摘要
糖尿病创面延迟愈合一直是困扰临床医生的难题,近年来胰岛素的局部应用受到众多学者的重视。胰岛素作为机体最重要的合成激素之一,可加速葡萄糖的氧化和酵解,促进肝的合成与贮存;增加脂肪酸的转运,促进脂肪合成并抑制其分解;促进血液中氨基酸进入细胞内进行蛋白质合成,抑制肝脏和肌肉蛋白质的降解。还具有一定的抗炎及促修复细胞增殖、分化等作用。创面愈合是机体通过自身的再生能力,为恢复其表面的连续性和完整性,维持内环境稳定所进行的一系列修复活动。创面愈合的两大重要参数上皮化和血管化。局部应用胰岛素能使组织细胞主动摄取或扩散获得胰岛素,调节糖类利用及能量产生,并促进氨基酸进入细胞合成蛋白质。更为重要的是,它能加速局部血管化、促进成纤维细胞的生长和胶原合成。本实验从局部应用胰岛素对糖尿病大鼠糖代谢、创面愈合、细胞增殖等不同层面,研究局部应用胰岛素对创面愈合的影响及机制。研究方法通过对糖尿病大鼠创面炎症反应、血管生成、胶原合成、创面内源性表皮生长因子等动态指标来揭示胰岛素的促进创面愈合的作用机制及应用安全性。通过本实验得出以下结果:从胰岛素对血糖水平的影响来看,低剂量治疗组较高剂量治疗组对血糖影响小;胰岛素能够减轻局部炎症反应,促进创面组织中CD34、VEGF的表达,创面新生血管形成增加,羟脯氨酸含量增加,增殖细胞周期提前。促进创面神经生长,应用方法以局部浸润注射效果好。结论:糖尿病鼠创面下局部浸润注射O.1U胰岛素能够加速创面新生血管形成及细胞增殖,促进创面愈合,促进神经生长,减轻感染。对血糖水平无不良影响,是一种安全有效的治疗方法,为进一步向临床推广应用提供了有益的理论依据。
In recent years ,more attention has increasinly been paid to the effect of insulin and glycemia regulation on diabetes wounds, studies indicate that insulin ,one of the most important anabolism hormone , can promote the synthesis of the hephormone and transportation of the glucose ,and increase the synthesis of protein and storage of the lipid in adipocyte. The exogenous insulin is helpful to rectify negative nitrogen balance and promotes the formation of blood vessel. And insulin can also promote the capacity of antiinflammatory and cell multiplication or differentiation etc .Wound healing is a series of recovery activity that the organism maintain the homeostasis and the recovery of superficial succession and integrity depending on its own regeneration capacity . wound recovery is a orderly,step-by-step procedure.it includes a series of stage such as : inflammation; Cellular proliferation; apposition ; tissue re-establishment.. a lot of complicated elements are involve into these stages that including wound coagulation; inflammation; granulation tissue formation ; epithelialization ; blood vessel regeneration ; Neovascularity formation ;Collogen synthesis ;wound contraction. Two important parameters of wound healing are epithelization and vascularization . diabetes results in the periphery arteries scleratheroma that cause extensive small vessels endotheliosis and capillary basement membrane thickening ,which cause the vasomotion dysfunction and reduction of blood flow .Diabetic Chronic ulcer of skin has close relationship with anoxaemia and ischemic condition of tissues. late healed wound of diabetes is a puzzle to us for a long time, three key points that influence the wound healing of diabetes are vessel element ,nerve element and infection element. It is found that Clinical local insulin application can improve the wound healing with little influence on blood glucose level. Inflammatory reaction is a very important part of wound healing . Insulin participates the regulation of many links . decrease the pre-inflammatory cell factor siginficantly ; prevent excessive inflammatory reaction ; restrain the protein degradation of heterophil granulocyte in peripheral blood and spleen. Increase the capacities of celluar tendency and phagocytosis ,and improve the immune level. In theory , local insulin application can cause histiocyte to absorb or diffuse insulin initiatively, to regulate the utilization of carbohydrate and energy production and to promote the amino acids entering the cell to synthesize protein . More importantly, it can speed up the local vascularization and fibroblastic growth and collogen composition. The dosage of insulin and its administration route are discussed at present . In order to identify the mechanism of local insulin usage and its clilical safety , we design this experiment . This study was to investigate the effects of topical application of insulin on glycometabolism ,wound healing、bacterium growth,cell proliferation. we apply the indexes of macroscopic and microcosmic scope . Macroscopic indexes include healing time,healing rate and FB cell numbers and local inflammation reaction . Microcosmic indexes include Angiogenesis and collagen synthesis, endogenous EGF ,CD34,etc to reveal the mechanism and safety of insulin so as to supply the sound theoretical basis for the topical use of insulin on the wound. We get the results that in point of the effect of insulin on the blood glucose,it is obvious safer in small dosage group than that of the large dosage group.topical application of insulin on wound can promote decrease the local inflammation reaction ,promote the expression of CD34、VEGF and neovascularization, increase of HYP, All of anaerobic bacterium and aerobic bacteria on the wound decreased ,especially the anaerobic bacterium. Cell proliferation circle is ahead of schedule ,nerve regeneration also advanced. local infiltration is a better choice for use of insulin .Conclusion : blood vessel , nerve degeneration, infection are three key points for Diabetes gangrene . The micro-organism features of it is the combined infection of anaerobian and aerobe . The results of our research strongly support that the subcutaneous injection of 0.1U insulin into the wounds can speed up the neovascularization and nerve regeneration of the wound and the wound healing, relieve the wound infection. and there is little influence on blood glucose, the topical application of small dosage insulin is effective and safe ,this study can supply the theoretical basis for the clinical application.
引文
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