Efficacy of antimicrobial peptide LL-37 and derivative peptides in diabetic wound healing
Objective To investigate the effects of LL-37 and its derivative peptides LL-37R on diabetic wound healing.Methods The mouse embryonic fibroblast cell lines(NIH/3T3)and human um-bilical vein endothelial cells(HUVECs)were cultured under high glucose conditions.Cell compatibility of LL-37 and LL-37 R was evaluated using live/dead staining and cell counting kit(CCK-8)assay,and their effects on the proliferation and migration of HUVECs were assessed through scratch and tube formation as-says.A total of 36 male SD rats were selected and randomly divided into control,LL-37,and LL-37R groups,with 12 rats in each group.Diabetic wound models were created by making a 2 cm diameter full-thickness skin lesion on the back.Physiological saline,LL-37,or LL-37R was injected subcutaneously ev-ery 2 days.Wound photographs were taken on days 0,3,7,14,and 21.On day 21,tissues were collect-ed for hematoxylin-eosin(HE)staining,Masson's trichrome staining,and immunohistochemistry staining to evaluate wound healing.Data were analyzed using ANOVA and unpaired t-tests.Results LL-37R alle-viated cell damage in NIH/3T3 and HUVEC cells under high glucose conditions and promoted HUVECs migration and angiogenesis.For diabetic wounds in rats,the mean wound area proportions of the LL-37 and LL-37R groups were(31.46±5.51)％and(18.01±4.29)％of the initial wound at 21st day post-model-ing,respectively,significantly smaller than the control group[(41.10±4.54)％,t=3.01,2.83,P＜0.05].HE staining revealed a significant increase in epidermal thickness for LL-37 and LL-37R groups[(73.06±17.67),(70.35±4.60)μm,respectively]compared to the control group[(26.94±11.61)μm,t=2.18,3.48,P＜0.05].Masson's trichrome staining showed more organized and dense colla-gen fiber arrangement in the LL-37R group(F=78.61,P＜0.01).Immunohistochemical staining results showed that the CD31 positive vascular density in the LL-37R group was(221.62±18.69)vessels/mm2,significantly greater than in the control group[(100.38±11.94)vessels/mm2]and LL-37 group[(117.95±16.01)vessels/mm2,F=17.02,P＜0.01].In addition,the LL-37R group demonstrated a markedly lower count of CD86-positive inflammatory macrophages in the wound area,with(20.18±5.08)cells/mm2,than the LL-37 group[(61.82±8.101)cells/mm2]and the control group[(236.00±17.89)cells/mm2,F=95.59,P＜0.01].Conclusion LL-37 and its derivative peptide LL-37R can accelerate the healing of diabetic wounds by promoting vascular regeneration,collagen deposition,and inflammation regulation.
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