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脑心通胶囊对Ⅱ型糖尿病小鼠伤口愈合的作用
宋敏1, 陈璐2, 李春晓1, 房志锐1, 张璐莎1, Joel Wake Coffie1, 张丽媛1, 马璐璐1, 王虹1
1.天津中医药大学中西医结合学院, 天津 301617;2.方剂学教育部重点实验室, 天津市中药药理学重点实验室, 天津中医药大学中医药研究院, 天津 301617
摘要:
[目的]研究脑心通胶囊(NaoXinTong,NXT)对Ⅱ型糖尿病小鼠伤口愈合的作用和作用机制。[方法]将8-12周db/+小鼠db/db小鼠适应性喂养1周后,按体质量随机分组db/+Saline组、db/db Saline、db/db NXT(0.7 g/kg)组,建立切除伤口夹板模型,每天灌胃给药并记录小鼠体质量,每两天监测空腹血糖并对伤口拍照测量伤口面积,分别在术后7、16 d取小鼠伤口处皮肤组织,小鼠伤口处皮肤组织进行切片或立即冷冻保存。HE染色观察伤口边缘肉芽组织的面积和上皮化,Lectin免疫荧光检测伤口周围毛细血管的密度,新鲜组织用来提取蛋白并用Western Blotting检测VEGF、PI3K/p-PI3K、AKT/p-AKT、eNOS/p-eNOS在伤口边缘的表达。[结果]与db/db Saline组相比,db/db NXT组小鼠伤口愈合率增加,肉芽组织面积和上皮化增加,伤口周围的血管密度和VEGF的表达增加,PI3K/AKT/eNOS的磷酸化增加,但在伤口愈合过程中糖尿病小鼠的体质量和空腹血糖没有变化。[结论]脑心通胶囊通过激活PI3K/AKT/eNOS信号通路增加VEGF表达促进血管新生,增加肉芽组织的形成和上皮化,加速Ⅱ型糖尿病小鼠伤口愈合。
关键词:  NXT  血管新生  伤口愈合  DFU  PI3K/AKT/eNOS信号通路
DOI:10.11656/j.issn.1673-9043.2019.04.21
分类号:R285.5
基金项目:天津市应用基础与前沿技术研究计划项目(16JCZDJC36300);国家国际科技合作专项基金资助项目(2015DFA30430);国家自然科学基金青年项目(81603329)。
Effect of Naoxintong capsule on wound healing in typeⅡ diabetic mice
SONG Min1, CHEN Lu2, LI Chunxiao1, FANG Zhirui1, ZHANG Lusha1, Joel Wake Coffie1, ZHANG Liyuan1, MA Lulu1, WANG Hong1
1.School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;2.Tianjin University of Traditional Chinese Medicine, Institute of Chinese Medicine, Tianjin Key Laboratory of Modern Chinese Medicine, Tianjin Key Laboratory of Traditional Chinese Medicine Pharmacology, Tianjin 301617, China
Abstract:
[Objective] To study the effect and mechanism of Naoxintong capsule (NXT) on wound healing in type 2 diabetic mice.[Methods] 8~12 weeks db/+ mice and db/db mice were randomly divided into db/+ Saline group, db/db Saline group and db/db NXT (0.7 g/kg). The splint model of excision wound was established. Oral administration and body weight was recorded every day. The fasting blood glucose was monitored and the wound area was measured by photography every two days. At days 7, 16 post-injury, the skin tissues were obtained and the skin tissues at the wounds of mice were sliced or cryopreserved immediately. HE staining and Lectin immunofluorescence was employed to evaluate granulation tissue formation, re-epithelialization and capillaries density around the wound, Western Blotting was used to measure the expression of VEGF, PI3K/P-PI3K, AKT/P-AKT and eNOS/P-eNOS at the edge of the wound.[Results] Compared with the db/db Saline group, the wound healing rate, granulation tissue formation and re-epithelialization, the expression of vascular density and vascular endothelial growth factor increased notably, and the phosphorylation of PI3K/AKT/eNOS increased in db/db NXT group, body weight and fasting blood glucose hadn't change in process of wound closure.[Conclusion] Naoxintong capsule can significantly accelerate wound healing and increase the granulation tissue formation, re-epithelialization and angiogenesis in type 2 diabetic mice by activating PI3K/AK/eNOS signaling pathway.
Key words:  NXT  angiogenesis  wound healing  DFU  PI3K/AKT/eNOS signaling pathway
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