Experimental study on the effects of shikonin on iNOS/COX-2 inflammatory pathway in rat random flaps / 中华整形外科杂志

ABSTRACT

Objective@#To investigate the effects and the potential mechanism of shikonin on rat random flaps.@*Methods@#Seventy-two wistar male rats in grade SPF were randomly divided into negative control group, tetramethylpyrazine group (TMP group) or shikonin treatment group. The random skin flap sized 8 cm×2 cm, with a cephalic based pedicle, was performed on the back of the rat. Each group was administered accordingly by intraperitoneal injection once per day for 7 days shikonin treatment group (1 mg/kg), TMP group (10 mg/kg) and control group (1 ml/kg). Morphological changes of skin flaps were observed by HE staining. The positive expression of iNOS and COX-2 in skin flap tissues after operation were detected by immunofluorescence staining. The serum contents of TNF-α and IL-6 were detected by ELISA.@*Results@#Inflammatory cell infiltration and inflammatory reaction of flap was more severe in control group at different time points after operation. The number of inflammatory cells in shikonin treatment group and TMP group were significantly decreased, compared with controls (P<0.01). The decrease of the inflammatory cell numbers in shikonin treatment group was more significant. The proliferation of granulation tissue and fibroblast in skin flap was obvious, and the survival rates of the skin flap were significantly increased in shikonin treatment group and TMP group (both P<0.01). The numbers of iNOS or COX-2 positive cells in shikonin treatment group and TMP group were significantly decreased, when compared with controls (both P<0.01). Compared with TMP group, the numbers of iNOS and COX-2 positive cells in shikonin treatment group were significantly decreased (P<0.01 and P<0.05, respectively)in early period after operation. Compared with the control group, serum levels of TNF-α and IL-6 in shikonin treatment group and TMP group were significantly decreased (all P<0.01). The shikonin treatment group developed more significant reduce.@*Conclusions@#Shikonin can significantly improve inflammatory response of skin flap in rats, which might be related to inhibiting the expression of iNOS and COX-2, decreasing serum levels of TNF-α and IL-6 , and reducing the release of inflammatory cytokines .