黄芪甲苷促糖尿病皮肤溃疡大鼠骨髓内皮祖细胞动员的机制  

Mechanism of astragaloside IV promoting bone marrow EPCs mobilization in diabetic ulcer rats

作　　者：张璐瑶 蔡诗敏 张熙[2] 宋小琴 邹晓玲 肖郁婷 杨莹 危洋 黄鸿宇 熊武 Zhang Luyao;Cai Shimin;Zhang Xi;Song Xiaoqin;Zou Xiaoling;Xiao Yuting;Yang Ying;Wei Yang;Huang Hongyu;Xiong Wu(College of Integrative Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,China;Department of Burn Plastic Surgery,The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Department of Scientific Research,Brain Hospital of Hunan Province,Changsha 410007,China)

机构地区：[1]湖南中医药大学中西医结合学院,长沙410208 [2]湖南中医药大学第一附属医院烧伤整形外科,长沙410007 [3]湖南省脑科医院(湖南中医药大学临床医学院)科研部,长沙410007

出　　处：《中国医师杂志》2024年第3期376-381,386,共7页Journal of Chinese Physician

基　　金：湖南中医药大学一流学科研究生开放基金项目(2020ZXYJH77);湖南省卫生健康委科研计划项目(202203064523)。

摘　　要：目的探讨黄芪甲苷(AS-IV)调控基质细胞衍生因子-1α(SDF-1α)/CXC趋化因子受体4(CXCR4)信号轴对糖尿病皮肤溃疡(DSU)大鼠骨髓内皮祖细胞(EPCs)动员至外周血的影响。方法选取24只SPF级SD雄性大鼠腹腔注射30 mg/kg 1%(质体比)链脲佐菌素,制成2型糖尿病大鼠模型,再于腰背部两侧各剪取直径为2 cm的圆形全层皮肤,制成糖尿病大鼠皮肤溃疡模型,后随机分为AS-IV组(50 mg/kg AS-IV)、阻滞剂组(50 mg/kg AS-IV+5 mg/kg AMD3100)和模型组,同时设置空白组(n=8),采用腹腔注射给药,模型组和空白组用等体积0.9%的NaCl处理,采集第10天大鼠外周血、股骨骨髓和创面新生组织,流式细胞术检测各组大鼠外周血EPCs数量,酶联免疫吸附法(ELISA)检测大鼠外周血、股骨骨髓和创面新生组织SDF-1α和CXCR4的蛋白表达情况;同时检测各组创面愈合率。结果造模后第10、21天各组大鼠创面愈合率比较,空白组愈合最快,模型组愈合最慢,AS-IV组愈合情况优于模型组和阻滞剂组,差异有统计学意义(均P<0.05)。造模后第10天空白组、AS-IV组、阻滞剂组外周血EPCs阳性率均显著高于模型组(均P<0.05),阻滞剂组外周血EPCs阳性率均显著低于AS-IV组(P<0.05)。造模后第10天模型组创面、血清、骨髓SDF-1α和CXCR4的蛋白表达均为最少,空白组的蛋白表达最高(均P<0.05),AS-IV组创面、血清、骨髓SDF-1α和CXCR4的蛋白表达显著高于阻滞剂组和模型组,差异有统计学意义(均P<0.05)。结论黄芪甲苷通过调控SDF-1α/CXCR4信号轴,促进糖尿病溃疡大鼠内皮祖细胞从骨髓动员和迁移至外周血,可作为种子细胞参与糖尿病溃疡创面血管新生,以促进糖尿病皮肤溃疡愈合。Objective To investigate the effect of astragaloside IV(AS-IV)regulating the signal axis of stromal cell-derived factor-1α(SDF-1α)/CXC chemokine receptor 4(CXCR4)on the mobilization of bone marrow endothelial progenitor cells(EPCs)to peripheral blood in diabetes skin ulcer(DSU)rats.Methods Twenty four SPF grade male Sprague Dawley(SD)rats were selected to make the model of type 2 diabetes rats by intraperitoneal injection of 30 mg/kg 1%(plastid ratio)streptozotocin,and then round full-thickness skin with a diameter of 2 cm was cut on both sides of the waist and back to make the skin ulcer model of diabetes rats.After that,they were randomly divided into AS-IV group(50 mg/kg AS-IV),blocker group(50 mg/kg AS-IV+5 mg/kg AMD3100)and model group.At the same time,a blank group(n=8)was set up,The drug was administered via intraperitoneal injection,and the model group and blank group were treated with 0.9%NaCl of equal volume.On the 10th day,peripheral blood,femoral bone marrow,and wound neovascularization tissues of rats were collected.The number of EPCs in peripheral blood of each group of rats was measured by flow cytometry,and the protein expression of SDF-1αand CXCR4 in peripheral blood,femoral bone marrow,and wound neovascularization tissues of rats was detected by enzyme-linked immunosorbent assay(ELISA);At the same time,the wound healing rates of each group were tested.Results On the 10th and 21st day after modeling,the wound healing rate of each group of rats was compared.The blank group healed the fastest,while the model group healed the slowest.The AS-IV group had better healing than the model group and the blocker group,and the difference was statistically significant(all P<0.05).On the 10th day after modeling,the positive rates of peripheral blood EPCs in the white group,AS-IV group,and blocker group were significantly higher than those in the model group(all P<0.05),while the positive rates of peripheral blood EPCs in the blocker group were significantly lower than those in the AS-IV group(all P<0.05).On

关 键 词：黄芪甲苷 皮肤溃疡 糖尿病并发症 内皮祖细胞 基质细胞衍生因子1Α 受体 CXCR4 

分 类 号：R285.5[医药卫生—中药学]