar hyperplasia in burn rats.Methods TSA-SAB Lips@DMN was prepared by a casting method.A rat model of hypertrophic scar was established using a burn method.Female SD rats with successful modeling were randomly divided into the model group,positive drug group,and TSA-SAB Lips@DMN low-,medium-,and high-dose groups,with 9 rats in each group.An additional 9 rats were randomly selected as the normal group.The normal and model groups received no drug intervention(application of normal saline).The positive drug group was topically treated with asiaticoside cream(total asiaticoside content 2.5％,approximately 4 cm2 per application).The TSA-SAB Lips@DMN low-,medium-,and high-dose groups received daily microneedle patches with Tanshinone ⅡA and Salvianolic Acid B contents of[(216.01±1.96),(371.65±4.23)μg],[(432.02±3.92),(743.30±8.46)μg],and[(648.03±5.88),(1 114.95±12.69)μg],respectively,for 14 consecutive days.Serum levels of transforming growth factor-β1(TGF-β1)and Smad3,as well as the contents of type I collagen(COL-I)and type Ⅲ collagen(COL-Ⅲ)in scar tissue,were measured by ELISA.Pathological changes in rat scar tissue were observed by HE and Masson staining.The expression level of vascular endothelial growth factor(VEGF)protein in scar tissue was detected by immunohistochemistry.Results Compared with the normal group,the model group showed a significant increase in fibroblast number,marked thickening of the epidermal spinous and granular cell layers,disordered cell arrangement,a significantly increased scar hyperplasia index(P<0.05),and a significantly increased area density of collagen fibers(P<0.05),indicating successful replication of the hypertrophic scar rat model.Serum levels of TGF-β1 and Smad3 were significantly elevated(P<0.05).The contents of COL-Ⅰ and COL-Ⅲ in scar tissue were significantly increased(P<0.05),and VEGF expression was significantly upregulated(P<0.05).Compared with the model group,all treatment groups showed significantly reduced serum levels of TGF-β1 and Smad3(P<0.05),a significantly decreased scar hyperplasia index(P<0.05),a significantly reduced area density of collagen fibers(P<0.05),and significantly downregulated VEGF protein expression in scar tissue(P<0.05).The contents of COL-Ⅰ and COL-Ⅲ in scar tissue were significantly decreased in the positive drug group and the TSA-SAB Lips@DMN medium-and high-dose groups(P<0.05).Conclusion TSA-SAB Lips@DMN significantly inhibits skin hypertrophic scar formation in burn rats,which may be related to the regulation of the TGF-β/Smad pathway and VEGF protein expression.