封闭负压引流技术对人慢性创面中基质金属蛋白酶以及其调控因素的影响
|
摘要
慢性创面的治疗是整形外科的一个十分棘手的问题，给患者经济上、心理上都造成了极大的负担。封闭负压引流技术(Vacuum-Assisted Closure, VAC)的出现给慢性创面的治疗带来了新的希望，许多临床以及实验研究表明VAC可以提高肉芽创面血流量，促进创面细菌、坏死组织以及引流液清除，从而可以显著提高急、慢性创面愈合速度。目前VAC技术已在国外广泛应用，在国内正在逐渐推广，但国内外有关VAC促进慢性创面愈合的机理研究还刚刚起步，很不系统，相关报道较少，特别是对于VAC应用后ECM发生的变化还未见报道。而且就慢性创面本身而言，它的形成机制还远没有阐述清楚。本实验以ECM领域中的重要成分MMPs为主要研究内容，分析VAC前后MMPs的含量、定位、活性发生的变化，同时也对MMPs的几种调控因素的变化进行了观察，从此方面部分地阐明VAC促进慢性创面的机理，而且也可部分阐明慢性创面的形成机制。
本实验以我科收治的13例慢性创面患者为研究对象(见附表)，其中压力性溃疡5例，静脉性溃疡6例，外伤后皮肤缺损1例，乳癌术后伤口迁延不愈1例，分别给予—120mmHg的VAC治疗，从以下六个部分进行观察：
第一部分：对9例慢性创面患者给予VAC治疗(-120mmHg压力)，分别于治疗前和治疗后1、4、7天切取创面中央肉芽组织，提取总RNA，
第四军医大学博士学位论文
利用 RT－PCR方法测定 MMP－l、MMP－2J 3和 TIW．l、TIMPZmRNA
的表达情况，并对其半定量结果进行统计学分析。结果发现：MMP－l。
13mRNA在VAC治疗后表达下降，以MW上 下降趋势尤为明显。
h4MI）－2 mRNA表达呈现波动，但总体为下降趋势；在VAC治疗前，
检测不到TIMP4、ZInRNA的表达，应用VAC后，出现了两者的表达，
而且随时间的延长，TIMP－l、ZmRNA的表达呈现明显的上升趋势。
第H部分：对9例慢性创面患者给予VAC治疗～120mmHg人分别于
治疗前和治疗后l、4、7天切取创面创缘组织，用免疫组织化学方法
观察 MW上、2、8、9、13，TI衅上、2的蛋白分布动态变化。结果
发现：总体上随 VAC作用时间延长，MMP．1、2、8、9、13的表达渐
弱，而TIMP－l、2的表达增多。VAC治疗后MMi－1在表皮角化层表
达增加，真皮层变化不很显著；A4MP－8不仅在炎细胞周围表达，而且
在表皮中也有表达，VAC治疗前后变化不很明显，真皮染色渐淡；VAC
治疗前表皮角化层有MMPq 的染色，治疗后不仅表皮染色消失，而
且主要是真皮弥漫性分布变淡，越接近创缘表达越减少；MMP．2则角
化层染色变淡，基底层染色加深；h4Nl，－9则表皮染色在7天时加深明
显；TM上、2在VAC治疗前基本无表达，治疗后表真皮均出现表达，
最深在颗粒细胞层，血管壁周围染色加深。
第三部分：收集4例急性创面在术后1，2，3天的创面引流液（乳癌
术后）和 4例慢性创面在VAC治疗前以及治疗后 2，4，6天的创面渗
出液，利用酶谱分析的方法，观察各时间点的渗出液对可溶性＊型胶
原的降解情况，同时应用强力霉素抑制实验来分析渗出液中胶原酶的
主要类型。结果发现：急性创面引流液可以部分降解＊型胶原，但降
解量变化不大；而慢性创面渗出液中的胶原酶活性较高，VAC治疗前
基本将＊型胶原全部降解，而且随时间推移降解减少，胶原酶活性下
降，强力霉素抑制实验证明在 100w浓度时对胶原酶活性无抑制，在
4
第四军医大学博士学位论文
600PM浓度时出现部分抑制。
第四部分：取8例急性创面在术后1、2、3天的创面引流液（乳癌术
后），同时收集 11例慢性创面在 VAC治疗前以及治疗后 1、3、5、7
天的创面渗出液，利用夹心ELISA法，分别测定其中T’－a－．口的含量
并进行动态的观察与比较。结果发现：急性创面引流液中TNF－口水平
较低，第2天含量有所下降，第3天再度回升。静脉性溃疡及压力性
溃疡的创面渗出液中在治疗前TNF－口水平较高（以前者更甚），治疗
后均逐步下降，前者在治疗后第1、3、5天下降最为显著o功05人
后者在治疗后第5和第7天下降最为显著o＜0刀5）。
第五部分：对5例慢‘性创面患者给予VA C治疗～1201：Tll：lirlg压力人
分别于吸引前以及吸引后1，4，7天切取创缘组织，固定、包埋、切
片后应用免疫组织化学方法观察C－fos蛋白表达的动态变化。结果发
现：负压吸引前，。－fos阳性细胞表达较多，主要分布在表皮基底以及
真皮浅层中的成纤维细胞及炎性细胞的胞核中，少部分胞浆中亦存在。
随负压时间的延长，C－fos阳性细胞渐少，主要分布在真皮层的成纤维
细胞胞核中，至第7天己罕见c．fos蛋白的表达。
第六部分：取8例急性创面在术后1，2，3天的创面引流液（乳癌术
后），同时收集 11例慢性创面在 VAC治疗前以及治疗后 1，3，5，7
天的创面渗出液，利用放射兔疫测定的方法，分别测定其中HA的含
量并进行动态的观察?
Effect of the Vacuum-Assisted Closure on matrix metalloproteinases and its regulated factors in human
chronic wound Doctoral candidate ShiBing
Advisor Chen Shao-zong
Therapy to chronic wound, which results in very heavier burden both in economy and psychology to patients, is a very sophisticated problem of plastic surgery.
The appearance of VAC brought about a new hope toward the treatment of chronic wound. Many experimental and clinical studies suggested that VAC could promote acute and chronic wound healing owing to its increasing the blood flow in granulation wound, facilitating the remove of wound bacteria, necrosis tissue and drainage fluid. At present, VAC has been applying exclusively in foreign countries and it is being popularized gradually in our country. However, study on mechanisms of VAC promoting chronic wound healing has not been carried through systematically and relative reports are very seldom, especially variation of ECM components before and after VAC therapy had no report. Furthermore, as far as chronic wound itself, the potential formative mechanism has so far been disclosed clearly. MMP, a very important component of ECM was used as main content in our experiment. We observed the changes of value, localization and activity of MMPs, also we observed the changes of some regulated factors relative to MMPs,
so as
to partly explain the mechanisms of VAC promoting wound healing and of chronic wound formation.
13 patients (5 cases pressure sore, 6 cases venous ulcer, 1 case skin defect after trauma, 1 case non-healing wound after operation of breast cancer) hospitalized in our department were treated with VAC (-120mmHg). We studied as follows in six parts:
Parti: Using RT-PCR, we determined the expressions of MMP-1, 2,13
and TIMP-1, 2 mRNA in granulation tissues from 9 patients with chronic wounds before and l,4,7days after treatment with VAC .We found that MMP-1, 13 mRNA took on an obvious tendency of decrease with the steepest variations in MMP-13. Although there were contradictory results in MMP-2mRNA, the decrease tendency was the same. There was no expression of TIMP-1, 2 mRNA before VAC. But TIMP-1, 2mRNA began to express after VAC as well as taking on obvious tendencies of increase with the time going.
Part2: Using immunohistochemistry, we observed the variations of
MMP-1, 2, 8, 9, 13, TIMP-1, 2 protein in margin tissues from 9 patients with chronic wounds before and after 1, 4, 7 days after treatment with VAC. We found that in general, expression of MMP-1, 2, 8, 9, 13, became less and of TIMP-1, 2 became strong with time going after VAC. More MMP-1 expressions were found in keratinocyte layer with no obvious changes in dermis after VAC. There was less stain in keratinocyte layer and more stain in basal layer in MMP-2 and distinctly more stain in epidermis in MMP-9 after VAC. Not only can we observe the expressions of MMP-8 around inflammatory cells, but also can observe the expressions
in epidermis with no changes before and after VAC. But less expression can be found in dermis after VAC. Before VAC, MMP-13 stain can be found in keratinocyte layer, but becoming disappear after VAC. Mainly changes were that stain became less in dermis after VAC with becoming less and less approaching the wound margin. Before VAC, no TIMP-1, 2 expressions can be found, but expressions became stronger after VAC as well as stain being found around blood vessels.
Part3: Collecting exudates of 4 acute wound (postoperative breast cancer)
at day 1, 2, 3 postoperatively and 4 chronic wounds before and 2,4,6 days after treatment of VAC, we observed the type-Ill collagen degradation from exudates of every timepoint with zymography as well as the type of collagenase in exudates using doxycycline inhibition test. We found that drainage fluids from acute wound might degrade type-Ill collagen partly with no changes at day 1, 2, 3. There was high collagenase activity in chronic woud exudates. Exudates from patients before treatment with VAC co
本实验以我科收治的13例慢性创面患者为研究对象(见附表)，其中压力性溃疡5例，静脉性溃疡6例，外伤后皮肤缺损1例，乳癌术后伤口迁延不愈1例，分别给予—120mmHg的VAC治疗，从以下六个部分进行观察：
第一部分：对9例慢性创面患者给予VAC治疗(-120mmHg压力)，分别于治疗前和治疗后1、4、7天切取创面中央肉芽组织，提取总RNA，
第四军医大学博士学位论文
利用 RT－PCR方法测定 MMP－l、MMP－2J 3和 TIW．l、TIMPZmRNA
的表达情况，并对其半定量结果进行统计学分析。结果发现：MMP－l。
13mRNA在VAC治疗后表达下降，以MW上 下降趋势尤为明显。
h4MI）－2 mRNA表达呈现波动，但总体为下降趋势；在VAC治疗前，
检测不到TIMP4、ZInRNA的表达，应用VAC后，出现了两者的表达，
而且随时间的延长，TIMP－l、ZmRNA的表达呈现明显的上升趋势。
第H部分：对9例慢性创面患者给予VAC治疗～120mmHg人分别于
治疗前和治疗后l、4、7天切取创面创缘组织，用免疫组织化学方法
观察 MW上、2、8、9、13，TI衅上、2的蛋白分布动态变化。结果
发现：总体上随 VAC作用时间延长，MMP．1、2、8、9、13的表达渐
弱，而TIMP－l、2的表达增多。VAC治疗后MMi－1在表皮角化层表
达增加，真皮层变化不很显著；A4MP－8不仅在炎细胞周围表达，而且
在表皮中也有表达，VAC治疗前后变化不很明显，真皮染色渐淡；VAC
治疗前表皮角化层有MMPq 的染色，治疗后不仅表皮染色消失，而
且主要是真皮弥漫性分布变淡，越接近创缘表达越减少；MMP．2则角
化层染色变淡，基底层染色加深；h4Nl，－9则表皮染色在7天时加深明
显；TM上、2在VAC治疗前基本无表达，治疗后表真皮均出现表达，
最深在颗粒细胞层，血管壁周围染色加深。
第三部分：收集4例急性创面在术后1，2，3天的创面引流液（乳癌
术后）和 4例慢性创面在VAC治疗前以及治疗后 2，4，6天的创面渗
出液，利用酶谱分析的方法，观察各时间点的渗出液对可溶性＊型胶
原的降解情况，同时应用强力霉素抑制实验来分析渗出液中胶原酶的
主要类型。结果发现：急性创面引流液可以部分降解＊型胶原，但降
解量变化不大；而慢性创面渗出液中的胶原酶活性较高，VAC治疗前
基本将＊型胶原全部降解，而且随时间推移降解减少，胶原酶活性下
降，强力霉素抑制实验证明在 100w浓度时对胶原酶活性无抑制，在
4
第四军医大学博士学位论文
600PM浓度时出现部分抑制。
第四部分：取8例急性创面在术后1、2、3天的创面引流液（乳癌术
后），同时收集 11例慢性创面在 VAC治疗前以及治疗后 1、3、5、7
天的创面渗出液，利用夹心ELISA法，分别测定其中T’－a－．口的含量
并进行动态的观察与比较。结果发现：急性创面引流液中TNF－口水平
较低，第2天含量有所下降，第3天再度回升。静脉性溃疡及压力性
溃疡的创面渗出液中在治疗前TNF－口水平较高（以前者更甚），治疗
后均逐步下降，前者在治疗后第1、3、5天下降最为显著o功05人
后者在治疗后第5和第7天下降最为显著o＜0刀5）。
第五部分：对5例慢‘性创面患者给予VA C治疗～1201：Tll：lirlg压力人
分别于吸引前以及吸引后1，4，7天切取创缘组织，固定、包埋、切
片后应用免疫组织化学方法观察C－fos蛋白表达的动态变化。结果发
现：负压吸引前，。－fos阳性细胞表达较多，主要分布在表皮基底以及
真皮浅层中的成纤维细胞及炎性细胞的胞核中，少部分胞浆中亦存在。
随负压时间的延长，C－fos阳性细胞渐少，主要分布在真皮层的成纤维
细胞胞核中，至第7天己罕见c．fos蛋白的表达。
第六部分：取8例急性创面在术后1，2，3天的创面引流液（乳癌术
后），同时收集 11例慢性创面在 VAC治疗前以及治疗后 1，3，5，7
天的创面渗出液，利用放射兔疫测定的方法，分别测定其中HA的含
量并进行动态的观察?
