PCMV4-hTGFβ_1作为核酸疫苗在大鼠Ⅱ°烫伤创面愈合及瘢痕形成中的作用
摘要
烧伤是一种常见病，其创面处理贯穿于治疗的全部始终。创面愈合的速度和质量是评价治疗水平高低的唯一可靠指标。由于目前对烧伤创面愈合和后期瘢痕形成的机理及其影响规律缺乏确切、深入的研究，因此在一定程度上影响了烧伤治疗水平的进一步提高。烧伤不仅给病人造成极大的肉体和精神上的痛苦，也给社会及家庭带来巨大的经济负担。多年来，国内外虽然有不少学者在此领域进行了大量的研究，但在加速创面愈合及有效控制后期瘢痕形成方面至今尚无令人满意的进展。
为了克服以往烫伤模型制作上的不足，研制了新的较为理想的仪器-恒温恒压电烫仪。在此基础上，分别用小鼠和大鼠制作了不同深度的烫伤模型。发现在温度80℃，压力=0.5Kg的条件下，造成小鼠浅Ⅱ°、深Ⅱ°和Ⅲ°烫伤分别需8秒、10秒和12秒。而在大鼠上造成相同深度的烫伤则在温度=80℃，压力=1.0Kg条件下，需时6秒、9秒和12秒。而大鼠的皮肤较小鼠皮肤厚的多，说明压力在接触性烫伤的致伤因素中作用很大；同时也验证了该仪器具有安全、准确、快速、重复性好，容易操作等优点。
利用基因重组技术，将全长序列的hTGFβ_1构建至能直接在骨骼肌细胞中进行基因表达的特殊载体PCMV_4中，得到新的真核表达载体PCMV_4-TGFβ_1。将其裸DNA直接注入Ⅱ°烫伤大鼠体内，用以探讨基因治疗在促进烧伤创面愈合和控制后期瘢痕形成中的作用，探索其作为核酸疫苗的可行性，为临床治疗寻求新的突破口。即用xba Ⅰ和Hind Ⅲ双酶切hTGFβ_1 cDNA全长序列，回收获得1.36Kb的片断。用相同的酶双酶切
Burn is a kind of common illness, management of whose surface of wound should span the whole course of treatment. The only reliable criterion for assessing the level of treatment is the speed and quality of healing of wound. Due to inadequacy in study of the mechanism of healing of burn and scarring that follows and inadequacy in study of the contributing factors, further elevation of the level of treatment of burn is delayed to some extent. Burn not only makes patients physically and mentally suffer tremendously, also imposes a heavy economic burden on their families and society. Scholars at home and abroad have done a lot of work in recent years, but to date no satisfactory development has been achieved yet in speeding up of healing of the wound and effective control of scarring that follows.
To overcome the shortcomings in preparation of scald model, a new ideal instrument, constant-temperature constant-pressure electric scalding device, is developed. Using this device, models of scald of varying degree were prepared on mice and rats. It was found that, under conditions of 80℃ in temperature and 0.5Kg in pressure, the times required for creating superficial second-degree scald, deep second-
为了克服以往烫伤模型制作上的不足，研制了新的较为理想的仪器-恒温恒压电烫仪。在此基础上，分别用小鼠和大鼠制作了不同深度的烫伤模型。发现在温度80℃，压力=0.5Kg的条件下，造成小鼠浅Ⅱ°、深Ⅱ°和Ⅲ°烫伤分别需8秒、10秒和12秒。而在大鼠上造成相同深度的烫伤则在温度=80℃，压力=1.0Kg条件下，需时6秒、9秒和12秒。而大鼠的皮肤较小鼠皮肤厚的多，说明压力在接触性烫伤的致伤因素中作用很大；同时也验证了该仪器具有安全、准确、快速、重复性好，容易操作等优点。
利用基因重组技术，将全长序列的hTGFβ_1构建至能直接在骨骼肌细胞中进行基因表达的特殊载体PCMV_4中，得到新的真核表达载体PCMV_4-TGFβ_1。将其裸DNA直接注入Ⅱ°烫伤大鼠体内，用以探讨基因治疗在促进烧伤创面愈合和控制后期瘢痕形成中的作用，探索其作为核酸疫苗的可行性，为临床治疗寻求新的突破口。即用xba Ⅰ和Hind Ⅲ双酶切hTGFβ_1 cDNA全长序列，回收获得1.36Kb的片断。用相同的酶双酶切
Burn is a kind of common illness, management of whose surface of wound should span the whole course of treatment. The only reliable criterion for assessing the level of treatment is the speed and quality of healing of wound. Due to inadequacy in study of the mechanism of healing of burn and scarring that follows and inadequacy in study of the contributing factors, further elevation of the level of treatment of burn is delayed to some extent. Burn not only makes patients physically and mentally suffer tremendously, also imposes a heavy economic burden on their families and society. Scholars at home and abroad have done a lot of work in recent years, but to date no satisfactory development has been achieved yet in speeding up of healing of the wound and effective control of scarring that follows.
To overcome the shortcomings in preparation of scald model, a new ideal instrument, constant-temperature constant-pressure electric scalding device, is developed. Using this device, models of scald of varying degree were prepared on mice and rats. It was found that, under conditions of 80℃ in temperature and 0.5Kg in pressure, the times required for creating superficial second-degree scald, deep second-
引文
1．陈意生，史景泉主编．烧伤病理学．重庆．重庆出版社．1992年第一版；p1．
2. Eveline B. W. The role of growth factors in wound healing. Skin Pharmacy, 1991; 4: 175-182.
3. Sporn L. B. and Roberts A. B. Introduction: What is TGF-β? wiley, chichester (Ciba Foundation symposium 157), 1991; 1-6.
4. Beck S, DeGuzman L, Lee WP, et al. One systemic administration of TGF-β_1 reverses age or glucocorticoid impaired wound healing. J Clin Inverst, 1993; 92: 2841-2849.
5. Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound healing: single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest, 1989; 84: 640-646.
6. Herndon DN, Barrow RE, Kunkel KE, et al. Effects of recombinant human growth hormone on donor site healing in severely burned children. Ann Surg. 1990 212: 424-431.
7. Gilpin DA, Barrow RE, Rutan RL, et al. Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns. Ann Surg, 1994; 220: 19-24.
8. Hatz RA, Niedner R. Vanscheidr W. et al. Wound healing and wound management. Springer-verlag Berlin Heidelberg, 1994: 151.
9. Flanga M, Growth factors and wound healing. Wound Healing, 1993; 11: 667-675.
10. Davidson JM, Broadley KN. Quaglino D. Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor-β_1 therapy. Wound Rep Reg, 1997; 5: 77-88.
11. Massague J. The transforming growth factor beta family. Ann Rev Cell Biol, 1990; 6: 597-642.
12. Barnard JA, Lyons RM and Moses HL. The cell biology of transforming growth factor β Biophys. Acat, 1990; 1032: 79-87.
13．周延冲，马贤凯．唐佩弦等．多肽生长因子基础与临床．北京．中国科学技术出版 社.1992年第一版;P234.
14. DERYNCK R, Jarrett JA, Chen EY. et al. Human transforming growth factor-beta CDNA sequence and expression in tumor cell lines. Nature, 1985; 316: 701-705.
15. Masui, T. Wekefield, L.M lechner J.E. Type beta transforming growth factor is the primany differentiation-inducing serum factor for normal human bronchial epithelial cells.Proc Natl Acad Sci USA, 1986; 83: 2438-2442.
16. Moses HL. Tucker R.F. Leof E.B. et al. type beta transforming growth factor is a growth stimulator and a growth inhibitor. Cancer Cells (cold spring Harber), 1985; 3: 65-71.
17. Tucker RF, Shipley GD, Moses HL. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science, 1984; 226: 705-707.
18. Frater-Schroder M. Muller G., Birchmeier W. et al. Transforming growth factor-β inhibits endothelial cell proliferation. Biochem Biophys Res Commun. 1986; 137: 295-302.
19. Whal SM, Hunt DA, Wakefield LM. Transforming growth factor-β induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sic USA, 1987; 84: 5788-5792.
20. Buckley-sturrock A, Wood W, Senior RM, et al. Differential stimulation of collagenase and chemotactic activity in fibroblasts derived from root wound repair tissue and human skin growth foctors. J Cell Physical. 1989: 138: 70-78.
21. Postlethwaite AE, Keski-Oja J, Moses HL, et al. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med, 1987:165: 251-256.
22. Roberts AB, Heine UI, Flanders KC, et al. Transforming growth factor β. In:Fleischmajer R, olsen BR, kiihn k(eds). Smuture. Molecular Biology, and pathology of collagen. Ann NY, Acad Sci, 1990; 580: 225-232.
23. Roherts AB, Sporn MB, Assoian PK, et al. Transforming growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA, 1986; 83: 4167-4171.
24. Peltonen J, Kahari L, Jaakkola S, et al. Evaluation of transforming growth factor β(TGF-β) and type I procollagen gene expression in fibrotic skin diseases by in situ hybridization. J Invest Dermatol, 1990; 94: 365-371.
25. Gruschwitz M, Miiller PK, Sepp N, et al. Transcription and expression of transforming growth factor type beta in the skin of progressive systemic sclerosis: a mediator of fibrosis? J Invest Dermatol, 1990; 94: 197-203.
26. Massague J. Receptors for the TGFβ family. Cell, 1992; 69: 1067-1070.
27. Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo Science, 1990; 247: 1465-1468.
28. Wolff JA, Ludtke JJ. Acsadi G, et al. A long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet, 1993; 1: 363-369.
29. Wolff JA, Dowty ME, Jiao S, et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J Cell Science, 1992; 103: 1249-1259.
30. Sikes ML, O'malley BW, Finegold MJ, et al. In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum Gene Ther, 1994; 5: 837-844.
31. Meyer KB. Intratracheoal gene delivery to the mouse airway: Characterization of plasmid DNA expression and pharmacokinetics. Gene Therapy, 1995; 2: 450-460.
