Chapter . RepairⅣ修复

parenchyma 实质 connective tissue 间质 regeneration healing (scar, fibrosis)

injured cells and tissue

repair

(Regeneration refers to the proliferation of cells and tissues to replace lost structures )

Ⅰ. Control of Normal Cell Proliferation and Tissue Growth

(1). The activity of cell proliferation ( 增生能力 )

Labile cells (continuously dividing tissues )

Surface epithelia, cells of bone marrowhematopoietic tissuesStem cells

Stable cells (Quiescent tissues )

Parenchyma cells of liver, kidneys, and pancreasendothelial cells, lymphocytes, leukocytes

Permanent cells (Nondividing tissues)

Neurons, cardiac muscle, skeletal muscle

Cell-cycle细胞周期

Cyclins-CDKs

A

B

C 、 D 、 E

Stem cells

Gene

2012 Nobel Prize for the discovery that adult cells can be transformed back into embryo-like stem cells that may one day regrow tissue in damaged brains, hearts or other organs.

Sequamous

cell of skin

Embryonic stem cells

(2).The effect of Growth factors

1. EGF: mitogenic for keratinocytes and Fb2. PDGF: chemotactic for PMNs, MΦ, Fb, SMC; stimulates production

of MMPs, Fn, HA, angiogenesis and wound contraction3. bFGF: chemotactic for Fb, mitogenic for Fb and keratinocytes, stimul

ates keratinocyte migration, angiogenesis, matrix deposition4. HGF: stimulates proliferation of epithelial and endothelial cells5. KGF: stimulates keratinocyte migration, proliferation and differentiat

ion6. TGF-: chemotactic for PMNs, MΦ, Lymphocytes, Fb, SMC; stimulat

es TIMP synthesis, keratinocyte migration, angiogenesis and fibroplasia; inhibits production of MMPs and keratinocyte proliferation

7. IL-1: chemotactic for PMNs; stimulation of MMP-1 synthesis8. TNF: activates MΦ, regulates other cytokines

General patterns of intercellular signaling

(3).Cell surface receptors and

signal transduction

system

Ⅱ. Extracellular matrix, ECM细胞外基质

Major components of ECM ： 1.fibrous structural proteins ：

collagen 胶原蛋白

elastin 弹性蛋白 2.adhesive glycoproteins ：

fibronectin 纤连蛋白laminin 层连蛋白

3.proteoglycans and hyaluronan glycosaminoglycan ：粘多糖 heparan sulfate 、 dermatan sulfate

ECM occurs in two basic forms: interstitial matrix and basement membrane.

Roles of the ECM

1. Mechanical support for cell anchorage

2. Control of cell growth

3. Maintenance of cell differentiation

4. Scaffolding for tissue renewal

5. Establishment of tissue microenvironments

6. Storage and presentation of regulatory molecules

(1).granulation tissue肉芽组织

Newly formed capillaries

Proliferation of Fibroblast

Inflammaroty cells

Ⅲ. Repair by Healing with connective tissue结缔组织修复

The formation of granulation tissue is the critical stape in healing

New small blood vessels

( 新生的小血管 )Proliferation of F

b( 成纤维细胞 )

Inflammaroty cells

a) Angiogenesis from pre-existing vessels

2.The process of granulation tissue formation

Angiogenesis from endothelial precursor cells

b) Granulation tissue formation and development

Granulation tissue Fibrous tissue Scar

c. ECM and tissue remodeling

The outcome of repair process is a balance between the synthesis and degradation of ECM

ECM degradated by Matrix metalloproteinase (MMPs,)

①interstitial collagenase ( MMP1, MMP5) Col and ColⅢ②gelatinases (MMP2,MMP9) Col and Col in BMⅣ Ⅴ③stromelysin (MMP3,MMP10, MMP11) proteoglycans fibronectin, Laminin, others

MMPs are inhibited by Tissue inhibitor of matrix metalloproteinase (TIMPs)

TIMP1, TIMP2;

（ 2 ）基质金属蛋白酶 / 基质金属蛋白酶组织抑制因子

matrix metalloproteinases MMPs 主要分三类：

（ 1 ）间质胶原酶如 MMP-1 、 MMP-5 ，降解 Ⅰ型和Ⅲ型胶原；

（ 2 ）明胶酶，包括 MMP-2 、 MMP-9 ，降解 Ⅳ型胶原和Ⅴ型胶原；

（ 3 ）间质溶解素，如 MMP-3 、 MMP-10 及基质水解蛋白等，

主要作用于 ECM 成分的糖蛋白，如 FN 、 LN 等。

基质金属蛋白酶组织抑制因子（ tissue inhibitor of matrix metalloproteinases ， TIMPs ）是 MMPs 特异性的抑制剂，

主要有 TIMP-1 、 TIMP-2 、 TIMP-3 三类。

Ⅳ. wound healing创伤愈合

Healing by first/second intention一期愈合、二期愈合

Cutaneous

Wound

InflammationGranulation Tissue Reepithelialization

Healing

Healing processes:

•Induction of inflammation process (remove damaged and dead tissue)•Proliferation and migration of parenchyma and connective tissue cells•Formation of new blood vessels and granulation tissue•Synthesis of ECM proteins and collagen deposition•Tissue remodeling•Wound contraction•Acquisition of wound strength

Healing by first intention

Operative incision Cut surface is neat and tidy Less infection Invaded and linked by less granulation

tissue and covered by new epithelial cell

Healing by second intention

Large wound, abscess, ulceration Infection or foreign body existing More inflammation Clear the wound by debridement Large amounts of granulation tissue Scar formation

Ⅴ. Factors that influence wound healing影响修复的因素

Systemic factors ：nutrition( 营养 )Metabolic sttus( 代谢状况 )Circulatory sttus( 循环状况 )Hormones( 激素 )

Local factors ：Infection( 感染 )Mechanical factors( 机械磨擦 )Foreign bodies( 异物 )Size, location and type of wound

( 大小、部位、伤口类型）

Complications in cutaneous wound healing（并发症）：

Deficient scar formation 瘢痕形成不足Wound dehiscence( 伤口裂开 )Ulceration （溃疡）

Excessive formation of the repair components 瘢痕形成过度keloid （瘢痕疙瘩）aggressive fibromatoses （侵袭性纤维瘤病）

Formation of contractures 挛缩Deformities of the wound and the surrounding tissue

keloid （瘢痕疙瘩）

1

2

3

Thank you

for your attention ！