Effect of the Vacuum-Assisted Closure on matrix metalloproteinases and its regulated factors in human
chronic wound Doctoral candidate ShiBing
Advisor Chen Shao-zong
Therapy to chronic wound, which results in very heavier burden both in economy and psychology to patients, is a very sophisticated problem of plastic surgery.
The appearance of VAC brought about a new hope toward the treatment of chronic wound. Many experimental and clinical studies suggested that VAC could promote acute and chronic wound healing owing to its increasing the blood flow in granulation wound, facilitating the remove of wound bacteria, necrosis tissue and drainage fluid. At present, VAC has been applying exclusively in foreign countries and it is being popularized gradually in our country. However, study on mechanisms of VAC promoting chronic wound healing has not been carried through systematically and relative reports are very seldom, especially variation of ECM components before and after VAC therapy had no report. Furthermore, as far as chronic wound itself, the potential formative mechanism has so far been disclosed clearly. MMP, a very important component of ECM was used as main content in our experiment. We observed the changes of value, localization and activity of MMPs, also we observed the changes of some regulated factors relative to MMPs,
so as
to partly explain the mechanisms of VAC promoting wound healing and of chronic wound formation.
13 patients (5 cases pressure sore, 6 cases venous ulcer, 1 case skin defect after trauma, 1 case non-healing wound after operation of breast cancer) hospitalized in our department were treated with VAC (-120mmHg). We studied as follows in six parts:
Parti: Using RT-PCR, we determined the expressions of MMP-1, 2,13
and TIMP-1, 2 mRNA in granulation tissues from 9 patients with chronic wounds before and l,4,7days after treatment with VAC .We found that MMP-1, 13 mRNA took on an obvious tendency of decrease with the steepest variations in MMP-13. Although there were contradictory results in MMP-2mRNA, the decrease tendency was the same. There was no expression of TIMP-1, 2 mRNA before VAC. But TIMP-1, 2mRNA began to express after VAC as well as taking on obvious tendencies of increase with the time going.
Part2: Using immunohistochemistry, we observed the variations of
MMP-1, 2, 8, 9, 13, TIMP-1, 2 protein in margin tissues from 9 patients with chronic wounds before and after 1, 4, 7 days after treatment with VAC. We found that in general, expression of MMP-1, 2, 8, 9, 13, became less and of TIMP-1, 2 became strong with time going after VAC. More MMP-1 expressions were found in keratinocyte layer with no obvious changes in dermis after VAC. There was less stain in keratinocyte layer and more stain in basal layer in MMP-2 and distinctly more stain in epidermis in MMP-9 after VAC. Not only can we observe the expressions of MMP-8 around inflammatory cells, but also can observe the expressions
in epidermis with no changes before and after VAC. But less expression can be found in dermis after VAC. Before VAC, MMP-13 stain can be found in keratinocyte layer, but becoming disappear after VAC. Mainly changes were that stain became less in dermis after VAC with becoming less and less approaching the wound margin. Before VAC, no TIMP-1, 2 expressions can be found, but expressions became stronger after VAC as well as stain being found around blood vessels.
Part3: Collecting exudates of 4 acute wound (postoperative breast cancer)
at day 1, 2, 3 postoperatively and 4 chronic wounds before and 2,4,6 days after treatment of VAC, we observed the type-Ill collagen degradation from exudates of every timepoint with zymography as well as the type of collagenase in exudates using doxycycline inhibition test. We found that drainage fluids from acute wound might degrade type-Ill collagen partly with no changes at day 1, 2, 3. There was high collagenase activity in chronic woud exudates. Exudates from patients before treatment with VAC co
引文
1. Lazarus GS, Cooper DM, Knighton DR, et al.Definitions and guidelines for assessment of wounds and evaluation of healing. Arch Dermatol. 1994; 130:489-493
2. Kirsner RS, Eaglstein WH. The wound healing process. Dermatol Clin. 1993; 11:629-640
3. Fajardo LF, Berthrong M. Radiation injury in Surgical pathology Ⅲ: Salivary glands, pancreas and skin. Am J Surg Pathol. 1981; 5:279-296
4. Hunt TK, Niniikoski J, Zederfeldt BH, et al. Oxygen in wound healing enhancement: Cellular effects of oxygen. In Davis JC, Hunt TK (Eds): Hyperbaric Oxygen Therapy. Kensington, Maryland, Undersea Medical Society, 1977; 111-122
5. Niniikkoski J. Oxygen and wound healing. Clin Plast Surg. 1977; 4:361-374
6. Storch TG, Talley GD. Oxygen concentration regulates the proliferative response of tumor fibroblasts to serum and growth factors. Exp Cell Res. 1988; 175:317-325
7. Ramasastry SS. Chronic problem wounds. Clin in Plast Surg. 1998; 25(3): 367-396
8. Robson MC. Wound infection: a failure of wound healing used by an imbalance of bacteria. Surg Clin North Am. 1997; 77:650
9. Tobin GR. Wound repair: biologic foundations and clinical considerations. In: Richardson JD, Polk HC Jr, Flint LM Jr (eds). Inma: Clinical Care and pathophysiology. Chicago, IL: earbook local Publishers 1987; 213-26
10. Clore JN, Cohen IK, Diegelmann RF. Quantitation of collagen types Ⅲ and Ⅰ during wound healing in rat skin. Proc Soc Exp Bilo Med. 1979; 161:337-340
11. Gay S, Vijanto J, Raekallio J, et al.Collagen types in early phases of wound healing in children. Acta Chir Scand. 1978; 144:205-211
12. Madden JW, Peacock EE. Studies on the biology of collagen during wound healing: Rate of collagen synthesis and deposition in cutaneous wounds of the rat. Surgery 1968; 64:288-294
13. Clark RA. Cutaneous tissue repair: Basic biologic considerations. J Am Acad Dermatol 1985; 13:701-725
14. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998; 176(Suppl 2A): 26S-38S
15. Nwomeh BC, Yager DR, Cohen IK. Physiology of the chronic wound Clinics in Plastic surgery. 1998; 25: 341-356
16. Stadelmann WK, Digenis AG, Tobin GR. Impediments to wound healing. Am J Surg. 1998; 176(Supple 2A): 39S-47S
17. Hunt TK, Zederfeldt BH, Goldstick TK, et al.Tissue oxygen tension during controlled hemorrhage. Surgical Forum. 1967; 18:3-4
18. Hunt TK, Pai MP. The effect of varying ambient oxygen tension on wound metabolism and collagen synthesis. Surg Gynecol Obstet. 1972; 135:561-566
19. Niniikkoski J. Effect of oxygen supply on wound healing and formation of granulation tissue. Acta Physiol Scand. 1969; 3341 (suppl): 71-72
20. Stephens FO, Hunt TK. Effect of changes in impaired oxygen and carbon dioxide tensions on wound tensile strength: An experimental study. Ann Surg. 1971; 173:515-519
21. Hammarlund C, Sundberg T. Hyperbaric oxygen reduced size of chronic leg ulcers: A randomized double-blind study. Plast Reconstr Surg. 1994; 93:829-833
22. Hohn DC, Hunt TK. Oxidative metabolism and antimicrobial activity of rabbit phagocyte cells from wounds and from peripheral blood. Surgical Forum. 1975; 26:85-87
23. Hunt TK, Linsey M, Arislis G, et al.The effect of ambient oxygen tension on wound infection. Ann Surg. 1975; 181:35-39
24. Wagner VH, Keagy AA, Kottb MM, et al.Noninvasive determination of healing of major lower extremity amputations: The combined role of clinical Judgement. J Vasc Surg. 1988; 8:703-710
25. Sheffield PJ: Tissue oxygen measurement with respect to soft tissue wound healing with normobaric and hyperbaric oxygen. Hyperbaric Oxygen Rev. 1955; 6:18-46
26. Falanga V, Grinnell F, Gilchrest B, et al.Experimental approaches to chronic wounds. Wound Repair and Regeneration. 1995; 3: 132-140
27. Falanga V, Kirsner RS. Low oxygen stimulates proliferation of fibroblasts seeded as single cells. J Cell Physiol. 1993; 154:506-510,
28. Knighton DR, Hunt TK, Scheuenstuhl H, et al.Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 1983; 221:1283-1285
29. Falanga V, Qian SW, Danielporu D, et al.Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts. J Invest Dermatol. 1992; 97:634-637
30. Kourembanas S, Harman RL, Faller DV. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J Clin Invest. 1990; 86:670-674
31. Jorgensen LN, Kallehave F, Karlsmark T, et al.Reduced collagen accumulation after major surgery. Br J Surg. 1996; 83:1591-1594
32. Hueghan C, Grisils G, Hunt TK. The effect of anemia on wound healing. Ann Surg. 1974; 179:163-167
33. Stenberg BD, Phillips LG, Hodanson JA, et al. Effect of fibroblast growth factor
on the inhibition of contraction causes bacteria. J Surg Res. 1991; 50:47-50
34. Hayward P, Hokanson J, Heggers J, et al. Fibroblast grow factor reverses the bacterial retardation of wound contraction. Ann Surg. 1992; 163:288-293
35. Robson MC, Stenberg BD, Heggers JD. Wound healing alterations caused by bacteria. Clin Plast Surg. 1990; 3:485-492
36. Robson MC.Infection in the surgical patients: an imbalance the normal equilibrium. Clin Plast Surg. 1979; 6:493-503
37. Robson MC, Krizek TK, Heggers JP. Biology of surgical infection. Medical Publishers, 1973:1-62
38. Krizek TK, Robson MC, Kho E. Bacterial growth and skin survival. Surg Forum. 1967; 18:518-519
39. Thomson PD, Smith-DJ J. What is infection? Am J Surg. 1994; 167 (suppl): 7-10
40. Eriksson G, Eklund AE, Kallings LO. The clinical significance of bacterial growth in venous leg ulcers. Scand J Infect Dis. 1984; 6:175-180
41. Van RL, Brown D, Friedman S, et al.Multicenter clinical evaluation of a hydrocolloid dressing for leg ulcers. 1985; 35:173-176
42. Friedman SJ, Su WP. Management of leg ulcers with hydrocolloid occlusive dressing. Arch Dermatol. 1984; 120:1329-1336
43. Gilchrist B, Reed C. The bacteriology of chronic venous ulcers treated with occlusive hydrocolloid dressings. Br J Dermatol. 1989; 121:337-344
44. Steed DL.The Diabetic Ulcer Study Group. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg. 1995; 21:81
45. Greenhalgh DG. The role of growth factors in wound healing. J Trauma. 1996; 41: 159-167
46. Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg. 1993; 165:729-737
47. Bennett NT, Schultz GS. Growth factors and wound healing: part Ⅱ. Role in normal and chronic wound healing. Am J Surg. 1993; 166:74-81
48. Katz MH, Alvarez AF, Kirsner RS, et al.Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth. J Am Acad Dermatol. 1991; 25:1054-1058
49. Cooper DM, Yu EZ, Hennessey P, et al.Determination of endogenous cytokines in chronic wounds. Ann Surg. 1994; 219:688-691
50. Schmid P, Cox DA, Bilbe G, et al. TGF-βs and TGF-β type Ⅱ receptor in human epidermis: Differential expression in acute and chronic skin wounds. J Patrol. 1993; 171:191-197
51. Beer HD, Longaker MT, Erner S. Reduced expression of PDGF and PDGF
receptors during impaired wound healing. J Invest Dermatol. 1997; 109:132-138
52. Robson MC. The role of growth factors in the healing of chronic wounds. Wound Repair Regen. 1997; 5:12-17
53. Falanga V, Eaglstei WH. The "trap" hypothesis of venous ulceration. Lancet. 1993; 341:1006-1008
54. Adair HM. Epidermal repair in venous ulcers. Br J Surg. 1997; 64:800-804
55. Andriessen MP, Van Bergen BH, Spruijt KI, et al.Epidermal proliferation is not impaired in chronic venous ulcers. Acta Derm Venereo. 1995;175:459-462
56. Clark RA, Ashcroft GS, Spencer MJ, et al.Re-epithelialization of normal human excisional wouds is associated with a switch from alpha v beta 5 to alpha v beta 6 integrins. Br J Dermatol. 1996; 135:46-51
57. Woodley DT. Reepithelialization. In Clark RAF (Ed): The Molecular and Cellular Biology of Wound Repair, Ed 2. New York Plenum Press. 1996; 339
58. Woodley DT, Bachmann PM, O'Keefe EJ. The role of matrix components in human keratinocyte reepithelialization. Prog Clin Biol Res. 1991; 65:129-140
59. O'Toole EA, Marinkovich MP, Hoeffler WK, et al.Laminin-5 inhibits human keratinocyte migration. Exp Cell Res. 1997; 233:330-339
60. Woodley DT, Bachmann PM, O'Keefe EJ. Laminin inhibits human keratinocyte migration. J Cell Physiol. 1988; 136:140-146