32. Evans CH, Rodins PD. Gene therapy for arthritis, In: Wolff JA (ed). Gene Therapeutics. Methods and Applications of direct Gene Transfer. Birkhauser: Boston. 1994: 320-343.
33. Schwartz B, Benoistc, Abdallah B, et al. Gene transfer by naked DNA into adult mouse brain Gene Therapy, 1996; 3: 405-411.
34. Takehara T, Hayashi N, Yamamoto M, et al. In vivo gene transfer and expression in rat stomach by submucosal injection of plasmid DNA. Hum. Gene Ther, 1996; 7: 589-593.
35. Budker V, Zhang G, Knechtle S, et al. Naked DNA delivered introportally expresses efficiently in hepatocytes. Gene Therapy, 1996; 3: 593-598.
36. Dankol, Wolff JA. Direct gene transfer into muscle. Vaccine, 1994; 12: 1499-1502.
37. Ulmer JB, Peck RR, Dewitt CM, et al. Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines. Vaccine. 1994; 12: 1541-1544.
38. Davis HL, Michel ML, Mancini M, et al. Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine, 1994: 12: 1503-1509.
39. Morgan RA, Walker R. Gene therapy for AIDS using retroviral mediated gene transfor to deliver HIV-1 antisense TAR and transdominant rev protein genes to syngeneeic lymphocytes in HIV-1 infected identical twins. Hum Gene Ther, 1996; 7: 1281-1206.
40. Qin HX, Chatterjee SK. Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF. Hum gene Ther, 1996; 7: 1858-1860.
41. Sugary S, Fujitak, Kikuchi A, et al. Inhibition of tumor growth by direct intratumoral gene transfer of herpes simplex virus thymidine kinase gene with DNA-Liposome complexes. Hum Gene Ther, 1996; 7: 223-230.
42．Younai S．Venters G．vu S．et al．全军防原医学研究作会：防原医学科研资料选编：军事医学科学院一所：放射性复合烧伤的实验(1)．1974：p196-207．
43．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社．1996年第一版；p1-2．
44. Dtagert M, Ehrlich SD. Prolonged incubation in calcium chloride improves the competence of Escherichia Coli cells. Gene, 1979; 6: 23-27.
45. Cohen SN. Chang ACY, Hsu L. Nonchromosmal antibiotic resistance in bacteria: Genetic transformation of Escherchia Coli by R- factor DNA. Proc Natl Acad Sci USA. 1972; 62: 2110-2114.
46. Birnbiom HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res, 1979; 7: 1513-1517.
47. Ish-Horowicz D, Burke JF. Rapid and efficient cosmid cloning. Nucleic Acids Res, 1981; 9: 2989-2994.
48. Sugio K, Ishida T, Yokiyama H, et al. Ras gene mutations as a prognostic markers in adenocarcinoma of the human lung without lymph node metastasis. Cancer Res, 1992; 52 2903-2906.
49．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社．1996年第一版；P19．
50. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning. A Laboratory Manual., 2nd, eds, Cold Spring Harbor Laboratory. Press, Cold Spring Harbor, New York. 1989: P1.38-1.39
51．彭秀玲，袁汉英．基因工程实验技术．长沙．湖南科学技术出版社．1987年第一版：P48-59．
52．龙建银，张宏权，王会信．人转化生长因子β1 cDNA在哺乳动物细胞中表达的研究．第一届多肽生长因子基础与临床研讨会论文摘要．1994：10：31-33．
53. Andersson S, Davis DN, Dahlback H, et al. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem, 1989; 264: 8222-8229.
54. Kohn DB. The current status of gene therapy using hematopoietic stem cells. Curr Clin Pediatr, 1995; 7: 56-63.
55. Kotin RM. Prospects for the use of adeno-associated virus as a vector for human gene therapy. Hum Gene Ther, 1994; 5: 793-801.
56. Boris-Lawrie K, Temin HM. The retroviral vector. Replication cycle and safety considerations for retrovirus-mediated gene therapy. Ann Necl Acad Sci, 1994; 716: 59-70.
57. Yang Y, Li Q, Ertl HCJ, et al. Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol. 1994; 69: 2004-3015.
58. Smith C. Retrooiral vector-mediated gene transfer into hematopoietic cells: Prospects and issues, J Hematother, 1992; 1: 155-166.
59. Rosenfield MA, Ronald G, Crystal RG. Gene therapy for pulmonary diseases. Pathol Biol, 1993; 41: 677-680.
60. Halbert CL, Alexander IE, Wolgamot GM, et al. Adeno-associated virus vectors transduce primary cells much less efficiently than immortalized cells. J Virol, 1995, 69: 1473-1479.
61. Glorioso JC. Goins WF, Fink DJ, et al. Herpes simplex virus vectors and gene transfer to the brain. Dev Biol Stand, 1994; 82: 79-87.
62. Goldman MJ, Litzky LA, Engelhardt JF, et al. Transfer of the CFTR gene to the lung of nonhuman primates with El-deleted, E2-defective recombinant adenoviruses: a preclinical toxicology study. Hum Gene Ther, 1995; 6: 839-851.
63. Murphy E. Gene therapy's growing pains. Science, 1995; 269: 1052-1053.
64. Vile RG, Russell SJ. Retroviruses as vectors. Br Med Bull, 1995; 51: 12-30.
65. Strayer DS. Milano J. SV40 mediates stable gene transfer in vivo. Gene Therapy, 1996: 3: 581-587.
66．卢圣栋主编．现代分子生物学实验技术．北京．高等教育出版社．1993年第一版：P277．
67．Sambrook J．Fritsch EF．Maniatis T．(金冬雁，黎孟枫译)分子克隆实验指南．北京．科学出版社．1992年第二版；p474-479．
68．SambrookJ，Fritsch EF，Maniatis T．(金冬雁，黎孟枫译)分子克隆实验指南．北京．科学出版社．1992年第二版；p463-469．
69．林万明主编．临床基因探针诊断实验技术．上海．上海科学技术出版社．1993年第一版；p17-18．
70．林万明主编．PCR技术操作和应用指南．北京．人民军医出版社．1993年第一版：p28-56．
71．高亚兵，熊兰琦，赵波等．几种修复P53蛋白抗原免疫组化方法的比较．解放军医学杂志，1995：20：461-462．
72．苏慧慈：质粒杂交．北京冲国科学技术出版社．1994年第一版；p59-229．
73．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社．1996年，第一版：P128-141．
74. Michalski JP. A modified double antibody sandwich enzyme-linked immunosorbent assay for measurement of alphal-antitrypsin in biologic fluid. J Immun met, 1985: 83: 101-112.
75．龚志锦，詹容洲．病理组织制片和染色技术．上海．上海科学技术出版社．1994第一版；P48-52．
76．龚志锦，詹容洲．病理组织制片和染色技术．上海．上海科学技术出版社．1994 第一版；P271．
77．黎鳌主编．烧伤治疗学．第2版．北京．人民卫生出版社，1995，p18-24．
78. Peacock EE: Wound repair, Philadelphia W. B Saunders, 1984.
79．张乐鸣．伤口愈合的现代概念．《国外医学》创伤与外科基本问题分册，1987；3：129-132．
80. Hunt TK. Basic principles of wound healing. J Trauma, 1990; 30(12 Suppl): s122-128.
81. Clark RA. Growth factors and wound repair. J Cell Bioch, 1991; 46: 1-2.
82. Kingsnorth AN and Slavin J. Peptide growth factors and wound healing. Br J Surg, 1991; 78: 1286-1290.
83. Logan A, Berry M, Gonzalez AM, et al. Effects of transforming growth factor β1 on scar production in the injured central nervous system of the rat. Eur. J Nouros, 1994; 6: 355-363.
84. Younai S, Venters G, Vus, et al. Role of growth factors in scar contraction: an in vitro analysis. Ann Plast Surg, 1996; 36: 495-501.
85. Assoian Rk: The role of growth factors in tissue repair Ⅳ: Type beta transforming growth factor and stimulation of fibrosis. In the molecular and cellular, Biology of Wound Repair, edited by clark RAF, Henson PM. P273, New York, Plenum Press. 1988.
86. Hatz RA, Niedner R, Vanscheidt W, et al (eds). Wound Healing and Wound Management. Springer-Verlag Berlin Heidelberg, 1994; 1-11.
87. Brown GL, Curtsinger LJ, White M, et al. Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann Surg, 1988; 208: 788.
88. Drorak HK. Tumor: Wound do not heal. N Engl J Meal, 1986; 315: 1650-1659.
89. Sporn MB, Roberts AB, Eds. Peptide growth factors and their receptors Ⅰ Berlin: Springer-verlag, 1990; 419-472.
90. Muller G. Inhibitory actin of transforming growth factor-β on endothelial cells. Proc Natl Acad Sci USA, 1987; 84: 5600-5604.
91. Sporn MB, Roberts Ab, Wakefield LM, et al. Transforming growth factor-β biological function and chemical structure. Science, 1986; 233: 532-534.
92. Scott PG, Ghahary A, Chambers MM, et al. Biological basis of hypertrophic scarring. In: Advances in structural biology. Greenwich, CT: JAI Press, 1994; 3: 157-201.
93. Deitch EA, Wheelahan TM, Rose MP. Hypertrophic burn scars: analysis of variables. J trauma, 1983; 23: 895-899.
94. Roberts AB, Sporn MB, Handbook of experimental peptide growth pharmacology. Factors and their receptors. Heidelberg: Springer-Verlag. Berlin, 1990; 7-8.
95. Scott PG, Ghahary A, Chambers MM. et al. Biological basis of hypertrophic scarring,In: Advances in structural biology Vol3 JAI press Inc. Greenwich, Connecticut, 1994;157-201.
