糖尿病裸鼠的皮肤组织改变及其与创面愈合的相关性

Histological changes of skin and its relationship with wound healing in diabetic nude mice

目的研究糖尿病裸鼠的皮肤组织改变及其与皮肤创面愈合的相关性。方法采用150 mg/kg链脲佐菌素(STZ)一次性腹腔注射建立糖尿病裸鼠模型。对正常对照组裸鼠(n=20)和诱导成模后4周的糖尿病裸鼠(n=20)分别切取背部直径为1.8 cm的全层皮肤。采用苏木精-伊红(HE)染色,观察裸鼠皮肤的组织学改变并测量真皮层和表皮层厚度。采用苦味酸天狼猩红染色并分析相对胶原含量;应用氧化酶法测量皮肤组织糖含量。于术后第3、5、7、14和21天观察创面的愈合率。结果糖尿病组裸鼠的皮肤真皮层和表皮层厚度较正常对照组明显变薄,真皮层相对胶原含量也明显少于正常对照组,差异均有统计学意义(P<0.05或P<0.01)。糖尿病组裸鼠的血糖浓度和皮肤糖含量均高于正常对照组,差异有统计学意义(P<0.01);皮肤组织糖含量与血糖浓度呈正相关(r=0.951,P<0.01)。糖尿病组裸鼠在术后第3、5、7、14和21天的创面愈合率显著低于正常对照组,差异有统计学意义(P<0.01)。结论应用STZ诱导的糖尿病裸鼠模型的皮肤组织改变明显,这些改变可能与局部糖基化终末产物蓄积,导致糖尿病皮肤创面不易愈合有关。

Objective To observe the histological changes of skin and explore its relationship with wound healing in diabetic nude mice. Methods Diabetic nude mice models were established by intraperitoneal injection of 150 mg/kg STZ.Full-thickness skin of 1.8 cm in diameter was obtained from the dorsum of normal control rats（n=20） and diabetic nude mice（n=20） 4 weeks after model establishment.HE staining was used to observe the histological changes of skin,and the thickness of dermis and epidermis was measured.Picrosirius red staining was employed to analyse the relative content of collagen in dermis.The cutaneous content of glucose was determined by glucose oxidase method.The wound closure rates were calculated 3 d,5 d,7 d,14 d and 21 d after operation. Results The dermis and epidermis of diabetic nude mice were significantly thinner than those of normal controls（P0.05）,and the relative content of collagen in dermis of diabetic nude mice was significantly lower than that of normal controls（P0.01）.The concentration of blood glucose and cutaneous content of glucose of diabetic nude mice were significantly higher than those of normal controls（P0.01）,and there was a positive correlation between cutaneous content of glucose and concentration of blood glucose（r=0.951,P0.01）.The wound closure rates of diabetic nude mice 3 d,5 d,7 d,14 d and 21 d after operation were significantly lower than those in normal controls（P0.01）. Conclusion There are significant histological changes of skin in diabetic nude mice induced by STZ,and these changes may be related to the accumulation of advanced glycation end products,which may lead to the impaired wound healing.