EFFECTS OF NERVE GROWTH FACTOR-INSULIN COMPOSITE GEL ON DEEP SECOND DEGREE SCALD WOUND HEALING IN DIABETIC RATS_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WANG Min ¹ , XUE Xiaodong ¹ , XIE Peilin ² , ZHANG Jibei ³

1Department of Plastic Surgery, 2Department of Burn Surgery, People’s Hospital of Gansu Province, the First Clinical College of Lanzhou University, Lanzhou Gansu, 730000, P.R.China;;
3Department of Burn and Plastic Surgery, Central Hospital of Cangzhou City. Corresponding author: XUE Xiaodong, E-mail: xiaodongxue@hotmail.com;

Corresponding author：

Keywords：

Insulin; Nerve growth factor; Composite gel Burn wound healing; Diabetic rat

DOI：

10.7507/1002-1892.20130041

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Objective To prepare nerve growth factor (NGF)-insulin composite gel and observe the effects of NGF-insulin composite gel on deep second degree scald wound healing in diabetic rats. Methods Carbomer 980, NGF (4 000 U), and insulin (800 U) were used to prepare the insulin gel, NGF gel, and NGF-insulin composite gel. The character of NGF-insulin composite gel was observed, and the in vitro drug release was tested. Seventy-five SPF Wistar male rats, weighing 200-250 g, were divided into 5 groups randomly, 15 rats each group: normal control group (group A), diabetes control group (group B), insulin gel treatment group (group C), NGF gel treatment group (group D), and NGF-insulin composite gel treatment group (group E). The type 1 diabetes rat model was established by intraperitoneal injection of Streptozotocin (55 mg/kg) in groups B, C, D, and E, while the rats in group A were injected with the same dose of citric acid and calcium citrate buffer. After modeling success, deep second degree scald wound on the back was made with constant temperature water bath box. Wounds were treated with carbomer blank gel in groups A and B, with insulin composite gel in group C, with NGF gel in group D, and with NGF-insulin composite gel in group E, once a day. At 3, 7, 11, 15, and 21 days after injury, the scald wound healing was observed and healing rate was calculated; the full-thickness skin specimens were harvested from 3 rats of each group for histological and immuohistochemical staining observation. Results The NGF-insulin composite gel was clear and transparent, and had good moisture retention capacity and adhesion; it was easy to apply and clean up. The drug release in vitro lasted more than 24 hours and maintained for 30 days. No rat died during the experiment. At 3 days after injury, wound area did not reduce in all groups; at 7, 11, 15, and 21 days, group E had the highest wound healing rate, and group B had the lowest; significant differences were found between group E and group B and when compared with the other groups (P lt; 0.05). HE staining showed that group E surpassed other groups in the growth of granulation tissue and collagen fiber. Immunohistochemical results showed that the CD34 and proliferating cell nuclear antigen (PCNA) expressed at 3 days, and the number of positive cells increased gradually with time; the microvessel density and PCNA expression were highest in group E and were lowest in group B, showing significant differences when compared with the other groups and between group E and group B (P lt; 0.05). Conclusion NGF-insulin composite gel can improve deep second degree scald wound healing in diabetic rats.

Citation： WANG Min,XUE Xiaodong,XIE Peilin,ZHANG Jibei. EFFECTS OF NERVE GROWTH FACTOR-INSULIN COMPOSITE GEL ON DEEP SECOND DEGREE SCALD WOUND HEALING IN DIABETIC RATS. Chinese Journal of Reparative and Reconstructive Surgery, 2013, 27(2): 182-188. doi: 10.7507/1002-1892.20130041 Copy

