Exploring the Effect of Shaobei Injection on Rabbit Ear Hypertrophic Scars Based on TGF-β1/Smads Signaling Pathway

FENG Yuening; SHEN Yuhang; FENG Dayong; WANG Chunhui; BAI Zhiyong; WANG Qian; WANG Jingwen; AN Ayue

Abstract：Objective To explore the effects of Shaobei Injection on TGF-β1/Smads signaling pathway of hypertrophic scar(HS)in rabbit ears and discuss the mechanism of Shaobei Injection.Methods Twenty New Zealand white rabbits were randomly divided into a normal group,a model group,a Shaobei group,and a triamcinolone acetonide group.Except for the normal group,the rabbit ear HS model was prepared by establishing a 10 mm diameter full-thickness skin wound in the other groups,and the corresponding drugs were injected into the scar tissue once every 7 days for 2 weeks.The general changes of scar tissue in each group were observed by skin microscopy.The distribution of collagen fiber in scar tissue was observed by two-photon microscopy.The pathological changes of scar tissue in rabbit ears were observed by HE staining.Concentrations of IL-1β,IL-6 and TNF-α were detected by ELISA.The protein and mRNA expressions of TGF-β1,Smad2,Smad3 and Smad7 were detected by Western blot and RT-qPCR.Results Compared with the normal group,the thickness of rabbit ear HS in the model group was significantly increased(P<0.01),and was higher than the epidermis with dark red color and hard texture.Blood vessels proliferated significantly,forming inflammatory granulation tissue,and collagen fibers were arranged in directional strips.The density of fibroblasts in HS tissue increased significantly(P<0.01),the contents of IL-1β,IL-6,and TNF-α increased dramatically(P<0.01),and TGF-β1,Smad2,Smad3 protein and mRNA expression increased significantly(P<0.01),while the expression of Smad7 protein and mRNA decreased significantly(P<0.01).Compared with the model group,the HS hyperplasia condition of rabbit ears in the Shaobei group was significantly improved,the density of fibroblasts in the HS tissue was reduced(P<0.05),and the contents of IL-1β,IL-6,and TNF-α were significantly reduced(P<0.01).The expressions of TGF-β1,Smad2,Smad3 proteins and mRNA were significantly reduced(P<0.01).Shaobei Injection showed superior effects compared to the triamcinolone in improving HS,reducing TNF-α levels,decreasing the protein and mRNA expressions of TGF-β1,Smad2,and Smad3(P<0.05).Conclusion Shaobei Injection can inhibit the formation of HS by inhibiting angiogenesis and inflammatory response in scar tissue,and its mechanism may be related to downregulating TGF-β1/Smads signaling pathway.