槲皮素对糖尿病伤口的促愈合作用及相关机制研究

Effect of quercetin on healing of diabetic wound healing and its related mechanisms

目的探讨槲皮素对糖尿病伤口的促愈合作用及潜在机制。方法通过腹腔注射链脲佐菌素诱导构建SD大鼠糖尿病模型,成模8周后行全层皮肤切除术构建糖尿病大鼠伤口模型,将大鼠随机分为模型组(Model组)、溶剂对照组(10%DMSO组)和槲皮素组(Quer组),并于伤口造模当天开始局部给药,连续10 d;于伤口给药第0、3、7、10天拍照记录伤口图像并计算伤口愈合率,采集给药第7天的伤口组织进行HE染色、Masson染色、免疫组化标记(M2型巨噬细胞特异性标记CD206和M1型巨噬细胞特异性标记i NOS),经RT-qPCR检测i NOS、Msr-1、Arg-1、IL-6、TNF-α、IL-10在mRNA水平的表达水平。结果伤口给药第10天,槲皮素组的伤口愈合率大于模型组和溶剂对照组(P<0.05);槲皮素组的伤口组织中炎症细胞数量明显减少,胶原蛋白着色强度、成纤维细胞分布程度和血管生成率评分、CD206阳性细胞数均明显高于模型组和溶剂对照组(P<0.05);槲皮素组i NOS阳性细胞数明显低于模型组和溶剂对照组(P <0. 05);槲皮素组Msr-1和Arg-1、IL-10的表达水平均明显高于模型组和溶剂对照组(P<0.05);槲皮素组i NOS、IL-6、TNF-α的表达水平均明显低于模型组和溶剂对照组(P <0. 05)。结论槲皮素促进糖尿病大鼠伤口愈合,其机制可能与槲皮素促使巨噬细胞向M2型极化,抑制巨噬细胞向M1型极化,减轻糖尿病伤口部位炎症反应有关。

Objective To investigate the effect of quercetin on diabetic wound healing and its potential mechanism.Methods SD rat diabetic model was established by intraperitoneal injection of streptozotocin.Full-thickness skin resection was performed 8 weeks after the model was established.The rats were randomly divided into the model group,solvent control group(10%DMSO group)and quercetin group(Quer group).Local administration was started on the day of wound modeling for 10 consecutive days.Images of wounds were taken and wound healing rates were calculated on day 0,3,7 and 10 after administration.The wound tissues on day 7 were collected for HE staining,Masson staining and immunohistochemical markers(M2 macrophage specific markers CD206 and M1 macrophage specific markers i NOS).The expression levels of IL-6,TNF-αIL-10,Msr-1,Arg-1 and i NOS were detected by RT-qPCR.Results The wound healing rate of quercetin group was higher than that of the model group and solvent control group on the 10 th day of wound administration(P<0.05).Collagen staining intensity,fibroblast distribution and angiogenesis score,CD206 positive cells in wound tissue of quercetin group were significantly higher than those of the model group and solvent control group(P<0.05).The number of i NOS positive cells in quercetin group was significantly lower than that in the model group and solvent control group(P<0.05).Meantime,the expressions of Msr-1,Arg-1 and IL-10 were significantly increased,but the levels of i NOS,IL-6 and TNF-αwere decreased in quercetin group(P<0.05).Conclusion Quercetin can promote the healing of refractory wounds in diabetic rats.The mechanism may be related to quercetin promoting M2 macrophage polarization,inhibiting M1 macrophage polarization,and alleviating inflammation in diabetic wound.