芹菜素对糖尿病大鼠足创面愈合的影响

Effect of Apigenin on Foot Wound Healing in Diabetic Rats

目的:探讨芹菜素是否能通过减少炎症反应、促进血管与组织形成,帮助糖尿病足大鼠创面快速愈合。方法:SD大鼠腹腔注射链脲佐菌素(60 mg/kg),检测空腹血糖>16.7 mmol/L后在足部造成一个0.3 mm×0.7 mm的创面,构建糖尿病足溃疡(Diabetic foot ulcer,DFU)模型。将DFU大鼠分为模型组、芹菜素高剂量组(80 mg/kg)、芹菜素低剂量组(40 mg/kg),另设空白组只作创面不构建糖尿病模型,每组10只。造模后24 h空白组与模型组灌胃生理盐水,芹菜素组分别灌胃高剂量与低剂量溶液,每天1次,持续14 d。在给药后第7、14天观察各组动物足创面愈合情况,记录愈合面积,计算愈合率;血糖仪检测各组动物给药后1、7、14 d的空腹血糖值;HE染色观察动物足创面愈合组织中损伤情况;RT-qPCR法检测动物足创面组织中白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)基因表达水平;Western blot法检测动物足创面组织中血管内皮生长因子(Vascular endothelial growth factor,VEGF)与转化生长因子-β_(1)(Transforming growth factor-β_(1),TGF-β_(1))蛋白表达情况。结果:与空白组相比,模型组动物14 d内空腹血糖值维持在高水平,未出现下降趋势,足部创面愈合速度慢,愈合率下降,创面组织中炎性细胞聚集程度严重,皮肤结构损伤严重,组织中IL-1β、IL-6和TNF-α基因表达升高,VEGF与TGF-β_(1)蛋白表达水平降低(P<0.05)。与模型组相比,芹菜素组动物14 d内空腹血糖值降低,足部创面面积减少,愈合率提高,降低组织中IL-1β、IL-6和TNF-α基因表达量与升高VEGF与TGF-β_(1)蛋白表达水平(P<0.05)。结论:芹菜素能通过减少炎症反应、促进血管与组织形成,帮助糖尿病足大鼠创面快速愈合。

Objective To explore whether apigenin can promote the wound healing of diabetic foot rats by reducing inflammation and promoting the formation of blood vessels and tissues.Methods SD rats were intraperitoneally injected with streptozotocin(60 mg/kg)to detect fasting blood glucose greater than 16.7 mmol/L,and a wound of 0.3 mm×0.7 mm was created in the foot to construct diabetic foot ulcer(DFU)model.DFU rats were divided into model group,apigenin high-dose group(80 mg/kg)and apigenin low-dose group(40 mg/kg),and control group was set as wound surface without diabetic model,with 10 rats in each group.24 h after modeling,the control group and the model group were given normal saline,and the apigenin group was given apigenin,once a day,for 14 days.On the 7th and 14th day after drug administration,the wound healing of each group was observed,the healing area was recorded,and the healing rate was calculated.Fasting blood glucose was measured at 1,7 and 14 d.HE staining was used to observe the injury of wound healing tissue.The expression levels of IL-1β,IL-6 and TNF-αin animal foot wounds were detected by RT-qPCR.Western blot was used to detect the expression of VEGF and TGF-β_(1) protein in animal foot wounds.Results Compared with control group,the fasting blood glucose value in the model group remained at a high level within 14 days without a downward trend,the healing speed of foot wounds was slow,the healing rate was decreased,the degree of inflammatory cell aggregation in the wound tissue was serious,the skin structure was seriously damaged,and the expression levels of IL-1β,IL-6 and TNF-αgenes in the tissue were significantly increased.The protein expression levels of VEGF and TGF-β_(1) were significantly decreased.Compared with model group,apigenin can reduce fasting blood glucose,promote foot wound healing,improve healing rate,repair skin structure,reduce the expression of IL-1β,IL-6 and TNF-αgenes,and increase the protein expression of VEGF and TGF-β_(1) in DFU rats within 14 days.Conclusion Apigenin can reduce inflammation,promote the formation of blood vessels and tissues,and promote rapid wound healing in diabetic foot rats.