96. Evelime BW. The role of growth factors in wound healing, Skin pharmacol, 1991; 4:175-182.
97. Ignotz RA. Transforming growth factor beta stimulates the expression of fibronectin and collagen and their incorporation into the extracelluar matrix. J Biol Chem, 1986; 261:4337-4345.
98. Overall CM, Wrana JL, Sodek J. Independent regulation of collagenase, 72KD-progelatinase, and metalloendoprotinase inhibitor(TIMP) expression in human fibroblasts by transforming growth factor-β. J Biol chem, 1989; 264: 1860-1869.
99. Fieyel VD, Knighton DR. Transforming growth factor-beta causes indirect angiogenesis by recruiting monocytes. FASEB (Fed Am Soc Exp Biol) J 2:A.1601(Abstr). 1994.
100. Montesano R, Orci L. Transforming growth factor -β stimulated collagen matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci USA,1988; 85: 4894-4897.
101. Desmouliere A, Geinoz A. Gabbiani F, et al. Transforming growth factor -β induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing fibroblasts. J Cell Bilo, 1993; 103-111.
102. Ehrlich HP. The role of nonnective tissue matrix in wound and fracture healing. In: Barbul A, et al. Eds. Growth factors and other aspects of wound healing. New York:Liss, 1988: 243-258.
103. Logan A, Berry M, Gonzalez AM, et al. Effects of transforming growth factor-β_1 on scar production in the injured central nervous system of the rat. Eur J Neuro, 1994; 6: 355-363.
104. Shah M, Foreman DM, Ferguson MWJ. Control of scarring in adult wounds by neutralizing antibody to transforming growth factor-β. Lancet, 1992; 339: 213-214.
105. Schodel F, Aguado MT, Lambert PH. Introduction: Nucleic acid vaccines, WHO. Geneva. Vaccine, 1994; 12: 1491-1492.
106. Robinson HL, Hunt LA, Webster RG. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine, 1993; 11: 957-960.
107. Stratford-perricaudet LD, Maken I, Perricandet M et al. Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest, 1992; 90: 626-630.
108. Wolff JA, Dowty ME, Jiao S, et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T- tubules and calveolae of mammalian skeleted muscle. J Cell Sci, 1993; 103: 1249-1259.
109. Smith KT, Shepherd AJ. Boyd JE, et al. Gene delivery systems for use in gene therapy: an overview of quality assurance and safety issues. Gene Therapy, 1996; 3: 190-250.
110. Wolff JA, Ludthe JJ, Acsadi G, et al. A long-term persistenceof plasmid DNA and foreign gene expression on mouse muscle. Hum Mol Genet, 1992; 1: 363-369.
111．黎鳌主编．烧伤治疗学．第2版．北京．人民卫生出版社，1995：p538-540．
112．张涤生，李青峰．我国整形外科现状与二十一世纪展望．中华整形烧伤外科杂志．1997；1-4．
113. Cornell K, Waters DJ. Impaired wound healing in the cancer patient: effects of cytotoxic therpy and pharmacologic modulation by growth factors. Vet Clin North Am Small Anim Pract, 1995; 25: 111-131.
114. Border WA, Okuda S, Languino LR, et al. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor-β_1 Nature, 1990; 346: 371-374.
115．张树欣．肌成纤维细胞与疤痕组织．中华整形烧伤外科杂志．1987；3：229-232．
116．宋维铭，管正玉，孙广慈等．体外观察维甲类药物对人体皮肤成纤维细胞的抑制作用．中华整形烧伤外科杂志，1992；8：218-220．
117．高庆新，吴文祥，张涤生等．疤痕成纤维细胞培养和生长动力学的研究．中华整形烧伤外科杂志，1993；9：379-382．
118. Diegelmann RF, Cohen IK, McCoy BJ. Growth kinetics and collagen synthesis of normal skin, normal scar, and keloid fibroblasts in vitro. J Cell Physiol, 1979; 98: 341.
119. Russell JP, Witt WS. Cell size and growth characteristics of cultured fibroblasts isolated from normal and keloid tissues. Plast Reconstr Surg, 1976; 57: 207.
120. Russell SB, Trupin KM, Rodriguez-Eatons et al. Reduced growth factor requirements of keloid derived fibrroblasts may account for tumor growth. Proc, Natl Acad Sci USA, 1988; 85: 587.
121. Cohen IK, Beaven MA, Horakova A, et al. Histamine and collagen synthesis in keloid and hypertrophic scar. Surg forum, 1972; 23: 509.
122．姜泊，张亚历月殿元．分子生物学常实验方法．北京．人民军医出版社，1996年第一版．p157-161．
123. Felgner PL, Gadek TR, Helm M, et al. Lipofection: A highly efficient, lipid mediated DNA-transfection procedure. Proc Natl Acad Sci USA, 1987; 84: 7413.
124．司徒镇强．吴军正主编．细胞培养．陕西．世界图书出版公司．1996年第一版．p186-187．
125．司徒镇强，吴军正主编．细胞培养．陕西．世界图书出版公司，1996年第一版，p183-185．
126. Tuker RF, Shipley GD, Moses HL, et al. Growth inhibitor from BSC-1 cells is closely related to the platelet type β transforming growth factor. Science, 1984; 226: 705-707.
127. Keski-Oja J, Lyons RM, Moses HL. Immunodetection and modulation of cellular growth with antibodies against native transforming growth factor-β. Cancer Res, 1987: 47: 6451-6458.
128. Arteaga CL, Coffey RJ, Ougger TC, et al. Growth stimulation of human breast cancer cells with antitransforming growth factor β. Cell Growth & Differ, 1990; 1: 367-374.
129. Hafez MM, Infante D, Winawer S, et al. Transforming growth factor β acts as an autocrine-negative growth regulator in colon enterocytic differentiation but not in goblet cell maturation. Cell growth & Differ, 1990; 1: 617-626.
130．李英春．重组人α-干扰素瘢痕成纤维细胞生物学作用的研究．第四军医大学硕士学位论文，1996；p25-34．
131. Roberts AB, Flanders KC, Kondaiah P. et al. Transforming growth factor beta: biochemistry and roles in embryogenesis, tissue repair and remodeling; and carcinogenesis. Recent prog Horm Res, 1988; 44: 157-197.
132. Roberts AB, Sporn MB, Assoian RK, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA, 1986; 83: 4167-4171.
133. Wahl SM, Hunt DA, Wakefield LM, et al. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA, 1987; 84: 5788-5792.
134．汪良能，高学书主编．整形外科学．北京．人民卫生出版社，1989：p318-320．
135. Gaston P. Quaba AR. The pulsed tuneable dye laser as an aid in the management of postbum scarring. Burns, 1996; 22: 203-205.
136．黎鳌主编．烧伤治疗学．第二版．北京．人民卫生出版社，1995；p538-545．
137. Lee SM. Ngim CK, Chan YY, et al. A comparison of sil-k and epiderm in scar management. Bums, 1996; 22: 483-487.
138. Gabiani G. Granulation tissue as a contractile organ: A study of structure and function. J Exp Med, 1972; 135: 719.
139．李永林．瘢痕挛缩机理的研究和生物学治疗进展，《国外医学》创伤与外科基本问题分册．1997：18：7-9．
140．贾赤宇．张键．胚胎无瘢痕愈合的研究进展．《国外医学》创伤与外科基本问题分册．1997；18：9-12．
141．扬松林，何清濂，林子豪等．瘢痕成纤维细胞三维培养的实验研究冲华整形烧伤外科杂志，1996；12：2-5．
142. Sahara K, Kucukcelebi A, Francis KO, et al. Suppression of in vitro proliferative scar fibroblast contraction by interferon alfa-2b. Wound Rep Reg, 1993; 1: 22-27.
143. Choi BM, Kwak HJ, Jun CD, et al. Control of scarring in adult wounds using antisense transforming growth factor β_1 oligodeoxynucleotides. Immun Cell Biol, 1996; 74: 144-150.
144. Schurch W, Seemayer TA, Gabbiani G. Myofibroblast. In: Sternberg SS, editor. Histology for pathologister. New York, Raven Press, 1992: 109-144.
145. Janssen H, Rooman R and Robertson JIS. Wound Healing, UK, wrightson Biomedical Bublishing 1td, 1991; 103-115.
146．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社，1996：p152．
147．杨建涛，吴曼．哺乳动物细胞的基因转染．《国外医学》分子生物学分册，1987：9：106-110．
148. Bascom CC, Wolfshohl JR, Coffey RJ, et al. Complex regulation of transforming growth factor β1 β2 and β3 mRNA expression in mouse fibroblasts Keratinocytes by transforming growth factor β1 and β2. Mol Cell Biol, 1989; 9: 5508-5515.
149. Schwarz LC, Wright JA, Gingras MC, et al. Aberrant TGFβ production and regulation in metastatic malignancy. Growth factors, 1990; 3: 115-127.
150. Coffin JM. Molecular mechanisms of nucleic acid integration. J Med, Vivo, 1990; 31: 43-49.
151. Massagne J. The transforming growth factor beta family Ann. Rev Cell Biol. 1990; 6: 597-642.
152. Moses HL, Tucker RF, Leof EB, et al. Type β transforming growth factor is a growth stimulator and a growth inhibitor. Cancer Cells, 1985; 3: 65-71.
153. Cochrane CA, Freeman KL, Knottenbelt DC, et al. Effect of growth factors on the characteristics of cells associated with equine wound healing and sarcoid formation. Wound Rep Reg, 1996; 4: 58-65.
154. Roberts AB, Anzano MA, Wakefield LM, et al. Type β transforming growth factor: A bifunctional regulator of cellular growth. Proc Natl Acd Sci, USA, 1985; 82: 119-123.
1．程天民主编．创伤战伤病理学．第11版．北京．解放军出版社，1992；28-29．
2. Rockwell WB, Cohen IK, Fhrlich HP. Keloids and hypertrophic scars: a comprehensive review. Plast Reconstr Surg, 1989; 84: 827-831.
