皮肤损伤的修复课件.ppt

1、 讲 授 人：金以超 讲师 纤维性修复纤维性修复fibroplasiafibroplasia 皮肤损伤的修复修复repair 再生 Regeneration 纤维性修复不能由再生修复的损伤，通过不能由再生修复的损伤，通过肉芽组织肉芽组织增生填补缺损并转化为增生填补缺损并转化为瘢痕组织瘢痕组织的过程的过程。肉芽组织肉芽组织 Granulation tissueGranulation tissue一、概念：一、概念： GranGranulation ulation tissuetissue肉芽组织的结构：肉芽组织的结构： 镜下：镜下： 二、肉芽组织的形态二、肉芽组织的形态毛细血管多与垂直创面，在创

2、口表面形成袢状弯曲毛细血管多与垂直创面，在创口表面形成袢状弯曲Gross appearance： 红色颗粒样，柔软湿润，触之易出血红色颗粒样，柔软湿润，触之易出血三、肉芽组织的功能三、肉芽组织的功能3、填补连接伤口或其他缺损、填补连接伤口或其他缺损 1、抗感染及保护创面、抗感染及保护创面 2、机化血凝块、坏死组织及其他异物、机化血凝块、坏死组织及其他异物 健康肉芽不良肉芽四、肉芽组织的结局四、肉芽组织的结局新生的毛细血管新生的毛细血管 增生的纤维母细胞增生的纤维母细胞一定量的炎性细胞一定量的炎性细胞小动脉、小静脉闭合、消失闭合、消失胶原纤维、胶原纤维、纤维细胞纤维细胞纤维结缔组织纤维结缔组织瘢

3、痕组织（瘢痕组织（scar tissue)吸收、消散吸收、消散Granulation tissueScar tissue五、瘢痕组织对机体的影响五、瘢痕组织对机体的影响利利1.保持组织器官保持组织器官完整性完整性2.保持组织器官保持组织器官坚固性坚固性弊弊1.瘢痕收缩瘢痕收缩2.瘢痕粘瘢痕粘连连3.瘢痕疙瘩瘢痕疙瘩(keloid)4.瘢痕膨出瘢痕膨出六、肉芽组织和瘢痕 组织的形成过程及机制血管生成血管生成成纤维细胞增殖和迁移成纤维细胞增殖和迁移细胞外基质成分的积聚和成纤维组织的重建细胞外基质成分的积聚和成纤维组织的重建（一）血管生成的过程从发生学和组织学的观点出发，把广义的血管新生（neova

4、scularization）分为两种类型:endothelial progenitor cell , EPCangioblast最近研究证明，血液中存在EPC，它参与重症缺血区域血管的形成，所以病理状态下的血管生成，既包括广义的血管形成，又有狭义的血管生成。血管形成（血管形成（vasculogenesis）血管生成（血管生成（angiogenesis）出芽方式的血管生成及包含的步骤：Vasodilation - NO Increased permeability - VEGF Proliferation of endothelial cells just behind the leading

5、front of migrating cells Remodeling into capillary tubes Migration of endothelial cells toward the area of tissue injury Suppression of endothelial proliferation and migration and deposition of the basement membrane Recruitment of periendothelial cells (pericytes for small capillaries and smooth mus

6、cle cells for larger vessels) to form the mature vesselThe process of angiogenesis involves a variety of growth factors, cellcell interactions, interactions with ECM proteins, and tissue enzymes.1、Growth Factors Involved in Angiogenesis VEGF Basic Fibroblast Growth Factor (bFGF) AngiopoietinsVEGF st

7、imulates both migration and proliferation of endothelial cells, initiates the process of capillary sprouting in angiogenesis.VEGF contributes to the formation of the vascular lumen.bFGF-2 participates in angiogenesis m o s t l y b y s t i m u l a t i n g t h e proliferation of endothelial cells. It

8、also promotes the migration of macrophages and fibroblasts to the damaged area, and stimulates epithelial cell migration to cover epidermal wounds.Ang1 and Ang2 are growth factors that play a role in angiogenesis and the structural maturation of new vessels. Matrix metalloproteinases (MMPs) degrade

9、the ECM to permit remodeling and extension of the vascular tube. 2、ECM proteins Participating in the process of vessel sprouting in angio- genesis. Providing the scaffold for vessel growth. Integrins , especially 3 , have important role in formation and stability of vessel. Activation of Fibroblasts

10、 and Deposition of ECM Two steps: (1) Migration and proliferation of fibroblasts into the site of injuryMany growth factors, including PDGF, FGF-2, and TGF-, drive fibroblasts to synthesize connective tissue proteins .The major source of these factors is inflammatory cells, particularly macrophages,

11、 which are present at sites of injury and in granulation tissue.Proliferating fibroblasts and new vessels Fibroblasts synthetic Deposition of ECM Collagen synthesis is critical to the development of strength in a healing wound site.Collagen synthesis by fibroblasts begins early in wound healing (day

12、s 3 to 5) and continues for several weeks, depending on the size of the wound. Net collagen accumulation depends not only on increased synthesis but also on diminished collagen degradation .(2) Deposition of ECM proteinsUltimately, the granulation tissue evolves into a scar composed of largely inact

13、ive, spindle-shaped fibroblasts, dense collagen, fragments of elastic tissue, and other ECM components . As the scar matures, there is progressive vascular regression, which eventually transforms the highly vascularized granulation tissue into a pale, largely avascular scar.Growth Factors Involved i

14、n ECM Deposition and Scar FormationTGF- stimulates the production of collagen, fibronectin, and proteoglycans, and it inhibits collagen degradation by both decreasing proteinase activity and increasing the activity of tissue inhibitors of proteinases . PDGF causes migration and proliferation of fibr

15、oblasts and smooth muscle cells and may contribute to the migration of macrophages .Cytokines may also function as growth factors and participate in ECM deposition and scar formation. IL-1 and IL-13 act on fibroblasts to stimulate collagen synthesis, and can enhance the proliferation and migration of fibroblasts.Remodeling of Connective Tissue A balance between synthesis and degradation of ECM proteins.The degradation of collagens and other ECM components is accomplished by a family of matrix metalloproteinases (MMPs)Tissue inhibitors of metalloproteinases (TIMP)总结和展望How to deal with scar？