61. Larjava H. Expression of beta 1 integrins in normal human keratinocytes. Am J Med Sci. 1991; 301:63-68
62. Juhasz I, Murphy GF, Yan HC, et al. Regulation of extracellular matrix proteins and integrin cell substratum adhesion receptors on epithelium during cutaneous human wound healing in vivo. Am J Pathol. 1993; 143:1458-1469
63. Larjava H, Salo T, Haapasalmi K, et al. Expression of integrins and basement membrane components by wound keratinocytes. J Clin Invest. 1993; 92:1425-1435
64. Sheppard D. Epithelial integrins. Bioessays. 1996; 18:655-660
65. Sarret Y, Woodley DT, Grigsby K, et al. Human keratinocyte locomotion: The effet of selected cytokines. J Invest Dermatol. 1992; 98:12-16
66. Woodley DT, Chen JD, Kim JP, et al. Re-epithelialization: Human keratinocyte locomotion. Dermatol Clin. 1993; 11:641-646
67. Cowin AJ, Rayner TE, Cooter RD, et al. The expression of TGF-β and their receptors indicate reduced levels of TGF-β receptor type Ⅱ in chronic leg ulcers. Wound Repair and Regeneration. 1997; 5 (abstract): 109
68. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol. 1993; 101:64-68
69. Bullen EC, Longaker MT, Updike DL, et al. Tissue Inhibitor of
metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol. 1995; 104:236-240
70. Grinnell F, Ho CH, Wysock B. Degradation of fibronectin and vitronectin in chronic wound fluid: Analysis by cell blotting, immunoblotting, and cell adhesion assays. J Invest Dermatol. 1992; 98:410-416
71. Wysocki AB, Grinnell F. Fibronectin profiles in normal and chronic wound fluid. Lab Invest. 1990; 63:825-831
72. Grinnell F, Zhu M. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1 —proteinase inhibitor, and alpha2 macroglobulin, J Invest Dermatol. 1996; 106:335-341
73. Yager DR, Chen SM, Ward BS, et al. Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors. Wound Repair and Regeneration. 1997; 5:23-32
74. Rogers AA, Burnett S, Moore JC, et al. Involvement of proteolytic enzymes-plasminogen activators and matrix metalloproteinases in the pathophysiology of pressure ulcers. Wound Repair and Regeneration. 1995; 3:273-283
75. Argen GS, Taplin WC, Woessner JF, et al. Collagenases in wound healing: Effect of wound age and type. J Invest Dermatol.1992;99:709-14
76．李金清，陈绍宗，李学拥等．封闭负压引流技术对加速慢性创面愈合的机制．中国临床康复．2002；6：520-521
77. Yager DR, Xhang LY, Liang HX, et al.Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. J Invest Dermatol. 1996; 107:743-748
78. Nwomeh BC, Liang HX, Cohen IK, et al. MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. J surg Res. 1999; 81(2): 189-195
79. Grinnell F, Zhu M: Identification of neutrophil elastase as the proteinase in burn wound fluid responsible for degradation of fibronectin. J Invest Dermatol. 1994; 103:155-161
80. Rao CN, Ladin DA, Liu YY, et al. Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fibronectin from degradation by chronic wound fluid enzymes. J Invest Dermatol. 1995; 105:572-578
81. Edlich RF, Rogers W, Kasper G, et al. Studies in the management of the contaminated wound. I. Optimal time for closure of contaminated open wounds. Ⅱ. Comparison of resistance to infection of open and closed wounds during healing. Am J Surg. 1969; 117:323-329
82. Gilchrist B, Caroline R. The bacteriology of chronic venous ulcers treated with
occlusive hydrocolloid dressings. Br J Dermatol. 1989; 121:337
83. Krizek TK, Robson MC, Kho E. Bacterial growth and skin graft survival. Surgical Forum. 1967; 18:518-519
84. Kucan JO, Robson WC, Heggers JP, et al.Comparison of silver sulfadiazine, providone-iodine, and physiologic saline in the treatment of chronic pressure sores. J Am Geriatr Soc. 1981; 29:232-235
85. Rodeheaver G, Bellamy W, Kody M, et al.Bactericidal activity and toxicity of iodine-containing solutions in wound. Arch Surg. 1982; 117:181-186
86. Alvarez DM, Mertz PM, Eaglesten WH. Th effect of occlusive dressings on collagen synthesis and reepithelialization in superficial wounds. J Surg Res. 1983; 35:142-148
87. Brady SC, Snelling CPT, Chow G. Comparison of donor site dressings. Am Plast Surg. 1979; 5:238-243
88. Stephens FO, Dunphy JE, Hunt TK. Effect of delayed admition of corticosteroids on wound contraction. Ann Surg. 1971; 214-218
89. Camochan FMT, Abbott NC, Beek JS, et al. Can hyperbaric oxygen correct hypoxia induced by inflammation: Preliminary findings. In Schwartz J, Bakker D (Eds): Proceedings of the Swiss Symposium on Hyperbaric Medicine. Foundation for Hyperbaric Medicine, Baesel, 1989
90. Meltzer T, Myers B. The effect of hyperbaric oxygen on the bursting strength and rate of vascularization of skin wounds in the rat. Am Surg. 1986; 52:659-622
91. Sadegani K, Gottlieb SF, VanMeter K, et al.The effect of increased oxygen tension on healing surgical wounds. Undersea Biomed Res.1989; 16:42-47
92. Delfino M, Fabiani G, Divana E. Effects of hyperbaric oxygen in cryobiologic wounds. Arch Dermatol Res. 1990; 282:267-269
93. Jain KK. Hyperbaric oxygen therapy in infections. In Jain KK (ed): Textbook of Hyperbaric Medicine Hografe and Huber, Seattle, WA. 1996; 191-210
94. Roth RN, Weiss LD. Hyperbaric oxygen and wound healing. Clin Dermatol. 1994; 12:141-156
95. Lavan FB, Hunt TK. Oxygen and wound healing. Clin Plast Surg. 1990; 17:463-472,
96. Grim PS, Gottlieb LI, Boddie A, et al.Hyperbaric oxygen therapy: State-of-the-art/review. JAMA. 1990; 263:2216-2219
97. Monstrey SJ, Ramasastry SS, Mullick C, et al.Leg ulcers. In Cohen M (Ed): Mastery of Plastic and Reconstructive Surgery. Vol. 3, Little Brown and Co, Boston, MA. 1994; 1828-1838
98. Wattel F, Mathieu D, Coget IM, et al.Hyperbaric oxygen therapy in chronic vascular wound management. Angiology. 1990; 41:59-65
99. Knighton DR, Fiegel VD, Austin LL, et al. Classifications and treatment of
chronic nonhealing wounds. Ann Surg. 1986; 204:322-330
100. Steed DL.The Diabetic Ulcer Study Group. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg. 1995; 21:71-81
101. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with nonhealing diabetic ulcers: a phase Ⅲ randomized, placebo-controlled, double-blind study. Diabetes Care. 1998; 21:822-827
102. D'Hemecort PA, Smiell JM, Karim MR. Sodium carboxymethylcellulose aqueous-based gel vs. becaplermin gel in patients with nonhealing lower extremity diabetic ulcers. Wounds. 1998; 10:69-75
103. Brown G1, Nanney LB, Griffin J, et al. Enhancement of wound healing by topical treatment with epidermal growth factor. N Engl J Med. 1989; 321:76-79
104. Herndon DN, Barrow RE, Kunkel KR, et al. Effects of human growth hormone on donor-site healing in severely burned children. Ann Surg. 1990; 212:424-429
105. Robson MC. The role of growth factors in the healing of chronic wounds. Wound Repair and Regeneration. 1997; 5:12-17,
106. Davidson JM, Broadley KN, Quaglino D Jr. Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor—β 1 therapy. Wound Repair and Regeneration. 1997; 5:77-88
107. Hennessey PJ, Black CT, Andrassay RJ. Epidermal growth factor and insulin act synergistically during diabetic healing. Arch Surg. 1990; 125:926-929
108. Ramasastry SS, Weinzweig N. Free flap reconstruction of recalcitrant lower extremity ulcers in crest syndrome patients. Plast Surg Forum. 1997; 20:350
109. Ramasastry SS, Weinzweig N, Liang MD, et al.Limb salvage combining microvascular free tissue transfer and distal arterial revascularization in patients with extensive soft tissue loss. Plast surg Forum, 1997; 20:95-98
110. Argenta LC, Morykwas MJ. Vacuum-assisted Closure: a new method for wound control and treatment: Clinical experience. Ann Plast Surg.1997; 38: 563-576
111. Morykwas MJ, Argenta LC, Shelton. Brown EI, et al. Vacuum-assisted Closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997; 38: 553-562
112. Hartnett JM. Use of Vacuum-assisted wound closure in three chronic wounds. J wound Ostomy Continence Nurs. 1998; 25: 281-290
113. Bauer P, Schmidt G, Partecke BD. Possibilities of preliminary treatment of infected soft tissue defects by vacuum sealing and PVA foam. Handchir Mikrochir Plast Chir. 1998; 30: 20-23
114. Deva AK, Buckland GH, Fisher E, et al. Topical negative pressure in wound
management. Med J Aust. 2000; 173: 128-131
115. Meara JG, Guol, Smith JD, et al. Vacuum-assisted closure in the treatment of degloving injuries. Ann Plast Surg 1999; 42: 589-594
116. Baynham SA, Kohlman P, Katner HP. Treating stage Ⅳ pressure ulcers with negative pressure therapy: a case report. Ostomy woud Manage. 1999; 45: 28-37,34-35
117. Mooney JF 3rd, Argenta LC, Marks MW, et al. Treatment of soft tissue defects in pediatric patients using the VAC system. Clin Orthop 2000; 376:26-31
118. Fleischmann W, Strecker W, Bombell T: et al. Vacuum sealing as treatment of soft tissue damage in open fractures. Unfallchirurg 1993; 96: 488-492
119．黄雄飞，杜靖远，罗怀灿，等．封闭式负压吸引治疗开放性骨折合并软组织缺损．中华创伤杂志．1998；14：183-185
120．王彦峰，陶世明，陈务民，等．应用医用泡沫材料封闭负压引流治疗严重感染创面．中华实验外科杂志，1997；14：312-313
121. Mullner T, Mrkonjic L, Kwasny O, et al. The use of negative pressure to promote the healing of tissue defects: a clinical trial using the vacuum sealing technique. Br J Plast Surg 1997; 50: 194-199
122. Blackburn Ⅱ JH, Boeni L, Hall WW, et al. Negative-pressure dressings as a bolster for skin grafts. Ann Plast Surg 1998; 40: 453-457
123. Schneider AM, Morykwas MJ, Argenta LC. A new and reliable method of securing skin grafts to the difficult recipient bed. Plast Reconstr Surg 1998; 102:1195-1198
124．许龙顺．创面封闭负压引流技术促进创面愈合的实验与临床研究．博士学位论文，2001
125．李靖．封闭负压引流技术对创面微循环影响的实验研究．硕士学位论文．2001
126．李金清．封闭负压引流技术对人慢性创面中活性形式明胶酶和纤维连结蛋白的影响．硕士学位论文，2002
127. Inoue M, Kratz G. Haegerstrand A et al. Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization. J Invest Dermatol. 1995; 104: 479-83.
128. Wallace HJ, Stacey MC. Levels of TNF-α and soluble TNF receptors in chronic venous leg ulcers-correlations to healing status. J Invest Dermatol 1998; 110:292-296
129. Docherty AJ, Murphy G. Ann Rheum Dis, The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. 1990; 49: 469-479
130. Matrisian LM. Bioessays, The matrix-degrading metalloproteinases. Bioessays.
1992; 14: 455-463.
131. Salo H, Takino T, Okada Y et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994; 370: 61-65.
132. Goetzl EJ et al. Matrix metalloproteinases in immunity. J Immunol. 1996; 156: 1-4. Review.
133. Nwomeh BC, Liang HX, Diegelmann RF, et al. Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds. Wound Repair Regen. 1998; 6: 127-34.
134. Knauper V, Lopez-OtinC, Smith B, et al. Biochemical characterization of human collagenase-3. J Bio 1 Chem. 1996; 271:1544-1550
135. Hibbs Ms, Hasty KA, Seyer JM, et al. Biochemical and immunochemical characterization of the secreted forms of human neutrophil gelatinase. J Biol chem. 1985; 260:2493-2500
136. Bauer EA, Stricklin GP, Jeffery JJ, et al. Collagenase production by human skin fibroblasts. Biochem Biophys Res Commun. 1975; 64:232-240
137. Saarialho-Kere UK, Kovacs SO, Pentland AP, et al.Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest. 1993; 92:2858-2866
138. Vaalamo M, eckroth M, Puolakkainen P, et al.Patterns of matrix metalloproteinase and TIMP-1expression in chronic and normally healing cutaneous wounds. Br J Dermatol. 1996; 135:52-59
139. Ashcroft GS, Horan MA, Herrick SE, et al.Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans. Cell Tissue Res 1997; 290:581-591
140. Oikarinen A, Kylmaniemi M, Autio-Harmainen H, et al.Demonstration of 72-kDa forms of type IV collagenase in human skin: Variable expression in various blistering diseases, induction during re-epithelialization, and decrease by topical glucocorticoids. J Invest Dermatol. 1993; 101:205-210
141. Sato T, Makela M, Kylmaniemi M, et al.Expression of matrix metalloproteinase-2 and —9 during early human wound healing. Lab Invest. 1994; 70:176-182
142. Saarialho-Dere UK, Pentland AP, Birkedal-Hansen H, et al.Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest. 1994; 94:79-88
143. Agren MS. Gelatinase activity during wound healing. Br J Dermatol. 1994; 131:634-640
144. Saarialho-kere UK, Vaalamo M, Puolakkainen P, et al. Enhanced expression of matrilysin collagenase, and stromelysin-1 in gastrointestinal ulcers. Am J Pathol.