3. Holtz G. Prevention and management of peritoneal adhesions. Fertil steril, 1984; 41: 496-507.
4. Sahara K, Kucukcelebi A, Francis KO, et al. Suppression of in vitro proliferative scar fibroblast contraction by interferon alfa-2b. Wound Rep Reg, 1993; 1: 22-27.
5. Falanga A, Grinnel F, Gilchrest B, et al. Experimental approaches to chronic wounds. Wound Rep Reg, 1995; 3: 132-140.
6. Browse N. The pathogenesis of venous ulceration. J Vasc Surg, 1988; 7: 468-672.
7. Falang V. Chronic wounds: Pathophysiologic and experimental considerations. J Invest Dermatal, 1993; 100: 721-725.
8. Falanga V, Grinnell F, Gilehrest B, et al. Workshop on the pathogenesis of chronic wounds. J Invest Dermatol, 1994; 102: 125-127.
9. Kirsner RS, Eaglstein WH. The wound healing process. Dermatol Clin, 1993; 11: 629-640.
10. Hammar. H. Wound healing. Int J Dermatol, 1993; 32: 6-15.
11. Clark RAF. Cutaneous wound repair: Molecular and cellular controls. Drog Dermatol, 1988; 22: 1-12.
12. Sempowski GD, Borrello MA, Blieden TM, et al. Fibroblast heterogeneity in the healing wound. Wound Rep Reg, 1995; 3: 120-131.
13. Tredget EE. The molecular biology of fibroproliferative disorders of the skin: Potential cytokine therapeutics. Ann Plast Surg, 1994; 33: 152-154.
14. Cherry GW. The past present and future of wound healing. Wound Rep Reg, 1995; 3: 119.
15．张乐鸣．伤口愈合的现代概念．《国外医学》创伤与外科基本问题分册，1987；3：129-132．
16. Hunt TK. Basic principles of wound healing. J Trauma, 1990; 30: (12 Suppl): s122-128.
17. Orgill D, Demling Rh. Current concepts and approaches to wound healing. Crit Care Med, 1988; 16: 899-907.
18. Schilling JA. Wound healing. Surg Clin North Am, 1976; 56: 869-874.
19. Sporn MB, Roberts AB, Eds. Peptide growth factors and their receptors Ⅱ. Berlin: Springer-Vedag, 1990; 511-524.
20. Reibman J, Meixler S, Lee TC, et al. Transforming growth factor-β_1, a potent chemoattractant for human neutrophils, bypasses classic signal transduction pathways. Proc Natl Acad Sci USA, 1991; 88: 6805-6809.
21. Cromack DT. Current concepts in wound healing: growth factor and macrophage interaction. J Trauma 1990; 30(12 Suppl): s129-133.
22. Leirisalo-Repo M. The present knowledge of the inflammatory process and inflammatory mediators. Pharmacol Toxicol, 1994; 75: 1-3.
23. Liebovich SJ, Ross R. A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol, 1976; 84: 501-504.
24. Igarashi A, Okochi H, Bradham DM, et al. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and curing wound repair. Mol Biol Cell, 1993; 4: 637-645.
25. Wahl SM. Transforming growth factor beta (TGF-β) in inflammation; a cause and a cure. J Clin Immunol, 1992; 12: 61-74.
26. Tarauzzer RW, Schultz GS. Biochemical analysis of acute and chronic wound environments. Wound Rep Reg, 1996; 4: 321-325.
27. Longaker MT, Bouhana KS, Harrison MR, et al. Wound healing in the fetus. Wound Rep Reg, 1994; 2: 104-112.
28. Dover R, Wright NA. The cell proliferation kinetics of the epidermis. In: Goldsmith LA(ed) physiology, Biochemistry, and Molecular Biology of the skin. New York: Oxford University Bess, 1991; 239-256.
29. Larson DL, Abstons, Dobrkovsky M, et al. The prevention and correction of burn scar contracture and hypertrophy. Galveston: Shriners Burns Institute, 1973; 1-21.
30. Kloth IC, Miller KH, The inflammatory response to wounding. In: Kloth IC, McCulloch JM, Feedar JA(eds) Wound Healing: alternatives in management, Philadelphia: FA Davis, 1990; 3-13.
31. Linares HA. From wound to scar. Burns, 1996; 22: 339-352.
32. Gabbiani G, Hirschel BJ, Ryan GB, et al. Granulation tissue as a contractile organ. A study of structure and function. J Exp Med, 1972;135: 719-734.
33. Ehrlich HP. Wound closure: Evidence of cooperation between fibroblasts and collagen matrix. Eye, 1988; 2: 149-157.
34. Olutoye OO, Cohen K. Fetal wound healing: An overview. Wound Rep Reg, 1996; 4: 66-74.
35. Roberts AB. Anzano MH, Lamb LC, et al. New class of transforming growth factors potentiated by epidermal growth factor. Proc Natl Acad Sci USA, 1981; 78: 5339-5343.
36. Allen JB, Manthey CL, Hand AR, et al. Rapid onset synovial inflammation and hyperplasia induced by TGFβ. J Exp Med, 1990; 171:231-247.
37. Fava RA, Olsen NJ, Postlethwaite AE, et al. TGFβ_1-induced neutrophil recruitment to synovial tissues: implications for TGFβ-driven synovial inflammation and hyperplasia. J Exp Med, 1991; 173: 1121-1132.
38. Postlethwaite AE, Keski-oja J, Mosses HL, et al. Stimulation of the chemotactic migration of human fibroblasts by TGFβ. J Exp Med, 1987;165:251-256.
39. Reibman J, Meixler S, Lee TC, et al. Transforming growth factor β_1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways. Proc Natl Acad Sci USA, 1991; 88: 6805-6809.
40. Adams DH, Hathaway DM, Shaw J, et al. Transforming growth factor-β induces T lymphocyte migration in vitro. J Immunol, 1991; 147: 609-612.
41. Koyama N, Koshikawa T, Morisaki N, et al. Bifunctional effects of transforming growth factor-β on migration of cultured rat aortic smooth muscle cells. Biochem Biophys Res Commun, 1990; 169: 725-729.
42. Massague J, Transforming growth factorβ family. Ann Rev Cell Biol,1990; 6: 597-641.
43. Rokerts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-β(TGF-β). Growth factors, 1993; 8: 1-9.
44. Mast BA, Schultz GS. Interactions of cytokines, growth factors and proteases in acute and chronic wounds. Wound Rep Reg, 1996; 4:411-420.
45. Roberts AB, Anzano MA, wakefield LM, et al. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA, 1985; 82: 119-123.
46. Like B, Massague J: The antiproliferative effect of type beta transforming growth factor occurs at a level distal from receptors for growth-activating factors. J Biol Chem, 1986; 261: 13426-13429.
47. Shipley GD, Pittelkow MR, Wille JJ Jr, et al. Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res, 1986;46:2086-2071.
48. Fratter-schroder M, Muller G, Birchmeier W, et al. Transforming growth factor-β inhibits endothelial cell proliferation. Biochem Biophys Res Comman, 1986; 137: 295-302.
49. Hebda PA: Stimulatory effects of transforming growth factor-β and epidermal growth factor and epidermal cell outgrowth from porcine skin explant cultures. J Invest Dermatol, 1988; 91: 440-445.
50. Majack RA, Majesky MW, Goodman LV, Role of PDGF-A expression in the control of vascular smooth muscle cell growth by transforming growth factor-β. J Cell Biol, 1990; 111: 239-247.
51. Beck LS, Chen TL, Mikalanski P, et al. Recombinant human transforming growth factor-beta 1 (rhTGFβ_1) enhances healing and strength of granulation skin wounds. Growth Factors, 1990; 3: 267-275.
52. 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.
53. Mcmullen H, Longaker MT, Cabrera RC, et al. Spatial and temporal expression of transforming growth factor-β isoforms during ovine excisional and incisional wound repair. Wound Rep Reg, 1995; 3: 141-156.
54. Ellis I, Grey AM, Schor AM, et al. Antagonistic effects of TGFβ_1 and MSF on fibroblast migration and hyaluronic acid synthesis. J Cell Science, 1992; 102: 447-456.
55. Quaglino D, Nanney LB, Ditesheim JA, et al. Transforming growth factor beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: incisional wound model. J Invest Dermatol,1991; 97: 34-42.
56. Leiho M, Saksela O, Keski-Oja J. Transforming growth factor-β induction of type 1 plasminogen activator inhibitor. J Biol Chem, 1987;262: 17467-17474.
57. Brown GL, Curtsinger LJ, White M, et al. Acceleration of tensile strength of incisions treated with EGF and TGF-β_1. Ann Surg, 1988; 208:788-794.
58. Roberts AB, Sporn MB, Assoian RK, et al. Transforming growth factor type β: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA,1986; 83: 4167-4171.
59. Rong H, Tang XM, Zhao Y, et al. Postsurgical intraperitoneal exposure to glove powders modulates inflammatory and immune-related cytokine production. Wound Rep Reg, 1997; 5: 89-96.
60. Massague J, Boyd FT, Adres JL, et al. TGF-β receptors and TGF-β binding proteoglycans: recent progress in identifying their functional properties. Ann NY Acad Sci, 1990; 593: 59-72.
61. Border WA, Noble NA. Transforming growth factorβ in tissue fibrosis. New Engl J Med, 1993; 331: 1286-1292.
62. Masure S, Opdenakker G. Cytokine-mediated proteolysis in tissue remodeling. Experientia, 1989; 45: 542-549.
63. Jones KA, Kadonaga JT, Rosenfield PJ, et al. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell, 1987; 48: 79-89.
64. Short NJ. Regulation of transcription: are some controlling factors more equal than other? Nature, 1987; 236: 740-741.
65. Montesano R, Orchi L, Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci USA, 1988; 85: 4894-4897.
66. Pierce GF, Berg JV, Rudolph R, et al. Platelet derived growth factor-BB and transforming growth factor beta-1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol, 1991; 138: 629-646.
