局部应用肉桂醛通过激活Nrf2通路促进糖尿病小鼠创口愈合

发布时间：2018-04-27 05:07

本文选题：肉桂醛 + 糖尿病溃疡　；参考：《第三军医大学学报》2017年19期

【摘要】：目的探讨局部应用肉桂醛(cinnamic aldehyde,CA)对糖尿病小鼠创口愈合的影响及其机制。方法 8周龄Nrf2野生型(Nrf2~(+/+))和Nrf2敲除型(Nrf2~(-/-))雄性SKH-1无毛小鼠各8只,持续5 d腹腔注射链脲霉素(streptozotocin,STZ,50 mg/kg),建立糖尿病小鼠模型。采用随机数字表法分为:(1)Nrf2~(+/+)鼠对照组(Nrf2~(+/+)Veh组);(2)Nrf2~(+/+)鼠CA治疗组(Nrf2~(+/+)CA组);(3)Nrf2~(-/-)鼠Veh组(Nrf2~(-/-)Veh组);(4)Nrf2~(-/-)鼠CA组(Nrf2~(-/-)CA组)(n=4)。STZ注射后第4周,在小鼠背部建立直径6 mm的全层皮肤切除创口。Nrf2~(+/+)CA组和Nrf2~(-/-)CA组术后当日开始局部应用20μL含4μmol/L CA的聚乙二醇400(polyethylene glycol400,PEG400),每隔1天干预直至第14天,收集创缘处皮肤,Nrf2~(+/+)Veh组和Nrf2~(-/-)Veh组采用20μL PEG400(Vehicle,Veh)局部应用作为空白对照。术后2周内每隔1天监测皮肤创口愈合面积评估愈合速率。免疫组化染色对比各组创缘处皮肤组织Nrf2蛋白、下游靶蛋白HO-1和氧化应激损伤相关指标8-oxo-d G的表达水平。结果局部应用CA明显加速Nrf2~(+/+)糖尿病小鼠创口愈合(P0.05),但是并不影响Nrf2~(-/-)糖尿病小鼠创口愈合(P0.05)。免疫组化示Nrf2~(+/+)糖尿病溃疡小鼠局部应用CA后,其创缘皮肤Nrf2的表达水平[(2.42±0.29)vs(7.42±0.73),P0.05]和下游靶蛋白HO-1的表达水平[(5.92±0.36)vs(8.88±0.53),P0.05]显著增强,8-oxo-d G的表达水平则明显减少[(9.46±0.28)vs(8.46±0.23),P0.05]。Nrf2~(-/-)糖尿病小鼠创口局部外用CA后,其创缘处皮肤Nrf2、HO-1及8-oxo-d G的表达水平与Nrf2~(-/-)Veh组相比并无明显变化。结论局部应用CA通过激活糖尿病小鼠皮肤组织Nrf2通路,减轻氧化应激损伤,从而促进糖尿病创口愈合。
[Abstract]:Objective to investigate the effect and mechanism of local application of cinnamic aldehydea (CA) on wound healing in diabetic mice. Methods eight weeks old male SKH-1 hairless mice of Nrf2 wild type and Nrf2 knockout type were injected intraperitoneally with streptozotocinia (STZ) 50 mg / kg for 5 days to establish diabetic model. A random digital table was used to divide the control group into two groups: the control group (/) and the control group (/ Veh group). The CA treatment group (/ CA group) was divided into two groups: the control group Nrf2Nrf2 (/) and the control group (/) the CA treated group Nrf2Nrf2 (/ CA group) and the control group (Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2Nrf2r-Nrf2Nrf2Nrf2Nrf2r-Nrf2r-r-1) (4 weeks after injection of the Veh group). To establish a full-thickness skin excision wound with a diameter of 6 mm on the back of the mice. (/ group A and group Nrf2~(-/-)CA) were given 20 渭 L polyethylene glycol 400(polyethylene glycol400 (PEG400) containing 4 渭 mol/L CA every 1 day until 14 days after operation. The local use of 20 渭 L PEG400Veh1 was used as a blank control. The wound healing area was monitored every 2 weeks after operation to evaluate the healing rate. Immunohistochemical staining was used to compare the expression levels of Nrf2 protein, downstream target protein HO-1 and oxidative stress related index 8-oxo-d G. Results the local application of CA accelerated the wound healing of Nrf2U (/) diabetic mice, but it did not affect the wound healing of Nrf2OU /-/ -DM mice. Immunohistochemical staining showed that Nrf2M (/) diabetic ulcer mice were treated with CA. The expression level of Nrf2 in the wound skin [2.42 卤0.29)vs(7.42 卤0.73] and the downstream target protein HO-1 (5.92 卤0.36)vs(8.88 卤0.53) significantly enhanced the expression level of 8-oxo-d G, but significantly decreased [9.46 卤0.28)vs(8.46 卤0.23 p0.05]. There was no significant change in the expression of Nrf2HO-1 and 8-oxo-d G in the skin of Nrf2~(-/-)Veh group. Conclusion Local application of CA can promote the healing of diabetic wound by activating the Nrf2 pathway of diabetic skin tissue and reducing oxidative stress injury.
【作者单位】：第三军医大学新桥医院内分泌科;
【基金】：国家自然科学基金面上项目(81471039);国家自然科学基金青年科学基金(81500647) 重庆市基础科学与前沿技术研究(CSTC2016jcyjA1584) 青年医生糖尿病研究项目(2015)~~
【分类号】：R587.2

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