1.	15 Turrini P, Gaetano C, Antonelli A, et al. Nerve growth factor induces angiogenic activity in a mouse model of hindlimb ischemia. Neurosci Lett, 2002, 323(2): 109-112. 16 Calza L, Giardino L, Giuliani A, et al. Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors. Proc Natl Acad Sci U S A, 2001, 98(7): 4160-4165.
2.
3.
4.	乔亮. 转化医学与糖尿病难愈创面研究相关探讨. 中华烧伤杂志, 2010, 26(6): 472-473.
5.	常飞, 薛晓东, 谢沛霖, 等. 联合应用NGF和胰岛素对糖尿病大鼠烫伤创面表皮干细胞的影响. 现代生物医学进展, 2012, 12(7): 1236-1240.
6.	张冀北, 薛晓东, 谢沛霖, 等. 局部联合应用NGF及胰岛素对糖尿病大鼠烫伤创面血管形成及Bcl-2、Bax表达的影响. 中国修复重建外科杂志, 2011, 25(3): 354-360.
7.	谢沛霖, 薛晓东, 张冀北, 等. 局部应用神经生长因子联合胰岛素对糖尿病大鼠烫伤创面愈合及HIF-1α和VEGF表达的影响. 中国医师杂志, 2011, 13(1): 33-37.
8.	Agarwal V, Singh SK, Reddy IK, et al. Cataplasm-based controlled drug delivery: development and optimization of a novel formulation. Drug Dev Ind Pharm, 1999, 25(5): 659-665.
9.	周冼苡, 周雪雪, 曾抗, 等. 复方胰岛素凝胶的研制及含量测定. 中国药房, 2006, 17(19): 1474-1475.
10.	农慧, 盛庆寿, 梁健, 等. STZ诱导糖尿病大鼠模型的研究. 广西医科大学学报, 2010, 27(1): 69-72.
11.	孙同柱, 付小兵, 顾小曼, 等. 重组人表皮生长因子促进兔烫伤创面愈合的实验研究. 实验动物科学与管理, 2000, 17(4): 12-14.
12.	杨洪存, 曲悦, 冯秀萍. 重组碱性成纤维细胞生长因子凝胶剂的制备. 中国生物制品学杂志, 2009, 22(10): 1002-1004.
13.	李书国, 曾秋棠. 胰岛素对牛胸主动脉内皮细胞血管内皮生长因子表达的影响及其与一氧化氮合酶的关系. 临床心血管病杂志, 2005, 21(8): 476-478.
14.	陆建芝. 胰岛素创面换药治疗糖尿病溃疡. 浙江创伤外科, 2001, 6(3): 146.
15.	柳晖, 陈武鹏, 向红霞, 等. 胰岛素与重组人表皮生长因子局部联合应用对大鼠深Ⅱ度烫伤创面愈合的影响. 实用医学杂志, 2009, 25(3): 359-361.
16.	Foster PA, Wicks S, Foster M, et al. Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events. J Pathol, 2002, 197(2): 245-255.
17.	Cantarella G, Lempereur L, Presta M, et al. Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo. FASEB J, 2002, 16(10): 1307-1309.
18.	耿纪录, 陆菊明. 内皮细胞功能紊乱与糖尿病大血管病变. 天津医药, 1999, 27(8): 510-512.
19.	林炜栋, 陆树良, 青春, 等. 晚期糖基化终产物修饰人血清白蛋白对人血管内皮细胞的生长抑制作用. 中华医学杂志, 2003, 83(7): 572-576.
20.	施君, 张文川. 糖尿病周围神经病变发病机制的研究进展. 上海交通大学学报: 医学版, 2012, 32(1): 116-119.
21.	庞宗然, 苏晓慧, 刘祖涵, 等. 微循环障碍与糖尿病及其并发症关系. 时珍国医国药, 2011, 22(4): 988-989.