67．付小兵，盛志勇．软组织创伤修复基础研究的现状与展望．解放军医学杂志，1997；22：12-13．
68. Stocum DL. Tissue restoration approaches and prospects. Wound Rep Reg, 1996; 4: 3-15.
69. Davidson JM, Broadley KN, Quaglino D. Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor-β_1 therapy. Wound Rep Reg, 1997; 5: 77-88.
70. Miller EJ, Gays. Collagen structure and function IN: Cohen IK, Diegelmann RF, Lindblad WJ, editors. Wound healing: biochemical and clinical aspects. Philadelphia: Saunders, 1992; 130-151.
71. Mast BA, The skin In: Cohen IK, Diegelmann RF, Lindblad WJ, editors Wound healing: biochemical and clinical aspects. Philadelphia: Saunders,1992; 344-355.
72. Rudolph R, VandeBerg J, Ehrlich HP. Wound contraction and scar contracture In: Cohen IK, Diegelmann RF, Lindblad WJ, editors. Wound healing: biochemical and clinical aspects Philadelphia: Saunders, 1992;177-194.
73. Merkel JR, Dipaolo BR, Hallok GG, et al. Type I and III collagen content of healing wounds in fetal and adult rats. Proc Soc Exp Biol Med,1988; 187: 493-497.
74. Lorenz HP, Chang J, Longaker MT, et al. Transforming growth factor beta 1 and 2 synergistically increase gene expression of collagen type I and III in fetal but not adult fibroblast. Surg Forum, 1993; 79: 723-725.
75. Whitby DJ, Ferguson MWJ. Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol, 1991; 147: 207-215.
76. Border WA, Ruoslahti E. Transforming growth factor-β in disease: the dark side of tissue repair. J Clin Invest, 1992; 90: 1-7.
77. Williams RS, Rossi AM, Chegini N, et al. Effect of transforming growth factorβ on postoperative adhesion formation and intact peritoneum. J Surg Res, 1992; 52: 65-70.
78. Logan A, Frautschy SA, Gonzalez AM, et al. Enhanced expression of transforming growth factorβ_1 in the rat brain after a localized cerebral injury. Brain Res, 1992; 587: 216-225.
79. Connor TB, Roberts AB, Sporn MB, et al. Correlation of fibrosis and transforming growth factor-β type 2 levels in the eye. J Clin Invest, 1989;83: 1661-1666.
80. Castilla, Prieto J, Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease: effects of interferon alfa therapy. N Engl Med, 1991; 324: 933-940.
81. Broekelmann TJ, Limper AH, Colby TV, et al. Transforming growth factor β_1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci USA, 1991; 88: 6642-6646.
82. Border Wa, Okuda S, Langnino, et al. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β_1.Nature, 1990; 346: 371-374.
83. Peltonen J, Kahari L, Jaakkola S, et al. Evaluation of transforming growth factorβ and type I procollagen gene expression in fibrotic disease by in situ hybridization. J Invest Dermatol, 1990; 94: 365-371.
84. Steenfos HH. Growth factors and wound healing. Scand J Plast Reconstr Hand Surg, 1994; 28: 95-105.
85. Sullivan M, Lorenz HP, Meuli M, et al. A model of scarless human fetal wound repair is deficient in transforming growth factor beta. J Rediatr Surg, 1995; 30: 198-202.
86. Olutoge OO, Cohen K. Fetal wound healing. Wound Rep Reg, 1996; 4:66-74.
87. Krummel TM, Michna BA, Thomas BL, et al. TGFβ induces fibrosis in a fetal wound model. J Pediatr Surg, 1988; 23: 647-652.
88. Sullivan KM, Lorenz HP, Adzick NS. The role of transforming growth factor beta in human fetal wound healing. Surg Forum, 1993; 44: 625- 627.
89. Lorenz HP, Chang J, Longaker MT, et al. Transforming growth factor β_1 and β_2 synergistically increase collagen gene expression in fetal fibroblasts but not in adult fibroblasts. Surg Fornm, 1993; 44: 723-725.
90. Roberts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-β (TGF-β). Growth factors, 1993; 8: 1-9.
91. Graycar JL, Miller DA, Arrick BA, et al. Human transforming growth factor-β_3: recombinant expression, and biological activities in comparison with transforming growth factor-β_1 and β_2. Mol Endocrinol,1989; 3: 1977-1986.
92. Cox DA. Transforming growth factor-beta 3. Cell Biol Int, 1995; 19:357-371.
93. Shah M, Foreman DM, Ferguson MWJ. Neutralization of TGFβ_1 and TGFβ_2 or exogenous addition of TGFβ_3 to cutaneous rat wounds reduces scarring. J Cell Sci, 1995; 108: 985-1102.
94. Shah M, Foreman DM, Ferguson MWJ. Neutralising antibody to TGF-betal,2 reduces cutaneous scarring in adult rodents. J Cell Sci, 1994; 107:1137-1157.
95. Serini G, Gabbiani G. Modulation of α-smooth muscle actin expression in fibroblasts by transforming growth factor-β isoforms: an in vivo and in vitro study. Wound Rep Reg, 1996; 4: 278-287.
96. Border WA, Nobel NA, Yammamoto T, et al. Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease. Nature, 1992; 360: 361-364.
97. Houghton PE, Keefer KA, Krummel TM. The role of transforming growth factor-β in the conversion from "scarless" healing to healing with scar formation. Wound Rep Reg, 1995; 3: 229-236.
1．汪美先主编．医学微生物学与免疫学．西安．陕西科学技术出版社，1989；p92-101．
2. Wolff JA, Malone RW, Willians P, et al. Direct gene transfer into mouse muscle in vivo Science, 1990; 247: 1465-1468.
3. Israel MA, Chan HW, Roroe WP, et al. Molecular cloning of polyoma virus DNA in Escherichia coli: plasmid vector system. Science, 1979; 203: 883-887.
4. Chan HW, Israel MA, Garon CF, et al. Molecular cloning of pdyoma virus DNA in Escherichia coli: lambda phage vector system. Science, 1979; 203: 887-892.
5. Schodel F, Aguado MT, Lambert PH. Introduction: nucleic acid vaccines, WHO, Geneva. Vaccine, 1994; 12: 1491-1492.
6. Lin H, Parmacek MS, Morle G, et al. Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation, 1990; 80: 2217-2221.
7. Acsadi G, Jiao S, Jani A, et al. Direct gene transfer and expression into rat heart in vivo. New Biol, 1991; 3: 71-81.
8. Sikes ML. O'malley BW, Finegold MJ, et al. In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum Gene Ther, 1994; 5: 837-844.
9. Malone RW, Hick man MA, Lehmann-Bruinsma K, et al. Dexamethasone enhancement of gene expression after direct hepatic DNA injection. J Biol Chem, 1994; 269: 29903-29907.
10. Yorandich J, O'malley B, Sikes M, et al. Gene transfer to synovial cells by intra-articular administration of plasmid DNA. Hum Gene Ther, 1995; 6: 603-610.
11. Schwartz B, Benoist C, Abdallab B, et al. Gene transfer by naked DNA into adult mouse brain. Gene Ther, 1996; 3: 405-411.
12. Raz E, Carson DA, Parker SE, et al. Intradermal gene immunication: The possible role of DNA uptake in the induction of cellular immunity to viruses. Proc Natl Acad Sci USA, 1994; 91: 9519-9523.
13．张灵生，汤健．脂质体作为基因载体的研究进展．《国外医学》分子生物学分册，1993；15：10-12．
14. Nabel EG, Gordon D, Yang ZY, et al. Gene transfer in vivo with DNA-liposome complexes: lack of autoimmunity and gonadal localization. Hum Gen Ther, 1992; 3: 649-656.
15. Davis HL, Demeneix BA, Quantion B, et al.. Plasmid DNA is superior to viral vectors for direct gene transfer in adult mouse skeletal muscle. Hum Gene Ther, 1993; 4: 733-740.
16. Stratford-Perricaudet LD, Maken I, Perricaudet M, et al, Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest, 1992; 90: 626-630.
17. Wolff JA, Dowty ME, Jiao S, et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscles. J Cell Sci, 1992; 103: 1249-1259.
18. Horwitz AF, Schotland DL. The Plasma membrane of the muscle fiber. In myology (Ed. Engel AE and Bawker BQ) New York: McGraw-Hill, p177-207.
19. Anderson RGW, Kamen BA, Rotherg KG, et al. Dotoeytosis: Sequestration and transport of small molecules by caveolae. Science, 11992; 255: 410-411.
20. Acsadi G, Jiao S, Jani A, et al. Direct gene transfer and expression into rat heat in vivo. New Biologist, 1991; 3: 71-81.
21. Whalen RG, Harris JB, Butler-Browne GS, et al. Expression of myosin isoforms during notexin-induced regeneration of rat soleus muscles. Dev Biol, 1990; 141: 24-40.
22. Davis HL, Whalen RG, Demeneix BA. Direct gene transfer into skeletal muscle in vivo factors affecting efficiency of transfer and stability of expression. Hum Gene Ther, 1993; 4: 151-159.
23. Yang MS, Burkholder J, Roberts B, et al. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad. Sci. USA, 1990; 87: 5968-5972.
24. Williams RS, Johnston SA, Riedy M, et al. Introduction of foreign genes into tissue of living mice by DNA-coated microprojectiles. Proc Natl Acad Sci USA, 1991; 88: 2726-2730.
25. Zhou X, Berglund P, Rhodes G, et al. Self-replicating scmliki forest virus RNA as recombinant vaccine. Vaccine, 1994; 12: 1520-1514.
26. Ciernik IF, Krayenbuhl BH, Carbone DP. Puncture-mediated gene transfer to the skin. Hum Gen Ther, 1996; 7: 893-899.
27. Streilein JW. Skin-associated lymphoid tissue (SALT) origins and functions. J Invest Dermatol, 1983; 80: 12-16s.
28. Streilein JW. Skin-associated lymphoid tissue. In: Immune mechanisms in cutaneous disease (Ed. Norris DA) Marcel Dekker, New York and Basel, 1998; p73-96.