1996; 148:519-526
145. Okada A, Tomasetto C, Lutz Y, et al. Expression of metalloproteinases during rat skin wound healing: evidence that membrane type-1 matrix metalloproteinase is a stromal activator of pro-gelatinase A.J cell Biol. 1997; 137:67-77
146. Vaalamo M, Mattila L, Johanssn N, et al. Distinct population of stromal cells expresses MMP-13 and MMP-1 in chronic ulcers but not in normally healing wounds. J Invest Dermatol.1997; 109:96-101
147. Edwards DR, Beandry PP, Laing TD, et al. The roles of tissue inhibitors of metalloproteinases in tissue remodeling and cell growth. Int J of Obesity. 1996; 20 Suppl. 3: S9-S15
148. Woessner JF, Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FEBS Letts 1991; 5:2145-2154
149. Denhardt DT, Feng B, Edwards DR, et al. Tissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of expression and biological functions. Pharmac Ther 1993; 59:329-341
150. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64:327-336
151. Brinckerhoff CE. Regulation of metalloproteinase gene expression: implications for osteoarthritis. Crit Rev Euk Gen Exp 1992; 2:145-164
152. Armstrong PW, Moe GW, Howard RJ, et al. Structural remodeling in heart failure: gelatinase induction. Can J Cardiol 1994; 10:214-220
153. Milani S, Herbst H, Schuppan D, et al. Differential expression of matrix metalloproteinase-1 and —2 genes in normal and fibrotic human liver. Am J Pathol 1994; 144:528-537
154. Khokha R, Zimmer MJ, Graham CH, et al. Suppression of invasion by inducible expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in B16-F10 melanoma cells. J Natl Cancer Inst 1992; 84:1017-1023
155. Declerck YA, Perez N, Shimada H, et al. Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 1992; 52:701-708
156. Gomez DE, Alonso DF, Yoshij H, et al.Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions. Eur J Cell Biol. 1997; 74:111-122
157. Strongin AY, Collier I, Bannikov G, et al.Mechanism of cell surface activation of 72 kDa type IV collagenase: Isolation of the activated form of the membrane metalloproteinase. J Biol Chem. 1995; 270:5331-5338
158. Apte SS, Mattei MG, Olsen BR. Cloning of the cDNA encoding issue inhibitor of metalloproteinases (TIMP-3) and mapping of the TIMP-3 gene to chromosome 22. Genomics. 1994; 19:86-90
159. Uria JA, Ferrando AA, Velasco G, et al. Structure and expression in breast
tumors of human TIMP-3, a new member of the metalloproteinase inhibitor family. Cancer Res. 1994; 54:2091-2094
160. Airola K, Ahonen M, Johansson N, et al.Human TIMP-3 is expressed during fetal development, hair growth cycle and cancer progression. J Histochem Cytochem. 1998; 46:1-11
161. Vaalamo M, Karjalainen-Lindsberg M-L, Puolakkainen P, et al. Distinct expression profiles of stromelysin-2 (MMP-10), collagenase-3 (MMP-13), macrophage metalloelastase (MMP-12), and tissue inhibitor of metalloproteinases-3 (TIMP-3) in intestinal ulcerations. Am J Pathol. 1998; 152:1005-1014
162. Leco KJ, Khokha R, Pavloff N, et al. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues. J Biol Chem. 1994; 269:9352-9360
163. Apte SS, Olsen BR, Murphy G. The gene structure of tissue inhibitor of metalloproteinases (TIMP-3) and its inhibitory activity define the distinct TIMP gene family. J Biol Chem. 1995; 270:14313-14318
164. Greene J, Wang M, Lin YE, et al. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4.J Biol Chem. 1996; 271:30375-30380
165. Vaalamo M, Leivo T, Saarialho-kere U. Differential expression of tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4) in normal and aberrant wound healing. Hum Pathol. 1999; 30(7): 795-802
166. Howard EW, Bullen EC, Banda MJ. Preferertial inhibition of 72- and 92-kDa gelatinases by tissue inhibitor of metalloproteinases 2. J Biol Chem 1991; 266:13070-13075
167. Willenbrock F, Crabbe T, Slocombe PM, et al. The activity of the tissue inhibitors of metalloproteinases is regulated by C-terminal domain interactions: a kinetic analysis of the inhibition of gelatinase-A. Biochemistry 1993; 32:4330-4337
168. Staskus PW, Masiarz FR, Pallanck LJ, et al. The 21-kDa proteins is a transformation-sensitive metalloproteinase inhibitor of chicken fibroblasts. J Biol Chem 1991; 266:449-454
169. Yayon A, Klagsbrun M, Eskio Leder P, et al. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to yts high affinity receptor. Cell 1991; 64:841-848
170. Lopez-Casillas F, Wrana JL, Massagne J. Betaglycan presents ligand to the TGF-β signaling receptor. Cell 1993; 73:1435-1444
171. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, stucture and function. Biochemica et Biophysica Acta 2000;
1477:267-283
172. Bertaux B, Hornebeck W, Eisen AZ, et al. Growth stimulation of human keratinocytes by tissue inhibitor of metalloproteinases. J Invest Dermatol 1991; 97:670-685
173. Hayakawa T, Yamashita K, Uchijima E, et al. Growth-promoting activity of tissue inhibitor of metalloproteinases-1 (TIMP-1) for a wide range of cells. FEBS Letts 1992; 298:29-32
174. Khokha R, Waterhouse P, Yagel S, et al. Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells. Science 1989; 243:947-950
175. Williamson RA, Marsto FAO, Angal S, et al. Disulphide bond assignments in human tissue inhibitor of metalloproteinases (TIMP), Biochem J 1990; 268:267-274
176. O'Shea M, Willenbrock F, Williamson RA, et al. Site-directed mutations that alter the inhibitory activity of the tissue inhibitor of metalloproteinases-1: importance of the N-terminal region between cysteine 3 and cysteine 13. Biochemistry 1992; 31:10146-10152
177. Boden MK, Harber GJ, Birkedal-Hansen B, et al. Functional domains of human TIMP-1 (tissue inhibitor of metalloproteinases). J Biol Chem 1994; 269:18943-18952
178. Mauviel A. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem. 1993; 53: 288-95.
179. Delany AM, Brinckerhoff CE. Post-transcriptional regulation of collagenase and stromelysin gene expression by epidermal growth factor and dexamethasone in cultured human fibroblasts. J Cell Biochem. 1992; 50: 400-10.
180. Wolf C, Rouyer N, Lutz Y, et al. Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci U S A. 1993; 90: 1843-7
181. Bian JH, Sun Y. Transcriptional activation by P53 of the human type IV collagerase (Gelatinase A or matrix metalloproteinse 2) promoter. Molecular and Cellular Biology. 1997; 17:6330-6338
182. Madri JA, Basson MD. Extracellular matrix-cell interactions: dynamic modulators of cell, tissue and organism structure and function. Lab Invest. 1992; 66: 519-21.
183. Springman EB, Angleton EL, Birkedal-Hansen H, et al. Multiple modes of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active-site zinc complex in latency and a "cysteine switch" mechanism for activation. Proc Natl Acad Sci U S A. 1990; 87:364-8
184. Grignon DJ, Sakr W, Toth M, et al. High levels of tissue inhibitor of
metalloproteinase-2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. Cancer Res. 1996 1; 56: 1654-9.
185. Leco KJ, Khokha R, Pavioff N, et al. Tissue inhibitor of metalloproteinaes-3 (TIMP-3) is extracellular matrix-associated protein with a distinction pattern of expression in mouse cells and tissues. J Biol Chem 1994; 269:9352-9360
186. Campbell CE, Flenniken AM, Skup D, et al. Identification of a serum and phorbol ester-responsive element in the murine tisse inhibitor of metalloproteinase gene. J Biol Chem 1991; 266:7199-7206
187. Edwards DR, Rocheleau H, Sharma RR, et al. Involvement of AP1 and PEA3 binding sites in the regulation of murine tissue inhibitor of metalloproteinases (TIMP-1) transcription. Biochem Biophys Acta 1992; 1171:41-55
188. Leco KJ, Hayden LI. Sharma RR, et al. Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras-transformed murine fibroblasts. Gene 1992; 117:209-217
189. DeClerck YA, Dartll MI, Eeckhout Y, et al. Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2). Gene 1994; 139:185-191
190. Uchijima M, Sato H, Fujii M, et al. Tax proteins of human T-cell leukemia virus tpe 1 and 2 induce expression of the gene encoding erythroid potentiating activity (tissue inhibitor of metalloproteinases-1, TIMP-1). J Biol Chem 1994; 269:14526-14950
191. Ponton A, Coulomte B, Steyaert A, et al. Basal expression of the gene (TIMP) encoding the murine tissue inhibtor of metalloproteinases is medicated through AP1- and CCAAT-binding factors. Gene 1992; 116:187-194
192. Gaire M, Magbanul Z, McDonnell S, et al. Structure and expression of the human gene for the matrix metalloproteinase matrilysin. J Biol Chem 1994; 269:2032-2040
193. Nomura S, Hogan 3LM, Wills AJ, et al. Developmental expression of tissue inhibitor of metalloproteinase (TIMP) RNA. Development 1989; 105:575-583
194. Waterhouse P, Denhardt DT, Khokha R. Temporal expression of tissue inhibitors of metalloproteinases in mouse reproductive tissues during gestation. Mol Reprod Dev 1993; 35:219-226
195. Apte SS, Hayashi K. Seldi MF, et al. Gene encodng a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage and muscle and is located on mouse thromosome 10. Develop Dynam 1994; 200:177-179
196. Stricklin GP, Liying L, Jancic V et al. Localization of mRNAs representing collagenase and TIMP in sections of healing human burn wounds. Am J pathol. 1993; 143:1657-1666
197. Inoue M, Kratz G. Haegerstrand A, et al. Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization. J Invest Dermatol. 1995; 104: 479-83.
198. Weckroth M, Vaheri A, Lauharanta J, et al. Matrix metalloproteinases, gelatinase and collagenase in chronic leg ulcers. J Invest Dermatol 1996; 106:1119-1124
199. Howard EW, Bullen EC, Banda MJ: Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem 1991; 266:13064-13069
200. Kjeldsen L, Sengelov H, Lollike K, et al.Isolation and characterization gelatinase granules from human neutrophils. Blood. 1994; 83:1640-1649
201. Murphy G, Willenbrock F, Ward RV, et al. The C-terminal domain of 72-kDa gelatinase A is not required for catalysis, but essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases. Biochem J. 1992; 283:637-641
202. Barone EJ, Yager DR, Pozez AL, et al. Interleukin-12 and collagenase activity are elevated in chronic wounds. Plast Reconstr Surg 1998; 102:1023-1027
203. Heckmann M, Adelmann-Grill BC, Hein R, et al. Biphasic effects of interleukin-12 on dermal fibroblasts: enhancement of chemotactic responsiveness at low concentrations and of mRNA expression for collagenase at high concentrations. J Invest Dermatol. 1993; 100:780-788
204. Fini ME, Strissel KJ, Girarcl MT, et al. Interleukin-1 mediates collagenase synthesis stimulated by phorbol 12-myristate 13-acetate. J Biol chem. 1994; 269:11291-11295
205. Grinnell F, Zhu ME Parks WC. Collagenase-1 complexes α_2_macroglobulin in the acute and chronic wound environments. J Invest Dermatol. 1998; 110:771-776
206. Stricklin GP, Li LY, Nanney LB. Localization of mRNAs TIMP in healing porcine burn wounds. J Invest Dermatol. 1994; 103:352-358
207. Nwomeh BC, Liang HX, Cohen IK, et al. MMP-8 is the prcdominant collagenase in healing wounds and nonhealing ulcers. J of surg Res. 1999; 81:189-195
208. Bedi GS, Williams T. Purification and characterization of a collagen degrading protease from porphyromonas gingivalis. J Biol chem. 1994; 269:599-606
209. Cook H, Stephens P, Davies KJ, et al. Defective extracellular matrix reorganization by chronic wound fibroblasts is associated with alterations in TIMP-1, TIMP-2, and MMP-2 activity. J invest Dermatol 2000; 115:225-233
210. Soo C, Shaw ww, Zhang XL, et al. Differential expression of matrix metalloproteinases and their tissue-derived inhibitors in cutaneous wound repair.
