小檗碱联合去铁胺对糖尿病大鼠创面愈合的影响  

Effect of berberine combined with deferoxamine on wound healing in diabetes rats

作　　者：刘丽娥 林健 何蓥蓥[2] 李锦惠 梁佳妹 吴志红 LIU Li-e(Gongchen Community Health Service Center,Licheng District,Putian 351100,Fujian,China)

机构地区：[1]莆田市荔城区拱辰社区卫生服务中心 [2]莆田学院药学与医学技术学院 [3]药物分析与检验医学福建省高校重点实验室(莆田学院) [4]福建东瑞制药有限公司,福建莆田351100

出　　处：《牡丹江医学院学报》2024年第6期21-26,共6页Journal of Mudanjiang Medical University

基　　金：莆田市科技局项目(2022SZ3001ptxy06);福建省大学生创新创业训练项目(S202211498018)。

摘　　要：目的 探讨小檗碱联合去铁胺对糖尿病大鼠皮肤伤口愈合的影响。方法 通过腹腔注射链脲佐菌素(streptozotocin,STZ)法建立大鼠2型糖尿病模型,并随机分成模型组、小檗碱组、去铁胺组、小檗碱联合去铁胺组;建立糖尿病大鼠背部创口模型,通过皮肤给药治疗7 d、14 d后对皮肤伤口拍照记录伤口形态变化,考察皮肤第7、14天伤口愈合率。通过HE染色观察第14天大鼠伤口组织的病理变化、Masson染色分析第14天的创口组织恢复情况和胶原变化,ELISA法测定血清中肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、白介素1β(interleukin1β,IL-1β)的含量,免疫组织化学染色法分析伤后第14天创口组织血小板-内皮细胞黏附分子(platelet endothelial cell adhesion molecule-1,CD31)和血管内皮生长因子(vascular endothelial growth factor,VEGF)的变化。结果 造模7 d、14 d后,小檗碱组、去铁胺组、小檗碱联合去铁胺组创面明显缩小,其中小檗碱联合去铁胺组创面愈合速度最快。HE和Masson染色显示,小檗碱组、去铁胺组、小檗碱联合去铁胺组创面可见胶原组织沉积,其中以联合给药组最多。免疫组化显示,与模型组比较,小檗碱组、去铁胺组、小檗碱联合去铁胺给药组CD31和VEGF表达明显增多(P<0.01),其中以小檗碱联合去铁胺组改善更明显。血清中TNF-α和IL-1β的含量,小檗碱组、小檗碱联合去铁胺组与模型组14 d时间点比较,差异有统计学意义(P<0.01或P<0.05),血清中TNF-α含量,去铁胺组与模型组比较,差异无统计学意义(P>0.05)。结论 小檗碱和去铁胺联合用药可以明显改善糖尿病大鼠创面愈合,其机制可能与炎症因子TNF-α、IL-1β和CD31、VEGF生长因子的含量变化有关。Objective To investigate the effect of berberine combined with deferoxamine on skin wound healing in diabetic rats.Methods Type 2 diabetes rat models were induced via intraperitoneal injection of streptozotocin(STZ),and the rats were randomly divided into a model group,a berberine group,a deferoxamine group and a combination group.A dorsal wound model was created in diabetic rats,and the rats were treated topically for 7 and 14 days.The morphological changes of the skin wound were recorded and the wound healing rate on the 7th and 14th day was investigated.The pathological changes of wound tissue on the 14th day were observed by HE staining,the wound tissue recovery and collagen changes were analyzed by Masson staining,the contents of tumor necrosis factor-α(TNF-α) and interleukin1 β(IL-1 β) in serum were determined by ELISA.The platelet-endothelial cell adhesion molecule(CD31) and vascular endothelial growth factor(VEGF) expression in wound tissue was analyzed by immunohistochemical staining.Results After 7 and 14 days of modeling,the wound was significantly reduced in berberine group,deferoxamine group and combination group,and the wound healing speed was the fastest in combination group.HE and Masson staining showed that collagen deposition in the wound tissues of all treatment groups,with the most prominent accumulation in the combination group.Compared with the model group,the expression of CD31 and VEGF in treatment groups increased significantly(P<0.01),especially in combination group.There was significant difference in the content of TNF-α and IL-1 β in serum between berberine group,combination group and model group at 14 days(P<0.01 or P<0.05),but there was no significant difference in serum TNF-α content between deferoxamine group and model group(P>0.05).Conclusion The combination of berberine and deferoxamine can significantly improve wound healing in diabetic rats,and its mechanism may be related to the regulation of inflammatory cytokines TNF-α,IL-1 β and growth factors CD31,VEGF.

关 键 词：小檗碱 去铁胺 糖尿病大鼠 创面愈合 

分 类 号：R587.1[医药卫生—内分泌]