重组人神经生长因子对糖尿病大鼠难愈创面愈合的影响
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摘要
目的研究重组人神经生长因子(recombinant human nerve growth factor,rh NGF)对糖尿病大鼠合并难愈创面的治疗效果。方法腹腔注射链脲佐菌素(60 mg·kg~(-1))诱导大鼠糖尿病模型,并在大鼠背部造成一圆形烫伤创面,建立糖尿病合并难愈创面的动物模型。用药组rh NGF(3、6、12μg·kg~(-1))肌肉注射给药,每天1次,连续21 d。测定大鼠伤口面积,HE染色和透射电镜检查创面皮肤组织病理形态学变化。结果 rh NGF明显减小糖尿病大鼠烫伤创伤面积(P <0. 05); HE染色结果表明,rh NGF明显促进糖尿病大鼠烫伤创面纤维细胞和毛细血管再生;透射电镜结果表明,rh NGF对糖尿病大鼠烫伤创面皮肤的上皮细胞结构排列、细胞连接以及上皮下胶原等超微结构有明显改善作用。结论rh NGF对糖尿病大鼠烫伤性难愈创面具有促进愈合的作用。
Aim To investigate the effect of recombinant human nerve growth factor( rhNGF) on refractory wound model in diabetic rats. Methods Male SD rats were injected intraperitoneally with streptozotocin( 60 mg·kg~(-1)) to prepare a diabetes model; scald wound was prepared on the back of rats to establish a model of refractory wound in diabetic rats. The rats were treated with rh NGF( 3,6,12 μg·kg~(-1),i. m.) once for 21 days. The therapeutic effect of rhNGF on scald refractory wound in diabetic rats was detected by measurement of the wound area,HE staining and transmission electron microscopy examine. Results The wound healing rate of diabetic rats was slower than that of normal control group( P < 0. 01),and rhNGF significantly reduced the scald wound area of diabetic rats( P <0. 05); rhNGF could promote the regeneration of fibroblasts and capillaries in the wound; rhNGF significantly improved the arrangement of epithelial cells,cell connection and subepithelial collagen structure in diabetic rats. Conclusion rhNGF could promote the recovery of refractory scald wound in diabetic rats.
Aim To investigate the effect of recombinant human nerve growth factor( rhNGF) on refractory wound model in diabetic rats. Methods Male SD rats were injected intraperitoneally with streptozotocin( 60 mg·kg~(-1)) to prepare a diabetes model; scald wound was prepared on the back of rats to establish a model of refractory wound in diabetic rats. The rats were treated with rh NGF( 3,6,12 μg·kg~(-1),i. m.) once for 21 days. The therapeutic effect of rhNGF on scald refractory wound in diabetic rats was detected by measurement of the wound area,HE staining and transmission electron microscopy examine. Results The wound healing rate of diabetic rats was slower than that of normal control group( P < 0. 01),and rhNGF significantly reduced the scald wound area of diabetic rats( P <0. 05); rhNGF could promote the regeneration of fibroblasts and capillaries in the wound; rhNGF significantly improved the arrangement of epithelial cells,cell connection and subepithelial collagen structure in diabetic rats. Conclusion rhNGF could promote the recovery of refractory scald wound in diabetic rats.
引文
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[10]秦迪,张慧杰,杨希营,等.抗氧化肽AOP1对小鼠皮肤烫伤创面愈合修复的影响[J].中国药理学通报,2018,34(2):225-31.[10]Qin D,Zhang H J,Yang X Y,et al.Effect of antioxidant peptide AOP1 on healing repair of skin burns in mice[J].Chin Pharmacol Bull,2018,34(2):225-31.
[11]Goyal S N,Reddy N M,Patil K R,et al.Challenges and issues with streptozotocin-induced diabetes-A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics[J].Chem-Biol Interact,2016,244:49-63.
[12]Ji Y,Zhang A,Chen X,et al.Sodium humate accelerates cutaneous wound healing by activating TGF-beta/Smads signaling pathway in rats[J].Acta Pharm Sin B,2016,6(2):132-40.
[13]Kruse C R,Singh M,Sorensen J A,et al.The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats[J].J Surg Res,2016,206(2):418-26.