29. Robinson HL, Hunt LA, Webster RG. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine, 1993; 11: 957-960.
30. Fynan EF, Webster RG, Fuller DH, et al. DNA vaccines, protective immunization by parenteral, mucosal, and gene gun inoculations. Proc Natl Acad Sci USA, 1993; 90: 11478-11482.
31.Ulmer JB, Donnelly JJ, Parker SE, et al. Heterologous proteetion against inffuenza by injection of DNA encoding a viral protein. Science, 1993;259: 1745-1749.
32. Wang B, Ugen Ke, Srikantan V, et al. Gene inoculation generates immune responses against human immunoceficiency virus type I. Proce Natl Acad Sci USA, 1993; 90: 4156-4160.
33. Webster RG, Fynan EF, Santoro JC, et al. Protection of ferrets against influenza challenge with a DNA vaccine to the haemagglutinin. Vaccine,1994; 12: 1495-1498.
34. Budker V, Zhang G, Knechthe S, et al. Naked DNA delivered introportally expresses efficiently in hepatocytes. Gene Therapy, 1996; 3:593-598.
35. Lowrie DB, Tascon RE, Colston MJ, et al. Towards a DNA vaccine against tuberculosis. Vaccine, 1994; 12: 1537-1540.
36. Hoffman SI, Sedegah M, Hedstrom RC. Protection against malaria by immunization with a plasmodium yoelii circumsporozzoite protein nucleic acid vaccine. Vaccine, 1994; 12: 1529-1533.
37. Ulmer JB, Deck RR, Dewitt Cm, et al. Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines.Vaccine, 1994; 12: 1541-1544.
38. Evans Ch, Rooddins PD. Gene therapy for arthritis. In: Wolff JA(ed).Gene Therapeutics: Methods and Applications of direct gene transfer. Birkhauser: Boston, 1994; p320-343.
39. Qin HX, Chatterjee SK. Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF. Hum Gene Ther,1996; 7:1853-1860.
40. Morgan RA, Walker R. Gene therapy for AIDS, using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant rev protein genes to syngeneic lymphocytes in HIV-infected identical twins. Hum Gene Ther, 1996; 7: 1281-1306.
41. Jiao S, Williams P, Berg RK, et al. Direct gene transfer into non-human primate myofibers in vivo. Hum Gene Ther, 1992; 3: 21-33.
1. Leak CL. The old Egyptian papyri. University of Kansas Press, Lawrece,Kansas. 1952.
2. Adams F. The genuine works of hippocrates. The sydenham society,Lodon L849.
3. Gilje O. On taping (adhesive tape treatment) of leg ulcers. Acts Derm Vener, 1948; 28: 454.
4. Linsky CB, Roree DT, Dow T. Effects of dressings on wound inflammation and scar tissue. In: The surgical wound.(Dineen P and Hildick-Smith G,eds). Lea & Febiger,philadelphia 1981; 191.
5. Pirone L, Monte K, Shannon R, et al.. Wound healing under occlusion and non-occlusion in full- and partial-thickness wounds in swine.Wounds,1990;2:74.
6. Jostkleigrewe F, Brandt KA, Flechsig G, et al. Treatment of partial thickness burns of the hand with the preshaped, semipermeable procel burn cover: results of a multicentre study in the burn centers of Berlin,Duisburg and Munich. Burns, 1995; 2: 297.
7. Sedlarik KM, Vacik J, Wichterle O. Modern dressings. Hydrogels. Rozhl Chir, 1995; 74: 3.
8. Fuller FW, Parrish M, Nance FC. A review of the dosimetry of 27 silver sulfadiazine cream in burn wound treatment. J Bum Care Rehabi1,1995:15:213.
9 Constantine B, Monte K(eds). Burn debridement under occlusion. Proceedings American Burn Association, Las Vegas, March 1990.
10. Lydon MJ, Hutchinson JJ, Rippon M, et al. Dissolution of wound coagulum and promotion of granulation tissue under DuoDerm. Wounds,1989; 1:95.
11. Kneafsey B, Oshanghnessy M,Condon KC. The use of calcium alginate dressing in deep hand burns. Burns, 1996; 22: 40.
12. WinterGD. Formation of scab and rate of epithelialization of superficial wounds in the skin of the young domestic pig. Nature, 1962; 193:293.
13. Alrarez OM. The effect of occlusive dressings on collagen synthesis and re-epithelializatio in superficial wounds. J Surgical Research, 1983; 35:142.
14. Knighton DR, Silver IA, Hunt TK. Regulation of wound healing angiogenesis-effect of oxygen concentration. Surgery, 1981; 90: 262.
15. Cherry GW, Ryan TJ. Enhanced wound angiogenesis with a new hydrocolloid dressing. The Royal Society of Medicine,1995; 88: 61.
16. Varghese MC, Balin AK, Carter DM. Local environment of chronic wounds under synthetic dressings. Arch Dermatol, 1986; 122: 52.
17. Cherry GW, Hughes MA, Kingsworth AN, et al. Oxford textbook of surgery. Section 1. Wound healing. Oxford university press. 1995; p3.
18. Morovic CG. The use of hydrocolloid dressings on burn patients.Helios,1996; 2: 7.
19. Wilhelmsen F. Treatment of pressure sores with hydrocolloid dressings-a review of two clinical studies. The first joint meeting of the Chinese Tissue Repair Society and the European Tissue Repair Society. 1996;p36.
20. Bull RH, Leigh IM. Alginate dressings for exudating leg ulcer: a randomized study of comfeel: alginate dressing VS kaltostat.5~(th) Annual meeting of the European Tissue Repair Society. 1995; p174.
21 Bolton L,Monte K,Pirone L.Occlusion and wound healing. 2~(nd) joint meeting of the wound healing Society and the European Tissue Repair Society. 1996; p118.
22. Arville K(eds).Wound Care Manual.Australia,Encore Productions, 1995;120.
1. Langaker MT, Harrison MR, Langaker JC. J Pediatr Surg, 1989; 124(8): 793-798.
2. Krummel TM, Nelson JM, Dteglmann RF. J Pediatr Surg, 1987; 22(7): 640-644.
3. Broker BJ, Reiter D. OtolaryngoI Head Neck Surg, 1994; 110(6): 547-549.
4. Mast BA, DlegeInlann RF, KrummeI TM. Surg Gynecol Obstet, 1992; 174(5): 441-451.
5. DestaI GH, Gamelli RL. Surg Gynecol Obstet, 1993; 176(3): 299-306.
6. Frantz Fw, Bettinger DA, Haynes JH. J Pediatr Surg, 1993; 28(3): 428-434.
7. Adzick NS, Longaker MT. Ann Surg, 1992; 215(1): 3-7.
8. Jonsson K, Jensen JA, Goodson WH, et al. Ann Surg, 1991; 214(5): 605-613.
9. Frantz FW, Dlegelmann RF, Mast BA. J Pediatr Surg, 1992; 127(8): 945-949.
10. Grimwood RE, Baskin JB, Nielsen LD, et al. J Invest Dermat, 1988; 90(4): 434-440.
11. Longaker MT, Ernie S, Chiu BS, et al. Ann Surg, 1991; 213(4): 292296.
12. Estes JM, Adzick NS, Harrison MR. J Pediatr Surg, 1993; 28(10): 1227-1231.
13. Longaker MT, Adzick NS, Hall JL. J Pediatr Surg, 1990; 25(4): 430-433.
14. Lin RY, Sullivan KM, Argenta PA. Et al. Ann Surg, 1995; 222(2): 146-154.
15. Sporn MB, Roberts AB. J Cell Biol, 1992; 119(5): 1017～1021.
16. Shah M, Foreman DM, Ferguson MWJ. J Cell Sci, 1994; 107(5): 1137-1157.
17. Adzick NS, lorenz HP. Ann Surg, 1994; 220(1): 10.
18. Olutoye DO, Yager DR, Cohen IK et al. J Pediatr Surg, 1996; 31(1): 91-95.
19. Adolph VR, Dlsanto SK, Bleacher JC. J Rediatr Surg, 1993; 28(10): 1316-1320.
20. Longaker MT, Whitby DJ, Mast WJ. et al. Ann Surg, 1994; 219(1): 65-72.
21. Andrew DR, Longaker MT, Adzick NS. J Pediatr Surg, 1990; 25(8): 898-901.
22. Sullivan KM, Meuli M, Macgillivray TE. Surgery, 1995; 118(1): 82-86.
(本文发表与《国外医学》创伤与外科基本问题分册，1997；18(1)：9-12．)
2. Eveline B. W. The role of growth factors in wound healing. Skin Pharmacy, 1991; 4: 175-182.
3. Sporn L. B. and Roberts A. B. Introduction: What is TGF-β? wiley, chichester (Ciba Foundation symposium 157), 1991; 1-6.
4. Beck S, DeGuzman L, Lee WP, et al. One systemic administration of TGF-β_1 reverses age or glucocorticoid impaired wound healing. J Clin Inverst, 1993; 92: 2841-2849.
5. Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound healing: single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest, 1989; 84: 640-646.
6. Herndon DN, Barrow RE, Kunkel KE, et al. Effects of recombinant human growth hormone on donor site healing in severely burned children. Ann Surg. 1990 212: 424-431.
7. Gilpin DA, Barrow RE, Rutan RL, et al. Recombinant human growth hormone accelerates wound healing in children with large cutaneous burns. Ann Surg, 1994; 220: 19-24.
8. Hatz RA, Niedner R. Vanscheidr W. et al. Wound healing and wound management. Springer-verlag Berlin Heidelberg, 1994: 151.
