局部应用胰岛素对糖尿病大鼠烫伤创面愈合的影响

目的研究局部应用胰岛素对糖尿病大鼠烫伤创面愈合的作用,初步探索相关机制。方法 60只Wistar大鼠经高脂饮食喂养和小剂量脲佐菌素（STZ）多次注射诱导糖尿病,5周后,造成背部皮肤20%TBSA深Ⅱ度烫伤。随机分为胰岛素治疗组和对照组（每组30只大鼠）,分别于创面下浸润注射0.2 U中性胰岛素和等体积0.9%氯化钠溶液。观察创面愈合速度及伤后第1、4和12天两组创面表皮角质形成细胞迁移、炎症细胞浸润以及胶原沉积情况。酶联免疫吸附测定法检测创面活化素A（Activin A）、单核细胞趋化蛋白-1（MCP-1）和血小板衍生因子A（PDGF-A）水平。结果胰岛素治疗组创面愈合时间明显缩短,血糖无明显变化。和对照组相比,胰岛素治疗组伤后第4天创面表皮迁移舌长度明显延长;伤后第12天创面胶原沉积增加;创面巨噬细胞浸润和消退的时间提前,巨噬细胞在创面表达特征与创面MCP-1表达趋势一致。伤后第1、4天胰岛素治疗组创面Activin A的表达分别（142.52±15.26）pg/mL和（271.46±49.73）pg/mL,较对照组创面的（52.36±33.18）pg/mL和（46.08±8.92）pg/mL明显增加（P=0.0057,0.0001）,PDGF-A于伤后第1、4天的表达分别为（52.12±9.00）pg/mL和（74.75±7.00）pg/mL较对照组的（47.35±8.21）pg/mL和（34.07±5.05）pg/mL也有明显增加（P=0.4080,0.0001）。结论局部应用胰岛素促进创面巨噬细胞的浸润和提早消退、促进表皮细胞的迁移和血管生成相关细胞因子表达和胶原组织沉积,从而促进糖尿病大鼠烫伤创面的愈合。

Effects of insulin on diabetic scald rat wound healing

Objective To investigate the effect of topical application of insulin on diabetic burn wound healing of rats and underline mechanism. Methods Sixty rats were induced to be diabetic by multiple intraperitoneal injections with a low dose of STZ after 8 weeks of high-fat diet feeding. After 5 weeks of induction,deep partial thickness burn were inflicted to the back of the rats and make burn size to 20%total body surface area and the rats were randomLy divided into topical application of insulin and saline control group（ n = 30）. In the 1th,4th and 12 th days after scalding,samples were collected for histological analysis and protein was extracted for the analysis of Activin A, MCP-1and PDGF-A by ELISA.Results The topical application of 0. 2U insulin significantly accelerates the wound healing of diabetic scalded rats without any significant effect on glucose level. The migration tongue were longer than the control saline group measured in 4 days after scalding and the healing time of the topical insulin application group in shorter than the control group. The extracellular matrix deposition impairment in diabetic rat was significantly rescued by the topical application of insulin when observed in the 12 days after wounding. The infiltration and resolution time of the inflammation cells were in advanced and in line with this phenomenon was the expression of MCP-1 in the first day＇s wound bed. In the insulin application group,the expression of Activin A in the first and fourth days were（ 142. 52 ± 15. 26） pg /mLand（ 271. 46 ± 49. 73） pg /mL which were significant higher when compared with the saline application group（ 52. 36 ± 33. 18） pg /mL and（ 46. 08 ±8. 92） pg /mL separately（ P = 0. 0057,0. 0001）. The PDGF-A level in the insulin application group were（ 52.12 ± 9.00） pg/mL and（ 74. 75 ± 7. 00） pg/mL which were also significant higher than the saline application group（ 47. 35 ± 8. 21） pg /mL and（ 34. 07 ± 5. 05） pg /mL separately（ P = 0. 4080,0. 0001）.Conclusion