[14]Nakamichi M,Akishima-Fukasawa Y,Fujisawa C,et al.Basic fibroblast growth factor induces angiogenic properties of fibrocytes to stimulate vascular formation during wound healing[J].Am JPathol,2016,186(12):3203-16.
[15]Langoni Cassettari L,Colli Rocha Dias P,Natalia Lucchesi A,et al.Continuous electrical current and zinc sulphate administered by transdermal iontophoresis improves skin healing in diabetic rats induced by alloxan:morphological and ultrastructural analysis[J].JDiabetes Res,2014,2014:980232.
[2]Seo D K,Lee H S,Park J,et al.Diabetic foot complications despite successful pancreas transplantation[J].Foot Ankle Int,2017,38(6):656-61.
[3]杨选鑫,惠琦,曹高忠,等.rh-aFGF卡波姆940凝胶对1型糖尿病大鼠皮肤创伤的修复作用[J].中国药理学通报,2018,34(4):557-62.[3]Yang X X,Hui Q,Cao G Z,et al.The therapeutic effect of rha FGF carbomer 940 gel on wound healing in type I diabetic SD rat models[J].Chin Pharmacol Bull,2018,34(4):557-62.
[4]Chammas N K,Hill R L,Edmonds M E.Increased mortality in diabetic foot ulcer patients:the significance of ulcer type[J].JDiabetes Res,2016,2016:2879809.
[5]Sun Q,Tang D D,Yin E G,et al.Diagnostic significance of serum levels of nerve growth factor and brain derived neurotrophic factor in diabetic peripheral neuropathy[J].Med Sci Monit,2018,24:5943-50.
[6]Chen J C,Lin B B,Hu H W,et al.NGF accelerates cutaneous wound healing by promoting the migration of dermal fibroblasts via the PI3K/Akt-Rac1-JNK and ERK pathways[J].BioMed Res Int,2014,2014:547187.
[7]Fu H D,Wang S,Ge B,et al.Nerve growth factor and substance P may be involved in moist exposed burn ointment-mediated chronic refractory wound healing[J].Exp Ther Med,2018,16(3):1987-93.
[8]Schenck K,Schreurs O,Hayashi K,et al.The role of nerve growth factor(NGF)and its precursor forms in oral wound healing[J].Int J Mol Sci,2017,18(2):386-97.
[9]徐江平,郭海彪,汪海涛,等.鼠神经生长因子对糖尿病大鼠皮肤损伤的促愈合作用[J].湖北理工学院学报,2015,31(3):51-6.[9]Xu J P,Guo H B,Wang H T,et al.Healing effect of mouse nerve growth factor on skin injury of diabetic rat[J].J Hubei Polytechnic Univ,2015,31(3):51-6.
[10]秦迪,张慧杰,杨希营,等.抗氧化肽AOP1对小鼠皮肤烫伤创面愈合修复的影响[J].中国药理学通报,2018,34(2):225-31.[10]Qin D,Zhang H J,Yang X Y,et al.Effect of antioxidant peptide AOP1 on healing repair of skin burns in mice[J].Chin Pharmacol Bull,2018,34(2):225-31.
[11]Goyal S N,Reddy N M,Patil K R,et al.Challenges and issues with streptozotocin-induced diabetes-A clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics[J].Chem-Biol Interact,2016,244:49-63.
[12]Ji Y,Zhang A,Chen X,et al.Sodium humate accelerates cutaneous wound healing by activating TGF-beta/Smads signaling pathway in rats[J].Acta Pharm Sin B,2016,6(2):132-40.
[13]Kruse C R,Singh M,Sorensen J A,et al.The effect of local hyperglycemia on skin cells in vitro and on wound healing in euglycemic rats[J].J Surg Res,2016,206(2):418-26.
[14]Nakamichi M,Akishima-Fukasawa Y,Fujisawa C,et al.Basic fibroblast growth factor induces angiogenic properties of fibrocytes to stimulate vascular formation during wound healing[J].Am JPathol,2016,186(12):3203-16.
[15]Langoni Cassettari L,Colli Rocha Dias P,Natalia Lucchesi A,et al.Continuous electrical current and zinc sulphate administered by transdermal iontophoresis improves skin healing in diabetic rats induced by alloxan:morphological and ultrastructural analysis[J].JDiabetes Res,2014,2014:980232.