Plast Reconstr Surg 2000; 105:638-647
211. Zeng GY, Millis AJT. Expression of 72-kDa gelatinase and TIMP-2 in early and late passage human fibroblasts. Exp cell Res 1994; 213:148-155
212. West MD, shay JW, Wright WE, et al. Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence. Exp Gerantol 1996; 31:175-193
213. Ashcroft GS, Herrick SE, Tarnuzzer RW, et al.Human aging impairs injury-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1 and —2 protein and mRNA. J Pathol. 1997; 183:169-176
214. Wick M, Burger C, Brusselbach S, et al.A novel member of human tissue inhibitor of metalloproteinases is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence. J Biol Chem. 1994; 269:18953-18960
215. Johansson N, saarialho-kere UK. Hypertrophic chendrocytes, periosteal cells and osteoblasts express Airolak, et al. Collagenase-3 (MMP-3) during fetal bone development. Dev Dyn 1997; 28:387-395
216. Kheradmand F,Werner E,Tremble P, et,al. Role of rac-1 and oxygen radicals in collagenase-1 expression induced by cell shape change. Science 1998; 280:898-902
217. Lovejoy B, Cleasby A, Hassell AM, et al. Sturcture of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science 1994; 263:375-377
218. Massova I, Kotra LP, Fridman R, et al. Matrix metalloproteinases: structures, evolution, and diversification. FASEB J 1998; 12:1075-1095
219. Parks WC. Matrix metalloproteinases in repair. Wound Repair Regen 1999; 7:423-432
220 石冰，陈绍宗，张萍等。封闭负压引流对人慢性创面中金属基质蛋白酶的影响。中国美容医学杂志。2003；12：10—13
221. Suomalainen K, Sorsa T, Golub LM, et al. Specificity of the anticollagenase action of tetracyclines: relevance to their anti-inflammatory potential. Antimicrobial Agents chemother 1992; 36:227-229
222. Sorsa T, Ding Y, salo T, et al. Effects of tetracyclines on neutrophl, gingival and salivary collagenases. A functional and western-blot assessment with special reference to their cellular sources in periodontal diseases. Ann NY Acad Sci 1994; 732:112-131
223. Lanhio A, Salo T, Ding Y, et al. In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and NSAID in acute reactive arthritis. Clin Exp Immunol 1994; 98:21-28
224. YU LP, Smith GN, Hasty KA, et al. Doxycycline inhibits type ⅩⅠ
collagenolytic activity of extracts from human osteoarthritic cartilage and of gelatinase J Rheumatol 1991; 18:1450-1452
225. Greenwald R, Golub LM, Lavietes B, et al. Tetracyclines inhibit human synovial collagenase in vivo and in vitro. J Rheumatol 1987; 14:28-32
226. Wallace HJ, Stacey MC. Levels of tumor necrosis factor-α (TNF-α) and soluble TNF receptors in chronic venous leg ulcers correlations to healing status. J Invest Dermatol 1998; 110:292-296
227. Trengove N, Langton S, Stacey M. Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers. Wound Rep Reg 1996; 4:234-239
228. Jue D, Sherry B, Luedke C, et al. Processing of newly synthesized cachectin/tumor necrosis factor in endo toxin-stimulated macrophages. Biochem.1990; 29:8371-8377
229. Schutze S, Scheurich P, Schluer C, et al. Tumor necrosis factor induced changes of gene expression in U 937 cells: Differentiation-dependent plasticity of the responsive state. J Immunol 1988; 140:3000-3005
230. Vilcek J, Palombella V, Henrikson-Destefano D, et, al. TNF soluble receptors circulate during experimental and clinical inflammation and can protect against excessive TNF-α in vitro and in vivo. Proc Natl Acad sci USA 1992; 89:4845-4849
231. Detmar M, Orfanos C. Tumor necrosis factor-alpha inhibits cell proliferation and induces class Ⅱ antigens and cell adhesion molecules in cultured normal human keratinocytes in vitro. Arch Dermatol Res 1990; 282:238-245
232. Mirshahi S, Soria J, Mirshahi M, et al.Expression of elastase and fibrin in venous leg ulcer biopsies: a pilot study of pentoxifylline vesus placebo. J cardiovasc Pharmacol 1995; 25(supp 1, 2): S101-S105
233. Higuchi M, Aggarwal B. Inhibition of ligand binding and antiproliferative effects of tumor necrosis factor and lymphotoxin by soluble forms of p60and p80 receptors. Res Commun 1992; 182:638-643
234. Scnderi P, Nez P, Duerr M, et al. Cathepsin-G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin. Cell Immunol 1991; 135:299-313
235．付小兵，顾小螟，孙同桂等，创面愈合组织三种生长相关因子表达及信号转导机制的实验研究。中华外科杂志，2001：39：714-717
236. Gu Xiaoman, Fu Xiaobing, Yang Yinhui, et al. Expression characteristics of c-fos, c-myc and bFGF in early burn tissue. Chinese Medical Journal 2001; 114:925-928
237. Cory A, Lekha P, Frank J, et al. Redox regulation of fos and Jun DNA-binding activiy in vitro. Science 1990; 249:1157-1161
238. Martin P, Nobes DC. An early molecular component of the wound healing
response in rat embryos: induction of c-fos protein in cells at the epidermal wound repair. Mech Der 1992; 38:209-216
239. Schonthal A, Herrlich P, Rahmsdorf HJ, et al. Requirment for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters. Cell.1998; 54:324-334
240. Tsuji M, Funahashi S, Takigawa M, et al. Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte. FEBS Lett. 1996; 381:222-226
241. Uria JA, Jimenez MG, Galbin M, et al. Differential effects of transforming growth factor-beta on the expression of collagenase-1 and collagenase-3 in human fibroblasts. J Biol chem 1998; 273:9769-9777
242. Crowe DL, Brown TN. Transcriptional inhibition of matrix metalloproteinase 9 (MMP-9) activities by a c-fos/estrogen receptor fusion protein is mediated by the proximal AP-1 site of the MMP-9 promoter and correlates with reduced tumor cell invasion. Neoplasia 1999; 1:368-72
243. Naruo S, Kanayama H, Aki M, et al. Gene expressions of type IV collagenase and tissue inhibitor of metalloproteinases (TIMPs) in human bladder cancers. Nippon Hinyokika Gakkai Zasshi 1993; 84:841-50
244. Fu Xiaobing, Jiang Lixian, Sun Tongzhu, et al. Expression of oncoproteins c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor. Chinese medical Journal 2001; 114:852-856
245. Cechowska-Pasko M, Palka J, Bankowski E. Decreased biosynthesis of glycosaminoglycans in the skin of rats with chronic diabetes mellitus. Exp Toxicol Patrol 1999; 51:239-243
246. Hehenberger K, Kratz G, Hansson A, et al. Fibroblasts derived from human chronic diabetic wounds has a decreased proliferation rate, which is recovered by the addition of heparin. J Dermatol sci 1998; 16:144-151
247. Galassi G, Brun P, Radice M, et al. In vitro reconstructed dermis implanted in human wounds: degradation studies of the HA-based supporting scaffold. Biomaterials 2000; 21:2183-2191
248. Hollander D, Stein M, BerndA, et al. Autologous keratinocytes cultured on benzyoester ulcers. J wound care 1999; 8:351-355
249. Depalma RL, Krummel TM, Durbam LA, et al.characterization and quantitation of wound matrix in fetal rabbit.Matrix.1989; 9:224-231
250. Knight.KR, Horne RS, Lepore, DA, et, al. Glycosaminoglycan composition of uninjured skin of scar tissue in fetal, newborn & adult sheep. Res Exp Med. 1994; 194:119-127
251. Longaker MT, Chiu ES, Adzick NS, et, al. Studies in fetal wound healing, V:
A prolonged presence of HA characterizes fetal wound fluid. Annals of surgery 1991; 213:292-296
252．石冰，柳大烈，马世英等．透明质酸含量在兔正常皮肤及皮肤创伤愈合过程的变化．中华医学美容杂志 1999；5：189-193
253. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998; 176(supp12A): 26s-38s
254．黄金井。真皮提取物对成纤维细胞的生长抑制作用的研究．中华整形烧伤外科杂志 1995；11：137-139
2. Kirsner RS, Eaglstein WH. The wound healing process. Dermatol Clin. 1993; 11:629-640
3. Fajardo LF, Berthrong M. Radiation injury in Surgical pathology Ⅲ: Salivary glands, pancreas and skin. Am J Surg Pathol. 1981; 5:279-296
4. Hunt TK, Niniikoski J, Zederfeldt BH, et al. Oxygen in wound healing enhancement: Cellular effects of oxygen. In Davis JC, Hunt TK (Eds): Hyperbaric Oxygen Therapy. Kensington, Maryland, Undersea Medical Society, 1977; 111-122
5. Niniikkoski J. Oxygen and wound healing. Clin Plast Surg. 1977; 4:361-374
6. Storch TG, Talley GD. Oxygen concentration regulates the proliferative response of tumor fibroblasts to serum and growth factors. Exp Cell Res. 1988; 175:317-325
7. Ramasastry SS. Chronic problem wounds. Clin in Plast Surg. 1998; 25(3): 367-396
8. Robson MC. Wound infection: a failure of wound healing used by an imbalance of bacteria. Surg Clin North Am. 1997; 77:650
9. Tobin GR. Wound repair: biologic foundations and clinical considerations. In: Richardson JD, Polk HC Jr, Flint LM Jr (eds). Inma: Clinical Care and pathophysiology. Chicago, IL: earbook local Publishers 1987; 213-26
10. Clore JN, Cohen IK, Diegelmann RF. Quantitation of collagen types Ⅲ and Ⅰ during wound healing in rat skin. Proc Soc Exp Bilo Med. 1979; 161:337-340
11. Gay S, Vijanto J, Raekallio J, et al.Collagen types in early phases of wound healing in children. Acta Chir Scand. 1978; 144:205-211
12. Madden JW, Peacock EE. Studies on the biology of collagen during wound healing: Rate of collagen synthesis and deposition in cutaneous wounds of the rat. Surgery 1968; 64:288-294
13. Clark RA. Cutaneous tissue repair: Basic biologic considerations. J Am Acad Dermatol 1985; 13:701-725
14. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998; 176(Suppl 2A): 26S-38S
15. Nwomeh BC, Yager DR, Cohen IK. Physiology of the chronic wound Clinics in Plastic surgery. 1998; 25: 341-356
16. Stadelmann WK, Digenis AG, Tobin GR. Impediments to wound healing. Am J Surg. 1998; 176(Supple 2A): 39S-47S
17. Hunt TK, Zederfeldt BH, Goldstick TK, et al.Tissue oxygen tension during controlled hemorrhage. Surgical Forum. 1967; 18:3-4
18. Hunt TK, Pai MP. The effect of varying ambient oxygen tension on wound metabolism and collagen synthesis. Surg Gynecol Obstet. 1972; 135:561-566
19. Niniikkoski J. Effect of oxygen supply on wound healing and formation of granulation tissue. Acta Physiol Scand. 1969; 3341 (suppl): 71-72
20. Stephens FO, Hunt TK. Effect of changes in impaired oxygen and carbon dioxide tensions on wound tensile strength: An experimental study. Ann Surg. 1971; 173:515-519
21. Hammarlund C, Sundberg T. Hyperbaric oxygen reduced size of chronic leg ulcers: A randomized double-blind study. Plast Reconstr Surg. 1994; 93:829-833
22. Hohn DC, Hunt TK. Oxidative metabolism and antimicrobial activity of rabbit phagocyte cells from wounds and from peripheral blood. Surgical Forum. 1975; 26:85-87
23. Hunt TK, Linsey M, Arislis G, et al.The effect of ambient oxygen tension on wound infection. Ann Surg. 1975; 181:35-39
24. Wagner VH, Keagy AA, Kottb MM, et al.Noninvasive determination of healing of major lower extremity amputations: The combined role of clinical Judgement. J Vasc Surg. 1988; 8:703-710
25. Sheffield PJ: Tissue oxygen measurement with respect to soft tissue wound healing with normobaric and hyperbaric oxygen. Hyperbaric Oxygen Rev. 1955; 6:18-46
26. Falanga V, Grinnell F, Gilchrest B, et al.Experimental approaches to chronic wounds. Wound Repair and Regeneration. 1995; 3: 132-140
27. Falanga V, Kirsner RS. Low oxygen stimulates proliferation of fibroblasts seeded as single cells. J Cell Physiol. 1993; 154:506-510,
28. Knighton DR, Hunt TK, Scheuenstuhl H, et al.Oxygen tension regulates the expression of angiogenesis factor by macrophages. Science. 1983; 221:1283-1285
29. Falanga V, Qian SW, Danielporu D, et al.Hypoxia upregulates the synthesis of TGF-beta 1 by human dermal fibroblasts. J Invest Dermatol. 1992; 97:634-637
30. Kourembanas S, Harman RL, Faller DV. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J Clin Invest. 1990; 86:670-674
31. Jorgensen LN, Kallehave F, Karlsmark T, et al.Reduced collagen accumulation after major surgery. Br J Surg. 1996; 83:1591-1594
32. Hueghan C, Grisils G, Hunt TK. The effect of anemia on wound healing. Ann Surg. 1974; 179:163-167
33. Stenberg BD, Phillips LG, Hodanson JA, et al. Effect of fibroblast growth factor
on the inhibition of contraction causes bacteria. J Surg Res. 1991; 50:47-50
34. Hayward P, Hokanson J, Heggers J, et al. Fibroblast grow factor reverses the bacterial retardation of wound contraction. Ann Surg. 1992; 163:288-293
35. Robson MC, Stenberg BD, Heggers JD. Wound healing alterations caused by bacteria. Clin Plast Surg. 1990; 3:485-492
36. Robson MC.Infection in the surgical patients: an imbalance the normal equilibrium. Clin Plast Surg. 1979; 6:493-503
37. Robson MC, Krizek TK, Heggers JP. Biology of surgical infection. Medical Publishers, 1973:1-62
38. Krizek TK, Robson MC, Kho E. Bacterial growth and skin survival. Surg Forum. 1967; 18:518-519
39. Thomson PD, Smith-DJ J. What is infection? Am J Surg. 1994; 167 (suppl): 7-10
40. Eriksson G, Eklund AE, Kallings LO. The clinical significance of bacterial growth in venous leg ulcers. Scand J Infect Dis. 1984; 6:175-180
41. Van RL, Brown D, Friedman S, et al.Multicenter clinical evaluation of a hydrocolloid dressing for leg ulcers. 1985; 35:173-176