9. Flanga M, Growth factors and wound healing. Wound Healing, 1993; 11: 667-675.
10. Davidson JM, Broadley KN. Quaglino D. Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor-β_1 therapy. Wound Rep Reg, 1997; 5: 77-88.
11. Massague J. The transforming growth factor beta family. Ann Rev Cell Biol, 1990; 6: 597-642.
12. Barnard JA, Lyons RM and Moses HL. The cell biology of transforming growth factor β Biophys. Acat, 1990; 1032: 79-87.
13．周延冲，马贤凯．唐佩弦等．多肽生长因子基础与临床．北京．中国科学技术出版 社.1992年第一版;P234.
14. DERYNCK R, Jarrett JA, Chen EY. et al. Human transforming growth factor-beta CDNA sequence and expression in tumor cell lines. Nature, 1985; 316: 701-705.
15. Masui, T. Wekefield, L.M lechner J.E. Type beta transforming growth factor is the primany differentiation-inducing serum factor for normal human bronchial epithelial cells.Proc Natl Acad Sci USA, 1986; 83: 2438-2442.
16. Moses HL. Tucker R.F. Leof E.B. et al. type beta transforming growth factor is a growth stimulator and a growth inhibitor. Cancer Cells (cold spring Harber), 1985; 3: 65-71.
17. Tucker RF, Shipley GD, Moses HL. Growth inhibitor from BSC-1 cells closely related to platelet type beta transforming growth factor. Science, 1984; 226: 705-707.
18. Frater-Schroder M. Muller G., Birchmeier W. et al. Transforming growth factor-β inhibits endothelial cell proliferation. Biochem Biophys Res Commun. 1986; 137: 295-302.
19. Whal SM, Hunt DA, Wakefield LM. Transforming growth factor-β induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sic USA, 1987; 84: 5788-5792.
20. Buckley-sturrock A, Wood W, Senior RM, et al. Differential stimulation of collagenase and chemotactic activity in fibroblasts derived from root wound repair tissue and human skin growth foctors. J Cell Physical. 1989: 138: 70-78.
21. Postlethwaite AE, Keski-Oja J, Moses HL, et al. Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta. J Exp Med, 1987:165: 251-256.
22. Roberts AB, Heine UI, Flanders KC, et al. Transforming growth factor β. In:Fleischmajer R, olsen BR, kiihn k(eds). Smuture. Molecular Biology, and pathology of collagen. Ann NY, Acad Sci, 1990; 580: 225-232.
23. Roherts AB, Sporn MB, Assoian PK, et al. Transforming growth factor type-beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA, 1986; 83: 4167-4171.
24. Peltonen J, Kahari L, Jaakkola S, et al. Evaluation of transforming growth factor β(TGF-β) and type I procollagen gene expression in fibrotic skin diseases by in situ hybridization. J Invest Dermatol, 1990; 94: 365-371.
25. Gruschwitz M, Miiller PK, Sepp N, et al. Transcription and expression of transforming growth factor type beta in the skin of progressive systemic sclerosis: a mediator of fibrosis? J Invest Dermatol, 1990; 94: 197-203.
26. Massague J. Receptors for the TGFβ family. Cell, 1992; 69: 1067-1070.
27. Wolff JA, Malone RW, Williams P, et al. Direct gene transfer into mouse muscle in vivo Science, 1990; 247: 1465-1468.
28. Wolff JA, Ludtke JJ. Acsadi G, et al. A long-term persistence of plasmid DNA and foreign gene expression in mouse muscle. Hum Mol Genet, 1993; 1: 363-369.
29. Wolff JA, Dowty ME, Jiao S, et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J Cell Science, 1992; 103: 1249-1259.
30. Sikes ML, O'malley BW, Finegold MJ, et al. In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum Gene Ther, 1994; 5: 837-844.
31. Meyer KB. Intratracheoal gene delivery to the mouse airway: Characterization of plasmid DNA expression and pharmacokinetics. Gene Therapy, 1995; 2: 450-460.
32. Evans CH, Rodins PD. Gene therapy for arthritis, In: Wolff JA (ed). Gene Therapeutics. Methods and Applications of direct Gene Transfer. Birkhauser: Boston. 1994: 320-343.
33. Schwartz B, Benoistc, Abdallah B, et al. Gene transfer by naked DNA into adult mouse brain Gene Therapy, 1996; 3: 405-411.
34. Takehara T, Hayashi N, Yamamoto M, et al. In vivo gene transfer and expression in rat stomach by submucosal injection of plasmid DNA. Hum. Gene Ther, 1996; 7: 589-593.
35. Budker V, Zhang G, Knechtle S, et al. Naked DNA delivered introportally expresses efficiently in hepatocytes. Gene Therapy, 1996; 3: 593-598.
36. Dankol, Wolff JA. Direct gene transfer into muscle. Vaccine, 1994; 12: 1499-1502.
37. Ulmer JB, Peck RR, Dewitt CM, et al. Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines. Vaccine. 1994; 12: 1541-1544.
38. Davis HL, Michel ML, Mancini M, et al. Direct gene transfer in skeletal muscle: plasmid DNA-based immunization against the hepatitis B virus surface antigen. Vaccine, 1994: 12: 1503-1509.
39. Morgan RA, Walker R. Gene therapy for AIDS using retroviral mediated gene transfor to deliver HIV-1 antisense TAR and transdominant rev protein genes to syngeneeic lymphocytes in HIV-1 infected identical twins. Hum Gene Ther, 1996; 7: 1281-1206.
40. Qin HX, Chatterjee SK. Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF. Hum gene Ther, 1996; 7: 1858-1860.
41. Sugary S, Fujitak, Kikuchi A, et al. Inhibition of tumor growth by direct intratumoral gene transfer of herpes simplex virus thymidine kinase gene with DNA-Liposome complexes. Hum Gene Ther, 1996; 7: 223-230.
42．Younai S．Venters G．vu S．et al．全军防原医学研究作会：防原医学科研资料选编：军事医学科学院一所：放射性复合烧伤的实验(1)．1974：p196-207．
43．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社．1996年第一版；p1-2．
44. Dtagert M, Ehrlich SD. Prolonged incubation in calcium chloride improves the competence of Escherichia Coli cells. Gene, 1979; 6: 23-27.
45. Cohen SN. Chang ACY, Hsu L. Nonchromosmal antibiotic resistance in bacteria: Genetic transformation of Escherchia Coli by R- factor DNA. Proc Natl Acad Sci USA. 1972; 62: 2110-2114.
46. Birnbiom HC, Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res, 1979; 7: 1513-1517.
47. Ish-Horowicz D, Burke JF. Rapid and efficient cosmid cloning. Nucleic Acids Res, 1981; 9: 2989-2994.
48. Sugio K, Ishida T, Yokiyama H, et al. Ras gene mutations as a prognostic markers in adenocarcinoma of the human lung without lymph node metastasis. Cancer Res, 1992; 52 2903-2906.
49．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社．1996年第一版；P19．
50. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning. A Laboratory Manual., 2nd, eds, Cold Spring Harbor Laboratory. Press, Cold Spring Harbor, New York. 1989: P1.38-1.39
51．彭秀玲，袁汉英．基因工程实验技术．长沙．湖南科学技术出版社．1987年第一版：P48-59．
52．龙建银，张宏权，王会信．人转化生长因子β1 cDNA在哺乳动物细胞中表达的研究．第一届多肽生长因子基础与临床研讨会论文摘要．1994：10：31-33．
53. Andersson S, Davis DN, Dahlback H, et al. Cloning, structure, and expression of the mitochondrial cytochrome P-450 sterol 26-hydroxylase, a bile acid biosynthetic enzyme. J Biol Chem, 1989; 264: 8222-8229.
54. Kohn DB. The current status of gene therapy using hematopoietic stem cells. Curr Clin Pediatr, 1995; 7: 56-63.
55. Kotin RM. Prospects for the use of adeno-associated virus as a vector for human gene therapy. Hum Gene Ther, 1994; 5: 793-801.
56. Boris-Lawrie K, Temin HM. The retroviral vector. Replication cycle and safety considerations for retrovirus-mediated gene therapy. Ann Necl Acad Sci, 1994; 716: 59-70.
57. Yang Y, Li Q, Ertl HCJ, et al. Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol. 1994; 69: 2004-3015.
58. Smith C. Retrooiral vector-mediated gene transfer into hematopoietic cells: Prospects and issues, J Hematother, 1992; 1: 155-166.
59. Rosenfield MA, Ronald G, Crystal RG. Gene therapy for pulmonary diseases. Pathol Biol, 1993; 41: 677-680.
60. Halbert CL, Alexander IE, Wolgamot GM, et al. Adeno-associated virus vectors transduce primary cells much less efficiently than immortalized cells. J Virol, 1995, 69: 1473-1479.
61. Glorioso JC. Goins WF, Fink DJ, et al. Herpes simplex virus vectors and gene transfer to the brain. Dev Biol Stand, 1994; 82: 79-87.
62. Goldman MJ, Litzky LA, Engelhardt JF, et al. Transfer of the CFTR gene to the lung of nonhuman primates with El-deleted, E2-defective recombinant adenoviruses: a preclinical toxicology study. Hum Gene Ther, 1995; 6: 839-851.
