局部应用胰岛素对糖尿病小鼠创面愈合的影响  

Effects of topical application of insulin on wound healing in diabetic mice

作　　者：李超飞[1] 刘琰[1] 陈雪莲[1] 章雄[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院灼伤整形科,200025

出　　处：《中华损伤与修复杂志（电子版）》2012年第1期42-46,共5页Chinese Journal of Injury Repair and Wound Healing(Electronic Edition)

基　　金：国家自然科学基金面上项目(81170761);上海市科委医学引导课题(10411965500)

摘　　要：探讨不同链脲佐菌素注射方法诱导的糖尿病模型的糖代谢特性,寻找具2型糖尿病特性的动物模型,并观察局部应用胰岛素对该模型小鼠全层皮肤缺损创面愈合速度和质量的影响,初步探索促愈机制。方法通过多次小剂量(多次小剂量组,n=10)和单次大剂量(单次大剂量组,n=10)链脲佐菌素腹腔注射诱导糖尿病小鼠模型,造模后4周检测糖代谢指标,比较两组动物的胰岛素抵抗特性。C57BL/6J小鼠(n=40)以多次小剂量链脲佐菌素腹腔注射的方法诱导糖尿病,胰腺组织学检查及连续血糖监测证实模型成功。造模后8周,在小鼠背部制造4个7mm直径的全层皮肤缺损创面,每日1次分别滴加20μl生理盐水(2个创面,对照组)、0.1U胰岛素/20μl生理盐水(1个创面,0.1U胰岛素处理组)和0.5U胰岛素/20μl生理盐水(1个创面,0.5U胰岛素处理组),直至创面完全愈合。观察创面上皮化过程,记录创面愈合时间,以ImageJ软件分析创面面积,计算创面愈合率。11d时创面取材,HE染色观察愈合创面皮肤组织结构,Masson染色观察创面胶原形态及分布,免疫组化方法观察并计算创面组织CD31阳性细胞的表达。结果与单次大剂量组相比,多次小剂量组链脲佐菌素腹腔注射诱导的糖尿病小鼠空腹血糖浓度、胰岛素水平和稳态模型胰岛素抵抗指数明显升高,胰岛素敏感指数显著降低,差异均有统计学意义(P﹤0.05)。0.5U、0.1U胰岛素处理组的糖尿病小鼠创面愈合时间分别为(10.6±1.5)d、(11.3±0.9)d,较对照组创面愈合时间(12±1.2)d缩短,组间差异均有统计学意义(P﹤0.05)。和对照组相比,0.5U、0.1U胰岛素处理组创面表皮钉突数量较多,胶原分布均匀致密,CD31阳性表达细胞数量增多,真皮及浅层皮下组织血管化良好。结论连续多次小剂量链脲佐菌素腹腔注射诱导的糖尿病模型具有2型糖尿病的胰岛素抵抗特性;局部应用胰岛素促进该糖尿病模型小�Objective To investigate the effects of topical application oI insulin on wounu nemmg in diabetic mice. Methods Diabetes mellitus was induced in C57BL/6J mice （n = 10, each group） by intraperitoneal injection of streptozotocin （STZ） using multiple injections with low dose or single injection with high dose manner. Four weeks after treatment, glucose metabolism index was assessed to compare the characteristics of insulin resistance between the two groups. C57BL/6J （n = 40）mice were induced to diabetic mellitus using multiple low doses of STZ intraperitoneal injections. Eight weeks after induction, 4 full-thickness skin wounds with diameter 7 mm were made on the back of diabetic mice. Each wound was treated with 20 μl NS ,0.1 unit insulin/20 μl NS ,0.5 unit insulin/20 μl NS and 20 μl NS respectively. Each group of wounds were used with mentioned drugs immediately after wounds making, once a day, until complete healing. At 0,1,3,5,7,9 and 11 days, transparent membranes were used to record wound areas and to calculate the healing rates. Meanwhile ,we observed the process of wound epithelialization and recorded the time of complete healing. At day 11, wound tissues were collected. H＆E staining and Masson staining were used to observe the structure of healed tissues. The angiogenesis of healed skin was qualified by CD31 immunohistochemistry. Results Compared to the single high dose injection group,the fasting blood glucose level, insulin level and homeostasis model assessment of insulin resistance were significantly increased in the multiple low doses injection group, while the insulin sensitivity index was markedly reduced （ P 〈 0.05 - 0.01 ）. The healing time in 0.1 and 0.5 unit insulin groups were （ 10.6 ±1.5 ） d and （ 11.3 ± 0.9） d, by contrast, the control group was （ 12 ± 1.2） d（P 〈 0.05）. The quality of wound healing in 0.1 and 0.5 unit insulin groups were significantly improved, which included the increased number of spikes in the epidermis, the normalization of coll

关 键 词：胰岛素 糖尿病 伤口愈合 血管 

分 类 号：R587.1[医药卫生—内分泌]