42. Friedman SJ, Su WP. Management of leg ulcers with hydrocolloid occlusive dressing. Arch Dermatol. 1984; 120:1329-1336
43. Gilchrist B, Reed C. The bacteriology of chronic venous ulcers treated with occlusive hydrocolloid dressings. Br J Dermatol. 1989; 121:337-344
44. Steed DL.The Diabetic Ulcer Study Group. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg. 1995; 21:81
45. Greenhalgh DG. The role of growth factors in wound healing. J Trauma. 1996; 41: 159-167
46. Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg. 1993; 165:729-737
47. Bennett NT, Schultz GS. Growth factors and wound healing: part Ⅱ. Role in normal and chronic wound healing. Am J Surg. 1993; 166:74-81
48. Katz MH, Alvarez AF, Kirsner RS, et al.Human wound fluid from acute wounds stimulates fibroblast and endothelial cell growth. J Am Acad Dermatol. 1991; 25:1054-1058
49. Cooper DM, Yu EZ, Hennessey P, et al.Determination of endogenous cytokines in chronic wounds. Ann Surg. 1994; 219:688-691
50. Schmid P, Cox DA, Bilbe G, et al. TGF-βs and TGF-β type Ⅱ receptor in human epidermis: Differential expression in acute and chronic skin wounds. J Patrol. 1993; 171:191-197
51. Beer HD, Longaker MT, Erner S. Reduced expression of PDGF and PDGF
receptors during impaired wound healing. J Invest Dermatol. 1997; 109:132-138
52. Robson MC. The role of growth factors in the healing of chronic wounds. Wound Repair Regen. 1997; 5:12-17
53. Falanga V, Eaglstei WH. The "trap" hypothesis of venous ulceration. Lancet. 1993; 341:1006-1008
54. Adair HM. Epidermal repair in venous ulcers. Br J Surg. 1997; 64:800-804
55. Andriessen MP, Van Bergen BH, Spruijt KI, et al.Epidermal proliferation is not impaired in chronic venous ulcers. Acta Derm Venereo. 1995;175:459-462
56. Clark RA, Ashcroft GS, Spencer MJ, et al.Re-epithelialization of normal human excisional wouds is associated with a switch from alpha v beta 5 to alpha v beta 6 integrins. Br J Dermatol. 1996; 135:46-51
57. Woodley DT. Reepithelialization. In Clark RAF (Ed): The Molecular and Cellular Biology of Wound Repair, Ed 2. New York Plenum Press. 1996; 339
58. Woodley DT, Bachmann PM, O'Keefe EJ. The role of matrix components in human keratinocyte reepithelialization. Prog Clin Biol Res. 1991; 65:129-140
59. O'Toole EA, Marinkovich MP, Hoeffler WK, et al.Laminin-5 inhibits human keratinocyte migration. Exp Cell Res. 1997; 233:330-339
60. Woodley DT, Bachmann PM, O'Keefe EJ. Laminin inhibits human keratinocyte migration. J Cell Physiol. 1988; 136:140-146
61. Larjava H. Expression of beta 1 integrins in normal human keratinocytes. Am J Med Sci. 1991; 301:63-68
62. Juhasz I, Murphy GF, Yan HC, et al. Regulation of extracellular matrix proteins and integrin cell substratum adhesion receptors on epithelium during cutaneous human wound healing in vivo. Am J Pathol. 1993; 143:1458-1469
63. Larjava H, Salo T, Haapasalmi K, et al. Expression of integrins and basement membrane components by wound keratinocytes. J Clin Invest. 1993; 92:1425-1435
64. Sheppard D. Epithelial integrins. Bioessays. 1996; 18:655-660
65. Sarret Y, Woodley DT, Grigsby K, et al. Human keratinocyte locomotion: The effet of selected cytokines. J Invest Dermatol. 1992; 98:12-16
66. Woodley DT, Chen JD, Kim JP, et al. Re-epithelialization: Human keratinocyte locomotion. Dermatol Clin. 1993; 11:641-646
67. Cowin AJ, Rayner TE, Cooter RD, et al. The expression of TGF-β and their receptors indicate reduced levels of TGF-β receptor type Ⅱ in chronic leg ulcers. Wound Repair and Regeneration. 1997; 5 (abstract): 109
68. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol. 1993; 101:64-68
69. Bullen EC, Longaker MT, Updike DL, et al. Tissue Inhibitor of
metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds. J Invest Dermatol. 1995; 104:236-240
70. Grinnell F, Ho CH, Wysock B. Degradation of fibronectin and vitronectin in chronic wound fluid: Analysis by cell blotting, immunoblotting, and cell adhesion assays. J Invest Dermatol. 1992; 98:410-416
71. Wysocki AB, Grinnell F. Fibronectin profiles in normal and chronic wound fluid. Lab Invest. 1990; 63:825-831
72. Grinnell F, Zhu M. Fibronectin degradation in chronic wounds depends on the relative levels of elastase, alpha1 —proteinase inhibitor, and alpha2 macroglobulin, J Invest Dermatol. 1996; 106:335-341
73. Yager DR, Chen SM, Ward BS, et al. Ability of chronic wound fluids to degrade peptide growth factors is associated with increased levels of elastase activity and diminished levels of proteinase inhibitors. Wound Repair and Regeneration. 1997; 5:23-32
74. Rogers AA, Burnett S, Moore JC, et al. Involvement of proteolytic enzymes-plasminogen activators and matrix metalloproteinases in the pathophysiology of pressure ulcers. Wound Repair and Regeneration. 1995; 3:273-283
75. Argen GS, Taplin WC, Woessner JF, et al. Collagenases in wound healing: Effect of wound age and type. J Invest Dermatol.1992;99:709-14
76．李金清，陈绍宗，李学拥等．封闭负压引流技术对加速慢性创面愈合的机制．中国临床康复．2002；6：520-521
77. Yager DR, Xhang LY, Liang HX, et al.Wound fluids from human pressure ulcers contain elevated matrix metalloproteinase levels and activity compared to surgical wound fluids. J Invest Dermatol. 1996; 107:743-748
78. Nwomeh BC, Liang HX, Cohen IK, et al. MMP-8 is the predominant collagenase in healing wounds and nonhealing ulcers. J surg Res. 1999; 81(2): 189-195
79. Grinnell F, Zhu M: Identification of neutrophil elastase as the proteinase in burn wound fluid responsible for degradation of fibronectin. J Invest Dermatol. 1994; 103:155-161
80. Rao CN, Ladin DA, Liu YY, et al. Alpha 1-antitrypsin is degraded and non-functional in chronic wounds but intact and functional in acute wounds: the inhibitor protects fibronectin from degradation by chronic wound fluid enzymes. J Invest Dermatol. 1995; 105:572-578
81. Edlich RF, Rogers W, Kasper G, et al. Studies in the management of the contaminated wound. I. Optimal time for closure of contaminated open wounds. Ⅱ. Comparison of resistance to infection of open and closed wounds during healing. Am J Surg. 1969; 117:323-329
82. Gilchrist B, Caroline R. The bacteriology of chronic venous ulcers treated with
occlusive hydrocolloid dressings. Br J Dermatol. 1989; 121:337
83. Krizek TK, Robson MC, Kho E. Bacterial growth and skin graft survival. Surgical Forum. 1967; 18:518-519
84. Kucan JO, Robson WC, Heggers JP, et al.Comparison of silver sulfadiazine, providone-iodine, and physiologic saline in the treatment of chronic pressure sores. J Am Geriatr Soc. 1981; 29:232-235
85. Rodeheaver G, Bellamy W, Kody M, et al.Bactericidal activity and toxicity of iodine-containing solutions in wound. Arch Surg. 1982; 117:181-186
86. Alvarez DM, Mertz PM, Eaglesten WH. Th effect of occlusive dressings on collagen synthesis and reepithelialization in superficial wounds. J Surg Res. 1983; 35:142-148
87. Brady SC, Snelling CPT, Chow G. Comparison of donor site dressings. Am Plast Surg. 1979; 5:238-243
88. Stephens FO, Dunphy JE, Hunt TK. Effect of delayed admition of corticosteroids on wound contraction. Ann Surg. 1971; 214-218
89. Camochan FMT, Abbott NC, Beek JS, et al. Can hyperbaric oxygen correct hypoxia induced by inflammation: Preliminary findings. In Schwartz J, Bakker D (Eds): Proceedings of the Swiss Symposium on Hyperbaric Medicine. Foundation for Hyperbaric Medicine, Baesel, 1989
90. Meltzer T, Myers B. The effect of hyperbaric oxygen on the bursting strength and rate of vascularization of skin wounds in the rat. Am Surg. 1986; 52:659-622
91. Sadegani K, Gottlieb SF, VanMeter K, et al.The effect of increased oxygen tension on healing surgical wounds. Undersea Biomed Res.1989; 16:42-47
92. Delfino M, Fabiani G, Divana E. Effects of hyperbaric oxygen in cryobiologic wounds. Arch Dermatol Res. 1990; 282:267-269
93. Jain KK. Hyperbaric oxygen therapy in infections. In Jain KK (ed): Textbook of Hyperbaric Medicine Hografe and Huber, Seattle, WA. 1996; 191-210
94. Roth RN, Weiss LD. Hyperbaric oxygen and wound healing. Clin Dermatol. 1994; 12:141-156
95. Lavan FB, Hunt TK. Oxygen and wound healing. Clin Plast Surg. 1990; 17:463-472,
96. Grim PS, Gottlieb LI, Boddie A, et al.Hyperbaric oxygen therapy: State-of-the-art/review. JAMA. 1990; 263:2216-2219
97. Monstrey SJ, Ramasastry SS, Mullick C, et al.Leg ulcers. In Cohen M (Ed): Mastery of Plastic and Reconstructive Surgery. Vol. 3, Little Brown and Co, Boston, MA. 1994; 1828-1838
98. Wattel F, Mathieu D, Coget IM, et al.Hyperbaric oxygen therapy in chronic vascular wound management. Angiology. 1990; 41:59-65
99. Knighton DR, Fiegel VD, Austin LL, et al. Classifications and treatment of
chronic nonhealing wounds. Ann Surg. 1986; 204:322-330
100. Steed DL.The Diabetic Ulcer Study Group. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity diabetic ulcers. J Vasc Surg. 1995; 21:71-81
101. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with nonhealing diabetic ulcers: a phase Ⅲ randomized, placebo-controlled, double-blind study. Diabetes Care. 1998; 21:822-827
102. D'Hemecort PA, Smiell JM, Karim MR. Sodium carboxymethylcellulose aqueous-based gel vs. becaplermin gel in patients with nonhealing lower extremity diabetic ulcers. Wounds. 1998; 10:69-75
103. Brown G1, Nanney LB, Griffin J, et al. Enhancement of wound healing by topical treatment with epidermal growth factor. N Engl J Med. 1989; 321:76-79
104. Herndon DN, Barrow RE, Kunkel KR, et al. Effects of human growth hormone on donor-site healing in severely burned children. Ann Surg. 1990; 212:424-429
105. Robson MC. The role of growth factors in the healing of chronic wounds. Wound Repair and Regeneration. 1997; 5:12-17,
106. Davidson JM, Broadley KN, Quaglino D Jr. Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor—β 1 therapy. Wound Repair and Regeneration. 1997; 5:77-88
107. Hennessey PJ, Black CT, Andrassay RJ. Epidermal growth factor and insulin act synergistically during diabetic healing. Arch Surg. 1990; 125:926-929
108. Ramasastry SS, Weinzweig N. Free flap reconstruction of recalcitrant lower extremity ulcers in crest syndrome patients. Plast Surg Forum. 1997; 20:350
109. Ramasastry SS, Weinzweig N, Liang MD, et al.Limb salvage combining microvascular free tissue transfer and distal arterial revascularization in patients with extensive soft tissue loss. Plast surg Forum, 1997; 20:95-98
110. Argenta LC, Morykwas MJ. Vacuum-assisted Closure: a new method for wound control and treatment: Clinical experience. Ann Plast Surg.1997; 38: 563-576
111. Morykwas MJ, Argenta LC, Shelton. Brown EI, et al. Vacuum-assisted Closure: a new method for wound control and treatment: animal studies and basic foundation. Ann Plast Surg. 1997; 38: 553-562
112. Hartnett JM. Use of Vacuum-assisted wound closure in three chronic wounds. J wound Ostomy Continence Nurs. 1998; 25: 281-290
113. Bauer P, Schmidt G, Partecke BD. Possibilities of preliminary treatment of infected soft tissue defects by vacuum sealing and PVA foam. Handchir Mikrochir Plast Chir. 1998; 30: 20-23
114. Deva AK, Buckland GH, Fisher E, et al. Topical negative pressure in wound
management. Med J Aust. 2000; 173: 128-131
115. Meara JG, Guol, Smith JD, et al. Vacuum-assisted closure in the treatment of degloving injuries. Ann Plast Surg 1999; 42: 589-594
116. Baynham SA, Kohlman P, Katner HP. Treating stage Ⅳ pressure ulcers with negative pressure therapy: a case report. Ostomy woud Manage. 1999; 45: 28-37,34-35
117. Mooney JF 3rd, Argenta LC, Marks MW, et al. Treatment of soft tissue defects in pediatric patients using the VAC system. Clin Orthop 2000; 376:26-31
118. Fleischmann W, Strecker W, Bombell T: et al. Vacuum sealing as treatment of soft tissue damage in open fractures. Unfallchirurg 1993; 96: 488-492
119．黄雄飞，杜靖远，罗怀灿，等．封闭式负压吸引治疗开放性骨折合并软组织缺损．中华创伤杂志．1998；14：183-185
120．王彦峰，陶世明，陈务民，等．应用医用泡沫材料封闭负压引流治疗严重感染创面．中华实验外科杂志，1997；14：312-313
121. Mullner T, Mrkonjic L, Kwasny O, et al. The use of negative pressure to promote the healing of tissue defects: a clinical trial using the vacuum sealing technique. Br J Plast Surg 1997; 50: 194-199
122. Blackburn Ⅱ JH, Boeni L, Hall WW, et al. Negative-pressure dressings as a bolster for skin grafts. Ann Plast Surg 1998; 40: 453-457
123. Schneider AM, Morykwas MJ, Argenta LC. A new and reliable method of securing skin grafts to the difficult recipient bed. Plast Reconstr Surg 1998; 102:1195-1198
124．许龙顺．创面封闭负压引流技术促进创面愈合的实验与临床研究．博士学位论文，2001
125．李靖．封闭负压引流技术对创面微循环影响的实验研究．硕士学位论文．2001
126．李金清．封闭负压引流技术对人慢性创面中活性形式明胶酶和纤维连结蛋白的影响．硕士学位论文，2002
127. Inoue M, Kratz G. Haegerstrand A et al. Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization. J Invest Dermatol. 1995; 104: 479-83.
