Promotion of Wound Healing in Diabetic Mice by Transdermal Administration of Chiglitazar
Objective To investigate the extent to which peroxisome proliferator-activated receptors panagonist chiglitazar can promote wound healing in diabetic mice.Methods Hyperglycemic medium or lipopolysaccharide was used to simulate the high glucose and inflammatory cell environment of diabetic patients.The improvement of RAW 264.7 function of damaged macrophages by chiglitazar in a high glucose or inflammatory environment was verified at the cellular level via CCK-8 assay and nitric oxide level detection.Effects on the proliferation and migration of high-glucose induced keratinocyte HaCaT were quantified via cell counting assay and cell scratch assay.The effect of chiglitazar hydrogel on diabetic wound healing was confirmed in a wound model of diabetic mice by screening suitable in vivo dose concen-trations.Results In the macrophage experiment,the high glucose environment inhibited the activity of RAW 264.7 compared with control group.Compared with high glucose group,chiglitazar 1.6,3.2 μg·ml-1 ameliorated the inhibitory effect of high glucose on macrophages'proliferative activity and promoted the transition from pro-inflammatory to anti-inflammatory type of macrophages(P<0.01).In the skin cell experiment,chiglitazar 6.4 μg·ml-1 promoted the proliferation and migration of HaCaT under the high glucose environment(P<0.05)compared with high glucose group.In the in vivo experi-ment,chiglitazar hydrogel promoted wound healing in diabetic mice(P<0.05).Conclusion As a peroxi-some proliferator-activated receptors pan-agonist,chiglitazar could promote wound healing by inhibiting chronic inflammation and promoting keratinocyte proliferation and migration.
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