Effect of Dihydroartemisinin on the Inflammatory Response and Skin Wound Healing in Diabetic Rats
Objective To investigate the effect of dihydroartemisinin(DHA)on the inflammatory response and skin wound healing in diabetic rats.Methods The ointment was prepared with Carbomer 980,Tween-80,glycerol,ultrapure water and sodium hydroxide as a base.DHA and ethyl nipagin were added and stirred evenly,resulting in DHA ointment.Fifty SPF-grade SD rats were used to create a diabetic rat model by intraperitoneal injection of streptozotocin,and 44 rats were successfully modelled.Whole skin defect wounds were created on the back of rats by using a 2.0 cm diameter circular punch.Thirty-six dorsal wounds were randomly divided into 4 groups(n=9)by the random number table.Then the wounds were applied respectively with 5%DHA,10%DHA,15%DHA and ointment base(control group)once a day for 14 consecutive days.On the 3th,7th and 14th days,the wound healing was observed,the specimens were cut from 0.2 cm of wound margin and would tissue,the histological changes were observed by HE staining.Collagen changes were observed by Masson staining,and the concentrations of interleukin 6(IL-6),interleukin 10(IL-10),and tumor necrosis factor-α(TNF-α)were detected by ELISA.The other eight rats were randomly divided into 10%DHA group and control group.The tissue was cut from the wound on the 7th day,and transcriptome sequencing was performed by high-throughput sequencing technology to screen the differentially expressed genes(DEGs)between the two groups.Gene ontology(GO)functional enrichment analysis as well as kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis were performed.Data were analyzed by one-way ANOVA using SPSS 27.0 statistical software.Results The different concentrations of DHA groups showed better wound healing rates than the control group.The 10%DHA group has the most significant effect(P＜0.05).Compared with the control group,each DHA group showed a decrease in inflammatory cell infiltration and an increase in collagen fibre area on the 7th and 14th days(P＜0.05).The expressions of IL-6 and TNF-α in each DHA group were significantly lower than those in the control group(P＜0.05),while the expression of IL-10 was significantly higher than that in the control group(P＜0.05).Differential gene volcano map showed that the 10%DHA group remarkably up-regulated anti-inflammatory and antibacterial genes such as hypoxia inducible factor 1α(Hif-1α),Smad homolog 12(Smad12)and β-defensin 4(Defb4).The GO functional enrichment analysis indicated that the 10%DHA group was significantly enriched in inflammatory response,immune response and defense response to bacterium.The KEGG enrichment analysis showed that the 10%DHA group was significantly enriched in chemokine signaling pathway,NOD-like receptor signaling pathway and so on.Conclusion DHA may inhibit excessive inflammatory responses by modulating inflammatory factors,anti-inflammatory and antimicrobial genes,chemokine signaling pathway and NOD-like receptor signaling pathway as well as reducing inflammatory cell infiltration,thereby enhancing wound healing.
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