细胞生长因子与创伤愈合

创伤愈合是一个复杂的过程,传统将这一过程分为血凝期、炎症期、增值期、组织重构四个相互重叠的时期。多种细胞生长因子参与了这一过程,这些细胞因子包括EGF、bFGF、VEGF、PDGF等。本文就创伤愈合过程以及其涉及的细胞生长因子的生物学特性、创伤时的表达情况、对创面愈合的促进作用、应用前景作一概述。     

Isoniazid and Wound Healing

In non-tuberculous patients with lesions exhibiting a delayed healing process oral isoniazid in doses of 3 mg./kg. was found to be rapidly effective in stimulating the wounded area to produce healthy granulation tissue. The prompt healing of these defects was accomplished by the formation of scar tissue which resisted stress in a superior manner. A topical ointment of 2% isoniazid in eucerin had a similar beneficial effect in patients with indolent skin ulcers who had failed to respond to routine treatment. Epithelialization rapidly ensued once the granulating base was established. A further series of patients with delayed wound healing and failure to respond to antibiotics or isoniazid alone showed satisfactory response when both measures were used simultaneously. It is postulated that isoniazid provides a stimulus to the growth of normal granulation tissue, may promote greater tensile strength in scars, and may be of benefit in antibiotic-resistant infections because of its ability to boost the host''s normal repair mechanisms.     

Murine Model of Wound Healing

Wound healing and repair are the most complex biological processes that occur in human life. After injury, multiple biological pathways become activated. Impaired wound healing, which occurs in diabetic patients for example, can lead to severe unfavorable outcomes such as amputation. There is, therefore, an increasing impetus to develop novel agents that promote wound repair. The testing of these has been limited to large animal models such as swine, which are often impractical. Mice represent the ideal preclinical model, as they are economical and amenable to genetic manipulation, which allows for mechanistic investigation. However, wound healing in a mouse is fundamentally different to that of humans as it primarily occurs via contraction. Our murine model overcomes this by incorporating a splint around the wound. By splinting the wound, the repair process is then dependent on epithelialization, cellular proliferation and angiogenesis, which closely mirror the biological processes of human wound healing. Whilst requiring consistency and care, this murine model does not involve complicated surgical techniques and allows for the robust testing of promising agents that may, for example, promote angiogenesis or inhibit inflammation. Furthermore, each mouse acts as its own control as two wounds are prepared, enabling the application of both the test compound and the vehicle control on the same animal. In conclusion, we demonstrate a practical, easy-to-learn, and robust model of wound healing, which is comparable to that of humans.     

瘦蛋白与皮肤创伤愈合

自1994年瘦蛋白（leptin）被发现以来,其生理作用得到广泛的研究。近年的研究表明,在高等动物的皮肤创伤愈合过程中,胶原与血管的生成、肉芽组织与上皮的再生以及组织的重建等因子,对皮肤的创伤愈合发挥着至关重要的作用,了解瘦蛋白与上述因子之间的相互关系与作用机制,有助于指导治疗,改善预后。     

MiRNA 与皮肤伤口愈合

MiRNA是真核生物体内约由22个核苷酸组成的内源性非编码单链RNA,可调节基因转录。它通过其5’非翻译区(UTR)与目标mRNA的3’端非翻译区相结合,从而抑制后者的转录后翻译和降解,进而调节一系列生物学过程,包括生物体生长、发育和疾病等。研究表明,miRNA在干细胞分化、肿瘤形成、血管发生、内耳形成等过程中均发挥重要作用,已成为调节生物学过程的核心因子。伤口愈合是一个与多种类型细胞、细胞因子及细胞外基质相关的过程,它受机体多种因素紧密调控。伤口愈合过程一般被分为三个阶段:炎症反应期,肉芽生长期和组织重建期。已有大量证据证实miRNA在皮肤创伤愈合过程中发挥重要作用,并且miRNA在不同的愈合阶段发挥不同的作用。本文就miRNA在皮肤形态、胎儿无痕愈合及成人伤口愈合各环节中的作用做一综述。     

Thrombomodulin Promotes Corneal Epithelial Wound Healing

Purpose

To determine the role of thrombomodulin (TM) in corneal epithelial wound healing, and to investigate whether recombinant TM epidermal growth factor-like domain plus serine/threonine-rich domain (rTMD23) has therapeutic potential in corneal epithelial wound healing.

Methods

TM localization and expression in the murine cornea were examined by immunofluorescence staining. TM expression after injury was also studied. The effect of rTMD23 on corneal wound healing was evaluated by in vitro and in vivo assays.

Results

TM was expressed in the cornea in normal adult mice. TM expression increased in the early phase of wound healing and decreased after wound recovery. In the in vitro study, platelet-derived growth factor-BB (PDGF-BB) induced TM expression in murine corneal epithelial cells by mediating E26 transformation-specific sequence-1 (Ets-1) via the mammalian target of rapamycin (mTOR) signaling pathway. The administration of rTMD23 increased the rate of corneal epithelial wound healing.

Conclusions

TM expression in corneal epithelium was modulated during the corneal wound healing process, and may be regulated by PDGF-BB. In addition, rTMD23 has therapeutic potential in corneal injury.