腺苷酸活化蛋白激酶α在高血糖大鼠急性创面再上皮化过程中的表达  

Expression of AMP Activated Protein Kinase α in the Process of Acute Wound Re-epithelialization in Hyperglycemic Rats

作　　者：王治兵 徐秋燕 王宝宏 张艳冰 曹露莹 马凯 侯绍章 董俭达 WANG Zhibing;XU Qiuyan;WANG Baohong;ZHANG Yanbing;CAO Luying;MA Kai;HOU Shaozhang;DONG Jianda(Ningxia Helan County People’s Hospital,Helan 750200,China;Clinical College of Ningxia Medical University,Yinchuan 750004,China;Department of Pathology,Basic Medical College of Ningxia Medical University,Yinchuan 750004,China)

机构地区：[1]宁夏贺兰县人民医院,贺兰750200 [2]宁夏医科大学临床学院,银川750004 [3]宁夏医科大学基础医学院病理学系,银川750004

出　　处：《宁夏医科大学学报》2021年第3期217-223,230,共8页Journal of Ningxia Medical University

基　　金：国家自然科学基金(82060155);宁夏自然科学基金(NZ15084,NZ17053);中国科学院“西部之光”人才培养引进计划;宁夏糖尿病及其并发症基础和临床研究创新团队项目(NXKJT2019010);国家级大学生创新创业训练计划备案项目(201810752006)。

摘　　要：目的探讨腺苷酸活化蛋白激酶α(AMPKα)在糖尿病急性创面愈合中的作用。方法30只成年雄性SD大鼠随机分为正常血糖对照组(NC)、高血糖组(DC)及高血糖二甲双胍干预组(DM)。利用链脲佐菌素(STZ)腹腔注射制备高血糖大鼠模型,在大鼠背部制备直径5 mm全层皮肤创面,DM组大鼠创面二甲双胍霜剂局部处理。于实验第3、6、9和12天观察并记录创面愈合情况,并收集创面组织,石蜡切片,行HE染色及AMPKα的免疫组化染色,利用Image J软件对AMPKα染色强度进行半定量检测。结果DC组及DM组大鼠血糖均高于16.7 mmol·L^(-1)。与NC组大鼠比较,DC组和DM组大鼠尾静脉血糖升高(P<0.05);与NC组大鼠比较,DC组和DM组大鼠体质量降低(P<0.05)。伴随实验时间变化,各组大鼠伤口均呈减小趋势,实验第12天DC组大鼠出现伤口延迟愈合(delayed wound healing,DWH)。实验第12天,DC组RE过程尚未完成,DC组镜下表皮伤口长度大于NC组及DM组(P<0.05);NC组及DM组表皮伤口愈合已完成。AMPKα在正常表皮基底细胞中低表达,棘细胞层及角化细胞层中高表达,DC组表达高于NC组(P>0.05)。实验第6天和第12天,与对应周边正常表皮区比较,NC组、DC组和DM组大鼠创面RE区AMPKα均出现表达降低(P均<0.05)。实验第6天和第12天,创面RE区AMPKα相对表达水平的组间比较显示,DM组最低(P均<0.05)。结论高血糖大鼠急性创面伤口延迟愈合,二甲双胍对高血糖大鼠创面愈合具有促进作用,可能与再上皮化区AMPKα下调有关。Objective To investigate the expression and significance of AMP activated protein kinaseα(AMPKα)in the re-epithelialization(RE)epidermis of keratinocytes(KCS)in hyperglycemia rats.Methods Thirty adult male SD rats were randomly divided into normal glucose control group(NC),hyperglycemia group(DC)and hyperglycemic metformin intervention group(DM).Streptozotocin(STZ)was injected intraperitoneally to establish hyperglycemic rat model.Full thickness skin wounds with a diameter of 5 mm were prepared on the back of rats.The wounds in DM group were treated with metformin cream.The wound healing was observed and recorded on the 3rd,6th,9th and 12th day of the experiment.The wound tissues and paraffin sections were collected for HE staining and immunohistochemical staining of AMPKα.The staining intensity of AMPKαwas semi-quantitatively detected by ImageJ software.Results The blood glucose of DC and DM rats were higher than 16.7 mmol·L^(-1).Compared with NC group,the tail vein blood glucose of DC and DM group increased(P<0.05);compared with NC group,the weight of DC and DM groups decreased(P<0.05).With the change of experimental time,the wound of each group showed a decreasing trend.On the 12th day,delayed wound healing(DWH)appeared in DC group.On the 12th day of the experiment,the RE process in DC group was not completed,the wound length of DC group was significantly larger than that of NC and DM group(P<0.05);the wound healing of NC and DM group was completed.The expression of AMPKαin the basal cells of normal epidermis was low,and the expression of AMPKαwas high in the stratum spinosum and stratum corneum.The expression of AMPKαin DC group was higher than that in NC group(P>0.05).On the 6th and 12th day of the experiments,compared with the corresponding peripheral normal epidermal area,the expression of AMPKαin RE area of NC,DC and DM groups decreased significantly(P<0.05).On the 6th and 12th day of the experiment,the relative expression of AMPKαin RE area of wound surface in DM group was the lowest,and the di

关 键 词：高血糖 创面愈合 再上皮化 腺苷酸活化蛋白激酶 二甲双胍 

分 类 号：R587.1[医药卫生—内分泌] R826.5[医药卫生—内科学]