128. Wallace HJ, Stacey MC. Levels of TNF-α and soluble TNF receptors in chronic venous leg ulcers-correlations to healing status. J Invest Dermatol 1998; 110:292-296
129. Docherty AJ, Murphy G. Ann Rheum Dis, The tissue metalloproteinase family and the inhibitor TIMP: a study using cDNAs and recombinant proteins. 1990; 49: 469-479
130. Matrisian LM. Bioessays, The matrix-degrading metalloproteinases. Bioessays.
1992; 14: 455-463.
131. Salo H, Takino T, Okada Y et al. A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 1994; 370: 61-65.
132. Goetzl EJ et al. Matrix metalloproteinases in immunity. J Immunol. 1996; 156: 1-4. Review.
133. Nwomeh BC, Liang HX, Diegelmann RF, et al. Dynamics of the matrix metalloproteinases MMP-1 and MMP-8 in acute open human dermal wounds. Wound Repair Regen. 1998; 6: 127-34.
134. Knauper V, Lopez-OtinC, Smith B, et al. Biochemical characterization of human collagenase-3. J Bio 1 Chem. 1996; 271:1544-1550
135. Hibbs Ms, Hasty KA, Seyer JM, et al. Biochemical and immunochemical characterization of the secreted forms of human neutrophil gelatinase. J Biol chem. 1985; 260:2493-2500
136. Bauer EA, Stricklin GP, Jeffery JJ, et al. Collagenase production by human skin fibroblasts. Biochem Biophys Res Commun. 1975; 64:232-240
137. Saarialho-Kere UK, Kovacs SO, Pentland AP, et al.Cell-matrix interactions modulate interstitial collagenase expression by human keratinocytes actively involved in wound healing. J Clin Invest. 1993; 92:2858-2866
138. Vaalamo M, eckroth M, Puolakkainen P, et al.Patterns of matrix metalloproteinase and TIMP-1expression in chronic and normally healing cutaneous wounds. Br J Dermatol. 1996; 135:52-59
139. Ashcroft GS, Horan MA, Herrick SE, et al.Age-related differences in the temporal and spatial regulation of matrix metalloproteinases (MMPs) in normal skin and acute cutaneous wounds of healthy humans. Cell Tissue Res 1997; 290:581-591
140. Oikarinen A, Kylmaniemi M, Autio-Harmainen H, et al.Demonstration of 72-kDa forms of type IV collagenase in human skin: Variable expression in various blistering diseases, induction during re-epithelialization, and decrease by topical glucocorticoids. J Invest Dermatol. 1993; 101:205-210
141. Sato T, Makela M, Kylmaniemi M, et al.Expression of matrix metalloproteinase-2 and —9 during early human wound healing. Lab Invest. 1994; 70:176-182
142. Saarialho-Dere UK, Pentland AP, Birkedal-Hansen H, et al.Distinct populations of basal keratinocytes express stromelysin-1 and stromelysin-2 in chronic wounds. J Clin Invest. 1994; 94:79-88
143. Agren MS. Gelatinase activity during wound healing. Br J Dermatol. 1994; 131:634-640
144. Saarialho-kere UK, Vaalamo M, Puolakkainen P, et al. Enhanced expression of matrilysin collagenase, and stromelysin-1 in gastrointestinal ulcers. Am J Pathol.
1996; 148:519-526
145. Okada A, Tomasetto C, Lutz Y, et al. Expression of metalloproteinases during rat skin wound healing: evidence that membrane type-1 matrix metalloproteinase is a stromal activator of pro-gelatinase A.J cell Biol. 1997; 137:67-77
146. Vaalamo M, Mattila L, Johanssn N, et al. Distinct population of stromal cells expresses MMP-13 and MMP-1 in chronic ulcers but not in normally healing wounds. J Invest Dermatol.1997; 109:96-101
147. Edwards DR, Beandry PP, Laing TD, et al. The roles of tissue inhibitors of metalloproteinases in tissue remodeling and cell growth. Int J of Obesity. 1996; 20 Suppl. 3: S9-S15
148. Woessner JF, Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FEBS Letts 1991; 5:2145-2154
149. Denhardt DT, Feng B, Edwards DR, et al. Tissue inhibitor of metalloproteinases (TIMP, aka EPA): structure, control of expression and biological functions. Pharmac Ther 1993; 59:329-341
150. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64:327-336
151. Brinckerhoff CE. Regulation of metalloproteinase gene expression: implications for osteoarthritis. Crit Rev Euk Gen Exp 1992; 2:145-164
152. Armstrong PW, Moe GW, Howard RJ, et al. Structural remodeling in heart failure: gelatinase induction. Can J Cardiol 1994; 10:214-220
153. Milani S, Herbst H, Schuppan D, et al. Differential expression of matrix metalloproteinase-1 and —2 genes in normal and fibrotic human liver. Am J Pathol 1994; 144:528-537
154. Khokha R, Zimmer MJ, Graham CH, et al. Suppression of invasion by inducible expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) in B16-F10 melanoma cells. J Natl Cancer Inst 1992; 84:1017-1023
155. Declerck YA, Perez N, Shimada H, et al. Inhibition of invasion and metastasis in cells transfected with an inhibitor of metalloproteinases. Cancer Res 1992; 52:701-708
156. Gomez DE, Alonso DF, Yoshij H, et al.Tissue inhibitors of metalloproteinases: Structure, regulation and biological functions. Eur J Cell Biol. 1997; 74:111-122
157. Strongin AY, Collier I, Bannikov G, et al.Mechanism of cell surface activation of 72 kDa type IV collagenase: Isolation of the activated form of the membrane metalloproteinase. J Biol Chem. 1995; 270:5331-5338
158. Apte SS, Mattei MG, Olsen BR. Cloning of the cDNA encoding issue inhibitor of metalloproteinases (TIMP-3) and mapping of the TIMP-3 gene to chromosome 22. Genomics. 1994; 19:86-90
159. Uria JA, Ferrando AA, Velasco G, et al. Structure and expression in breast
tumors of human TIMP-3, a new member of the metalloproteinase inhibitor family. Cancer Res. 1994; 54:2091-2094
160. Airola K, Ahonen M, Johansson N, et al.Human TIMP-3 is expressed during fetal development, hair growth cycle and cancer progression. J Histochem Cytochem. 1998; 46:1-11
161. Vaalamo M, Karjalainen-Lindsberg M-L, Puolakkainen P, et al. Distinct expression profiles of stromelysin-2 (MMP-10), collagenase-3 (MMP-13), macrophage metalloelastase (MMP-12), and tissue inhibitor of metalloproteinases-3 (TIMP-3) in intestinal ulcerations. Am J Pathol. 1998; 152:1005-1014
162. Leco KJ, Khokha R, Pavloff N, et al. Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues. J Biol Chem. 1994; 269:9352-9360
163. Apte SS, Olsen BR, Murphy G. The gene structure of tissue inhibitor of metalloproteinases (TIMP-3) and its inhibitory activity define the distinct TIMP gene family. J Biol Chem. 1995; 270:14313-14318
164. Greene J, Wang M, Lin YE, et al. Molecular cloning and characterization of human tissue inhibitor of metalloproteinase 4.J Biol Chem. 1996; 271:30375-30380
165. Vaalamo M, Leivo T, Saarialho-kere U. Differential expression of tissue inhibitors of metalloproteinases (TIMP-1, 2, 3 and 4) in normal and aberrant wound healing. Hum Pathol. 1999; 30(7): 795-802
166. Howard EW, Bullen EC, Banda MJ. Preferertial inhibition of 72- and 92-kDa gelatinases by tissue inhibitor of metalloproteinases 2. J Biol Chem 1991; 266:13070-13075
167. Willenbrock F, Crabbe T, Slocombe PM, et al. The activity of the tissue inhibitors of metalloproteinases is regulated by C-terminal domain interactions: a kinetic analysis of the inhibition of gelatinase-A. Biochemistry 1993; 32:4330-4337
168. Staskus PW, Masiarz FR, Pallanck LJ, et al. The 21-kDa proteins is a transformation-sensitive metalloproteinase inhibitor of chicken fibroblasts. J Biol Chem 1991; 266:449-454
169. Yayon A, Klagsbrun M, Eskio Leder P, et al. Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to yts high affinity receptor. Cell 1991; 64:841-848
170. Lopez-Casillas F, Wrana JL, Massagne J. Betaglycan presents ligand to the TGF-β signaling receptor. Cell 1993; 73:1435-1444
171. Brew K, Dinakarpandian D, Nagase H. Tissue inhibitors of metalloproteinases: evolution, stucture and function. Biochemica et Biophysica Acta 2000;
1477:267-283
172. Bertaux B, Hornebeck W, Eisen AZ, et al. Growth stimulation of human keratinocytes by tissue inhibitor of metalloproteinases. J Invest Dermatol 1991; 97:670-685
173. Hayakawa T, Yamashita K, Uchijima E, et al. Growth-promoting activity of tissue inhibitor of metalloproteinases-1 (TIMP-1) for a wide range of cells. FEBS Letts 1992; 298:29-32
174. Khokha R, Waterhouse P, Yagel S, et al. Antisense RNA-induced reduction in murine TIMP levels confers oncogenicity on Swiss 3T3 cells. Science 1989; 243:947-950
175. Williamson RA, Marsto FAO, Angal S, et al. Disulphide bond assignments in human tissue inhibitor of metalloproteinases (TIMP), Biochem J 1990; 268:267-274
176. O'Shea M, Willenbrock F, Williamson RA, et al. Site-directed mutations that alter the inhibitory activity of the tissue inhibitor of metalloproteinases-1: importance of the N-terminal region between cysteine 3 and cysteine 13. Biochemistry 1992; 31:10146-10152
177. Boden MK, Harber GJ, Birkedal-Hansen B, et al. Functional domains of human TIMP-1 (tissue inhibitor of metalloproteinases). J Biol Chem 1994; 269:18943-18952
178. Mauviel A. Cytokine regulation of metalloproteinase gene expression. J Cell Biochem. 1993; 53: 288-95.
179. Delany AM, Brinckerhoff CE. Post-transcriptional regulation of collagenase and stromelysin gene expression by epidermal growth factor and dexamethasone in cultured human fibroblasts. J Cell Biochem. 1992; 50: 400-10.
180. Wolf C, Rouyer N, Lutz Y, et al. Stromelysin 3 belongs to a subgroup of proteinases expressed in breast carcinoma fibroblastic cells and possibly implicated in tumor progression. Proc Natl Acad Sci U S A. 1993; 90: 1843-7
181. Bian JH, Sun Y. Transcriptional activation by P53 of the human type IV collagerase (Gelatinase A or matrix metalloproteinse 2) promoter. Molecular and Cellular Biology. 1997; 17:6330-6338
182. Madri JA, Basson MD. Extracellular matrix-cell interactions: dynamic modulators of cell, tissue and organism structure and function. Lab Invest. 1992; 66: 519-21.
183. Springman EB, Angleton EL, Birkedal-Hansen H, et al. Multiple modes of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active-site zinc complex in latency and a "cysteine switch" mechanism for activation. Proc Natl Acad Sci U S A. 1990; 87:364-8
184. Grignon DJ, Sakr W, Toth M, et al. High levels of tissue inhibitor of
metalloproteinase-2 (TIMP-2) expression are associated with poor outcome in invasive bladder cancer. Cancer Res. 1996 1; 56: 1654-9.