1. 15 Turrini P, Gaetano C, Antonelli A, et al. Nerve growth factor induces angiogenic activity in a mouse model of hindlimb ischemia. Neurosci Lett, 2002, 323(2): 109-112. 16 Calza L, Giardino L, Giuliani A, et al. Nerve growth factor control of neuronal expression of angiogenetic and vasoactive factors. Proc Natl Acad Sci U S A, 2001, 98(7): 4160-4165.
2.
3.
4. 乔亮. 转化医学与糖尿病难愈创面研究相关探讨. 中华烧伤杂志, 2010, 26(6): 472-473.
5. 常飞, 薛晓东, 谢沛霖, 等. 联合应用NGF和胰岛素对糖尿病大鼠烫伤创面表皮干细胞的影响. 现代生物医学进展, 2012, 12(7): 1236-1240.
6. 张冀北, 薛晓东, 谢沛霖, 等. 局部联合应用NGF及胰岛素对糖尿病大鼠烫伤创面血管形成及Bcl-2、Bax表达的影响. 中国修复重建外科杂志, 2011, 25(3): 354-360.
7. 谢沛霖, 薛晓东, 张冀北, 等. 局部应用神经生长因子联合胰岛素对糖尿病大鼠烫伤创面愈合及HIF-1α和VEGF表达的影响. 中国医师杂志, 2011, 13(1): 33-37.
8. Agarwal V, Singh SK, Reddy IK, et al. Cataplasm-based controlled drug delivery: development and optimization of a novel formulation. Drug Dev Ind Pharm, 1999, 25(5): 659-665.
9. 周冼苡, 周雪雪, 曾抗, 等. 复方胰岛素凝胶的研制及含量测定. 中国药房, 2006, 17(19): 1474-1475.
10. 农慧, 盛庆寿, 梁健, 等. STZ诱导糖尿病大鼠模型的研究. 广西医科大学学报, 2010, 27(1): 69-72.
11. 孙同柱, 付小兵, 顾小曼, 等. 重组人表皮生长因子促进兔烫伤创面愈合的实验研究. 实验动物科学与管理, 2000, 17(4): 12-14.
12. 杨洪存, 曲悦, 冯秀萍. 重组碱性成纤维细胞生长因子凝胶剂的制备. 中国生物制品学杂志, 2009, 22(10): 1002-1004.
13. 李书国, 曾秋棠. 胰岛素对牛胸主动脉内皮细胞血管内皮生长因子表达的影响及其与一氧化氮合酶的关系. 临床心血管病杂志, 2005, 21(8): 476-478.
14. 陆建芝. 胰岛素创面换药治疗糖尿病溃疡. 浙江创伤外科, 2001, 6(3): 146.
15. 柳晖, 陈武鹏, 向红霞, 等. 胰岛素与重组人表皮生长因子局部联合应用对大鼠深Ⅱ度烫伤创面愈合的影响. 实用医学杂志, 2009, 25(3): 359-361.
16. Foster PA, Wicks S, Foster M, et al. Cellular pathology changes in rat skin following intradermal injection of nerve growth factor: neutrophil-dependent and -independent events. J Pathol, 2002, 197(2): 245-255.
17. Cantarella G, Lempereur L, Presta M, et al. Nerve growth factor-endothelial cell interaction leads to angiogenesis in vitro and in vivo. FASEB J, 2002, 16(10): 1307-1309.
18. 耿纪录, 陆菊明. 内皮细胞功能紊乱与糖尿病大血管病变. 天津医药, 1999, 27(8): 510-512.
19. 林炜栋, 陆树良, 青春, 等. 晚期糖基化终产物修饰人血清白蛋白对人血管内皮细胞的生长抑制作用. 中华医学杂志, 2003, 83(7): 572-576.
20. 施君, 张文川. 糖尿病周围神经病变发病机制的研究进展. 上海交通大学学报: 医学版, 2012, 32(1): 116-119.
21. 庞宗然, 苏晓慧, 刘祖涵, 等. 微循环障碍与糖尿病及其并发症关系. 时珍国医国药, 2011, 22(4): 988-989.

Chinese Journal of Reparative and Reconstructive Surgery

EFFECTS OF NERVE GROWTH FACTOR-INSULIN COMPOSITE GEL ON DEEP SECOND DEGREE SCALD WOUND HEALING IN DIABETIC RATS

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