185. Leco KJ, Khokha R, Pavioff N, et al. Tissue inhibitor of metalloproteinaes-3 (TIMP-3) is extracellular matrix-associated protein with a distinction pattern of expression in mouse cells and tissues. J Biol Chem 1994; 269:9352-9360
186. Campbell CE, Flenniken AM, Skup D, et al. Identification of a serum and phorbol ester-responsive element in the murine tisse inhibitor of metalloproteinase gene. J Biol Chem 1991; 266:7199-7206
187. Edwards DR, Rocheleau H, Sharma RR, et al. Involvement of AP1 and PEA3 binding sites in the regulation of murine tissue inhibitor of metalloproteinases (TIMP-1) transcription. Biochem Biophys Acta 1992; 1171:41-55
188. Leco KJ, Hayden LI. Sharma RR, et al. Differential regulation of TIMP-1 and TIMP-2 mRNA expression in normal and Ha-ras-transformed murine fibroblasts. Gene 1992; 117:209-217
189. DeClerck YA, Dartll MI, Eeckhout Y, et al. Characterization of the promoter of the gene encoding human tissue inhibitor of metalloproteinases-2 (TIMP-2). Gene 1994; 139:185-191
190. Uchijima M, Sato H, Fujii M, et al. Tax proteins of human T-cell leukemia virus tpe 1 and 2 induce expression of the gene encoding erythroid potentiating activity (tissue inhibitor of metalloproteinases-1, TIMP-1). J Biol Chem 1994; 269:14526-14950
191. Ponton A, Coulomte B, Steyaert A, et al. Basal expression of the gene (TIMP) encoding the murine tissue inhibtor of metalloproteinases is medicated through AP1- and CCAAT-binding factors. Gene 1992; 116:187-194
192. Gaire M, Magbanul Z, McDonnell S, et al. Structure and expression of the human gene for the matrix metalloproteinase matrilysin. J Biol Chem 1994; 269:2032-2040
193. Nomura S, Hogan 3LM, Wills AJ, et al. Developmental expression of tissue inhibitor of metalloproteinase (TIMP) RNA. Development 1989; 105:575-583
194. Waterhouse P, Denhardt DT, Khokha R. Temporal expression of tissue inhibitors of metalloproteinases in mouse reproductive tissues during gestation. Mol Reprod Dev 1993; 35:219-226
195. Apte SS, Hayashi K. Seldi MF, et al. Gene encodng a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage and muscle and is located on mouse thromosome 10. Develop Dynam 1994; 200:177-179
196. Stricklin GP, Liying L, Jancic V et al. Localization of mRNAs representing collagenase and TIMP in sections of healing human burn wounds. Am J pathol. 1993; 143:1657-1666
197. Inoue M, Kratz G. Haegerstrand A, et al. Collagenase expression is rapidly induced in wound-edge keratinocytes after acute injury in human skin, persists during healing, and stops at re-epithelialization. J Invest Dermatol. 1995; 104: 479-83.
198. Weckroth M, Vaheri A, Lauharanta J, et al. Matrix metalloproteinases, gelatinase and collagenase in chronic leg ulcers. J Invest Dermatol 1996; 106:1119-1124
199. Howard EW, Bullen EC, Banda MJ: Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem 1991; 266:13064-13069
200. Kjeldsen L, Sengelov H, Lollike K, et al.Isolation and characterization gelatinase granules from human neutrophils. Blood. 1994; 83:1640-1649
201. Murphy G, Willenbrock F, Ward RV, et al. The C-terminal domain of 72-kDa gelatinase A is not required for catalysis, but essential for membrane activation and modulates interactions with tissue inhibitors of metalloproteinases. Biochem J. 1992; 283:637-641
202. Barone EJ, Yager DR, Pozez AL, et al. Interleukin-12 and collagenase activity are elevated in chronic wounds. Plast Reconstr Surg 1998; 102:1023-1027
203. Heckmann M, Adelmann-Grill BC, Hein R, et al. Biphasic effects of interleukin-12 on dermal fibroblasts: enhancement of chemotactic responsiveness at low concentrations and of mRNA expression for collagenase at high concentrations. J Invest Dermatol. 1993; 100:780-788
204. Fini ME, Strissel KJ, Girarcl MT, et al. Interleukin-1 mediates collagenase synthesis stimulated by phorbol 12-myristate 13-acetate. J Biol chem. 1994; 269:11291-11295
205. Grinnell F, Zhu ME Parks WC. Collagenase-1 complexes α_2_macroglobulin in the acute and chronic wound environments. J Invest Dermatol. 1998; 110:771-776
206. Stricklin GP, Li LY, Nanney LB. Localization of mRNAs TIMP in healing porcine burn wounds. J Invest Dermatol. 1994; 103:352-358
207. Nwomeh BC, Liang HX, Cohen IK, et al. MMP-8 is the prcdominant collagenase in healing wounds and nonhealing ulcers. J of surg Res. 1999; 81:189-195
208. Bedi GS, Williams T. Purification and characterization of a collagen degrading protease from porphyromonas gingivalis. J Biol chem. 1994; 269:599-606
209. Cook H, Stephens P, Davies KJ, et al. Defective extracellular matrix reorganization by chronic wound fibroblasts is associated with alterations in TIMP-1, TIMP-2, and MMP-2 activity. J invest Dermatol 2000; 115:225-233
210. Soo C, Shaw ww, Zhang XL, et al. Differential expression of matrix metalloproteinases and their tissue-derived inhibitors in cutaneous wound repair.
Plast Reconstr Surg 2000; 105:638-647
211. Zeng GY, Millis AJT. Expression of 72-kDa gelatinase and TIMP-2 in early and late passage human fibroblasts. Exp cell Res 1994; 213:148-155
212. West MD, shay JW, Wright WE, et al. Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence. Exp Gerantol 1996; 31:175-193
213. Ashcroft GS, Herrick SE, Tarnuzzer RW, et al.Human aging impairs injury-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1 and —2 protein and mRNA. J Pathol. 1997; 183:169-176
214. Wick M, Burger C, Brusselbach S, et al.A novel member of human tissue inhibitor of metalloproteinases is regulated during G1 progression, mitogenic stimulation, differentiation, and senescence. J Biol Chem. 1994; 269:18953-18960
215. Johansson N, saarialho-kere UK. Hypertrophic chendrocytes, periosteal cells and osteoblasts express Airolak, et al. Collagenase-3 (MMP-3) during fetal bone development. Dev Dyn 1997; 28:387-395
216. Kheradmand F,Werner E,Tremble P, et,al. Role of rac-1 and oxygen radicals in collagenase-1 expression induced by cell shape change. Science 1998; 280:898-902
217. Lovejoy B, Cleasby A, Hassell AM, et al. Sturcture of the catalytic domain of fibroblast collagenase complexed with an inhibitor. Science 1994; 263:375-377
218. Massova I, Kotra LP, Fridman R, et al. Matrix metalloproteinases: structures, evolution, and diversification. FASEB J 1998; 12:1075-1095
219. Parks WC. Matrix metalloproteinases in repair. Wound Repair Regen 1999; 7:423-432
220 石冰，陈绍宗，张萍等。封闭负压引流对人慢性创面中金属基质蛋白酶的影响。中国美容医学杂志。2003；12：10—13
221. Suomalainen K, Sorsa T, Golub LM, et al. Specificity of the anticollagenase action of tetracyclines: relevance to their anti-inflammatory potential. Antimicrobial Agents chemother 1992; 36:227-229
222. Sorsa T, Ding Y, salo T, et al. Effects of tetracyclines on neutrophl, gingival and salivary collagenases. A functional and western-blot assessment with special reference to their cellular sources in periodontal diseases. Ann NY Acad Sci 1994; 732:112-131
223. Lanhio A, Salo T, Ding Y, et al. In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and NSAID in acute reactive arthritis. Clin Exp Immunol 1994; 98:21-28
224. YU LP, Smith GN, Hasty KA, et al. Doxycycline inhibits type ⅩⅠ
collagenolytic activity of extracts from human osteoarthritic cartilage and of gelatinase J Rheumatol 1991; 18:1450-1452
225. Greenwald R, Golub LM, Lavietes B, et al. Tetracyclines inhibit human synovial collagenase in vivo and in vitro. J Rheumatol 1987; 14:28-32
226. Wallace HJ, Stacey MC. Levels of tumor necrosis factor-α (TNF-α) and soluble TNF receptors in chronic venous leg ulcers correlations to healing status. J Invest Dermatol 1998; 110:292-296
227. Trengove N, Langton S, Stacey M. Biochemical analysis of wound fluid from nonhealing and healing chronic leg ulcers. Wound Rep Reg 1996; 4:234-239
228. Jue D, Sherry B, Luedke C, et al. Processing of newly synthesized cachectin/tumor necrosis factor in endo toxin-stimulated macrophages. Biochem.1990; 29:8371-8377
229. Schutze S, Scheurich P, Schluer C, et al. Tumor necrosis factor induced changes of gene expression in U 937 cells: Differentiation-dependent plasticity of the responsive state. J Immunol 1988; 140:3000-3005
230. Vilcek J, Palombella V, Henrikson-Destefano D, et, al. TNF soluble receptors circulate during experimental and clinical inflammation and can protect against excessive TNF-α in vitro and in vivo. Proc Natl Acad sci USA 1992; 89:4845-4849
231. Detmar M, Orfanos C. Tumor necrosis factor-alpha inhibits cell proliferation and induces class Ⅱ antigens and cell adhesion molecules in cultured normal human keratinocytes in vitro. Arch Dermatol Res 1990; 282:238-245
232. Mirshahi S, Soria J, Mirshahi M, et al.Expression of elastase and fibrin in venous leg ulcer biopsies: a pilot study of pentoxifylline vesus placebo. J cardiovasc Pharmacol 1995; 25(supp 1, 2): S101-S105
233. Higuchi M, Aggarwal B. Inhibition of ligand binding and antiproliferative effects of tumor necrosis factor and lymphotoxin by soluble forms of p60and p80 receptors. Res Commun 1992; 182:638-643
234. Scnderi P, Nez P, Duerr M, et al. Cathepsin-G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin. Cell Immunol 1991; 135:299-313
235．付小兵，顾小螟，孙同桂等，创面愈合组织三种生长相关因子表达及信号转导机制的实验研究。中华外科杂志，2001：39：714-717
236. Gu Xiaoman, Fu Xiaobing, Yang Yinhui, et al. Expression characteristics of c-fos, c-myc and bFGF in early burn tissue. Chinese Medical Journal 2001; 114:925-928
237. Cory A, Lekha P, Frank J, et al. Redox regulation of fos and Jun DNA-binding activiy in vitro. Science 1990; 249:1157-1161
238. Martin P, Nobes DC. An early molecular component of the wound healing
response in rat embryos: induction of c-fos protein in cells at the epidermal wound repair. Mech Der 1992; 38:209-216
239. Schonthal A, Herrlich P, Rahmsdorf HJ, et al. Requirment for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters. Cell.1998; 54:324-334
240. Tsuji M, Funahashi S, Takigawa M, et al. Expression of c-fos gene inhibits proteoglycan synthesis in transfected chondrocyte. FEBS Lett. 1996; 381:222-226
241. Uria JA, Jimenez MG, Galbin M, et al. Differential effects of transforming growth factor-beta on the expression of collagenase-1 and collagenase-3 in human fibroblasts. J Biol chem 1998; 273:9769-9777
242. Crowe DL, Brown TN. Transcriptional inhibition of matrix metalloproteinase 9 (MMP-9) activities by a c-fos/estrogen receptor fusion protein is mediated by the proximal AP-1 site of the MMP-9 promoter and correlates with reduced tumor cell invasion. Neoplasia 1999; 1:368-72
243. Naruo S, Kanayama H, Aki M, et al. Gene expressions of type IV collagenase and tissue inhibitor of metalloproteinases (TIMPs) in human bladder cancers. Nippon Hinyokika Gakkai Zasshi 1993; 84:841-50
244. Fu Xiaobing, Jiang Lixian, Sun Tongzhu, et al. Expression of oncoproteins c-fos and c-jun in hypertrophic scars and chronic dermal ulcers and their regulation of basic fibroblast growth factor. Chinese medical Journal 2001; 114:852-856
245. Cechowska-Pasko M, Palka J, Bankowski E. Decreased biosynthesis of glycosaminoglycans in the skin of rats with chronic diabetes mellitus. Exp Toxicol Patrol 1999; 51:239-243
246. Hehenberger K, Kratz G, Hansson A, et al. Fibroblasts derived from human chronic diabetic wounds has a decreased proliferation rate, which is recovered by the addition of heparin. J Dermatol sci 1998; 16:144-151
247. Galassi G, Brun P, Radice M, et al. In vitro reconstructed dermis implanted in human wounds: degradation studies of the HA-based supporting scaffold. Biomaterials 2000; 21:2183-2191
248. Hollander D, Stein M, BerndA, et al. Autologous keratinocytes cultured on benzyoester ulcers. J wound care 1999; 8:351-355
249. Depalma RL, Krummel TM, Durbam LA, et al.characterization and quantitation of wound matrix in fetal rabbit.Matrix.1989; 9:224-231
250. Knight.KR, Horne RS, Lepore, DA, et, al. Glycosaminoglycan composition of uninjured skin of scar tissue in fetal, newborn & adult sheep. Res Exp Med. 1994; 194:119-127
251. Longaker MT, Chiu ES, Adzick NS, et, al. Studies in fetal wound healing, V:
A prolonged presence of HA characterizes fetal wound fluid. Annals of surgery 1991; 213:292-296
252．石冰，柳大烈，马世英等．透明质酸含量在兔正常皮肤及皮肤创伤愈合过程的变化．中华医学美容杂志 1999；5：189-193
253. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998; 176(supp12A): 26s-38s
254．黄金井。真皮提取物对成纤维细胞的生长抑制作用的研究．中华整形烧伤外科杂志 1995；11：137-139