63. Murphy E. Gene therapy's growing pains. Science, 1995; 269: 1052-1053.
64. Vile RG, Russell SJ. Retroviruses as vectors. Br Med Bull, 1995; 51: 12-30.
65. Strayer DS. Milano J. SV40 mediates stable gene transfer in vivo. Gene Therapy, 1996: 3: 581-587.
66．卢圣栋主编．现代分子生物学实验技术．北京．高等教育出版社．1993年第一版：P277．
67．Sambrook J．Fritsch EF．Maniatis T．(金冬雁，黎孟枫译)分子克隆实验指南．北京．科学出版社．1992年第二版；p474-479．
68．SambrookJ，Fritsch EF，Maniatis T．(金冬雁，黎孟枫译)分子克隆实验指南．北京．科学出版社．1992年第二版；p463-469．
69．林万明主编．临床基因探针诊断实验技术．上海．上海科学技术出版社．1993年第一版；p17-18．
70．林万明主编．PCR技术操作和应用指南．北京．人民军医出版社．1993年第一版：p28-56．
71．高亚兵，熊兰琦，赵波等．几种修复P53蛋白抗原免疫组化方法的比较．解放军医学杂志，1995：20：461-462．
72．苏慧慈：质粒杂交．北京冲国科学技术出版社．1994年第一版；p59-229．
73．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社．1996年，第一版：P128-141．
74. Michalski JP. A modified double antibody sandwich enzyme-linked immunosorbent assay for measurement of alphal-antitrypsin in biologic fluid. J Immun met, 1985: 83: 101-112.
75．龚志锦，詹容洲．病理组织制片和染色技术．上海．上海科学技术出版社．1994第一版；P48-52．
76．龚志锦，詹容洲．病理组织制片和染色技术．上海．上海科学技术出版社．1994 第一版；P271．
77．黎鳌主编．烧伤治疗学．第2版．北京．人民卫生出版社，1995，p18-24．
78. Peacock EE: Wound repair, Philadelphia W. B Saunders, 1984.
79．张乐鸣．伤口愈合的现代概念．《国外医学》创伤与外科基本问题分册，1987；3：129-132．
80. Hunt TK. Basic principles of wound healing. J Trauma, 1990; 30(12 Suppl): s122-128.
81. Clark RA. Growth factors and wound repair. J Cell Bioch, 1991; 46: 1-2.
82. Kingsnorth AN and Slavin J. Peptide growth factors and wound healing. Br J Surg, 1991; 78: 1286-1290.
83. Logan A, Berry M, Gonzalez AM, et al. Effects of transforming growth factor β1 on scar production in the injured central nervous system of the rat. Eur. J Nouros, 1994; 6: 355-363.
84. Younai S, Venters G, Vus, et al. Role of growth factors in scar contraction: an in vitro analysis. Ann Plast Surg, 1996; 36: 495-501.
85. Assoian Rk: The role of growth factors in tissue repair Ⅳ: Type beta transforming growth factor and stimulation of fibrosis. In the molecular and cellular, Biology of Wound Repair, edited by clark RAF, Henson PM. P273, New York, Plenum Press. 1988.
86. Hatz RA, Niedner R, Vanscheidt W, et al (eds). Wound Healing and Wound Management. Springer-Verlag Berlin Heidelberg, 1994; 1-11.
87. Brown GL, Curtsinger LJ, White M, et al. Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann Surg, 1988; 208: 788.
88. Drorak HK. Tumor: Wound do not heal. N Engl J Meal, 1986; 315: 1650-1659.
89. Sporn MB, Roberts AB, Eds. Peptide growth factors and their receptors Ⅰ Berlin: Springer-verlag, 1990; 419-472.
90. Muller G. Inhibitory actin of transforming growth factor-β on endothelial cells. Proc Natl Acad Sci USA, 1987; 84: 5600-5604.
91. Sporn MB, Roberts Ab, Wakefield LM, et al. Transforming growth factor-β biological function and chemical structure. Science, 1986; 233: 532-534.
92. Scott PG, Ghahary A, Chambers MM, et al. Biological basis of hypertrophic scarring. In: Advances in structural biology. Greenwich, CT: JAI Press, 1994; 3: 157-201.
93. Deitch EA, Wheelahan TM, Rose MP. Hypertrophic burn scars: analysis of variables. J trauma, 1983; 23: 895-899.
94. Roberts AB, Sporn MB, Handbook of experimental peptide growth pharmacology. Factors and their receptors. Heidelberg: Springer-Verlag. Berlin, 1990; 7-8.
95. Scott PG, Ghahary A, Chambers MM. et al. Biological basis of hypertrophic scarring,In: Advances in structural biology Vol3 JAI press Inc. Greenwich, Connecticut, 1994;157-201.
96. Evelime BW. The role of growth factors in wound healing, Skin pharmacol, 1991; 4:175-182.
97. Ignotz RA. Transforming growth factor beta stimulates the expression of fibronectin and collagen and their incorporation into the extracelluar matrix. J Biol Chem, 1986; 261:4337-4345.
98. Overall CM, Wrana JL, Sodek J. Independent regulation of collagenase, 72KD-progelatinase, and metalloendoprotinase inhibitor(TIMP) expression in human fibroblasts by transforming growth factor-β. J Biol chem, 1989; 264: 1860-1869.
99. Fieyel VD, Knighton DR. Transforming growth factor-beta causes indirect angiogenesis by recruiting monocytes. FASEB (Fed Am Soc Exp Biol) J 2:A.1601(Abstr). 1994.
100. Montesano R, Orci L. Transforming growth factor -β stimulated collagen matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci USA,1988; 85: 4894-4897.
101. Desmouliere A, Geinoz A. Gabbiani F, et al. Transforming growth factor -β induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing fibroblasts. J Cell Bilo, 1993; 103-111.
102. Ehrlich HP. The role of nonnective tissue matrix in wound and fracture healing. In: Barbul A, et al. Eds. Growth factors and other aspects of wound healing. New York:Liss, 1988: 243-258.
103. Logan A, Berry M, Gonzalez AM, et al. Effects of transforming growth factor-β_1 on scar production in the injured central nervous system of the rat. Eur J Neuro, 1994; 6: 355-363.
104. Shah M, Foreman DM, Ferguson MWJ. Control of scarring in adult wounds by neutralizing antibody to transforming growth factor-β. Lancet, 1992; 339: 213-214.
105. Schodel F, Aguado MT, Lambert PH. Introduction: Nucleic acid vaccines, WHO. Geneva. Vaccine, 1994; 12: 1491-1492.
106. Robinson HL, Hunt LA, Webster RG. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine, 1993; 11: 957-960.
107. Stratford-perricaudet LD, Maken I, Perricandet M et al. Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest, 1992; 90: 626-630.
108. Wolff JA, Dowty ME, Jiao S, et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T- tubules and calveolae of mammalian skeleted muscle. J Cell Sci, 1993; 103: 1249-1259.
109. Smith KT, Shepherd AJ. Boyd JE, et al. Gene delivery systems for use in gene therapy: an overview of quality assurance and safety issues. Gene Therapy, 1996; 3: 190-250.
110. Wolff JA, Ludthe JJ, Acsadi G, et al. A long-term persistenceof plasmid DNA and foreign gene expression on mouse muscle. Hum Mol Genet, 1992; 1: 363-369.
111．黎鳌主编．烧伤治疗学．第2版．北京．人民卫生出版社，1995：p538-540．
112．张涤生，李青峰．我国整形外科现状与二十一世纪展望．中华整形烧伤外科杂志．1997；1-4．
113. Cornell K, Waters DJ. Impaired wound healing in the cancer patient: effects of cytotoxic therpy and pharmacologic modulation by growth factors. Vet Clin North Am Small Anim Pract, 1995; 25: 111-131.
114. Border WA, Okuda S, Languino LR, et al. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor-β_1 Nature, 1990; 346: 371-374.
115．张树欣．肌成纤维细胞与疤痕组织．中华整形烧伤外科杂志．1987；3：229-232．
116．宋维铭，管正玉，孙广慈等．体外观察维甲类药物对人体皮肤成纤维细胞的抑制作用．中华整形烧伤外科杂志，1992；8：218-220．
117．高庆新，吴文祥，张涤生等．疤痕成纤维细胞培养和生长动力学的研究．中华整形烧伤外科杂志，1993；9：379-382．
118. Diegelmann RF, Cohen IK, McCoy BJ. Growth kinetics and collagen synthesis of normal skin, normal scar, and keloid fibroblasts in vitro. J Cell Physiol, 1979; 98: 341.
119. Russell JP, Witt WS. Cell size and growth characteristics of cultured fibroblasts isolated from normal and keloid tissues. Plast Reconstr Surg, 1976; 57: 207.
120. Russell SB, Trupin KM, Rodriguez-Eatons et al. Reduced growth factor requirements of keloid derived fibrroblasts may account for tumor growth. Proc, Natl Acad Sci USA, 1988; 85: 587.
121. Cohen IK, Beaven MA, Horakova A, et al. Histamine and collagen synthesis in keloid and hypertrophic scar. Surg forum, 1972; 23: 509.
122．姜泊，张亚历月殿元．分子生物学常实验方法．北京．人民军医出版社，1996年第一版．p157-161．
123. Felgner PL, Gadek TR, Helm M, et al. Lipofection: A highly efficient, lipid mediated DNA-transfection procedure. Proc Natl Acad Sci USA, 1987; 84: 7413.
124．司徒镇强．吴军正主编．细胞培养．陕西．世界图书出版公司．1996年第一版．p186-187．
125．司徒镇强，吴军正主编．细胞培养．陕西．世界图书出版公司，1996年第一版，p183-185．
126. Tuker RF, Shipley GD, Moses HL, et al. Growth inhibitor from BSC-1 cells is closely related to the platelet type β transforming growth factor. Science, 1984; 226: 705-707.
127. Keski-Oja J, Lyons RM, Moses HL. Immunodetection and modulation of cellular growth with antibodies against native transforming growth factor-β. Cancer Res, 1987: 47: 6451-6458.
128. Arteaga CL, Coffey RJ, Ougger TC, et al. Growth stimulation of human breast cancer cells with antitransforming growth factor β. Cell Growth & Differ, 1990; 1: 367-374.
129. Hafez MM, Infante D, Winawer S, et al. Transforming growth factor β acts as an autocrine-negative growth regulator in colon enterocytic differentiation but not in goblet cell maturation. Cell growth & Differ, 1990; 1: 617-626.
130．李英春．重组人α-干扰素瘢痕成纤维细胞生物学作用的研究．第四军医大学硕士学位论文，1996；p25-34．
131. Roberts AB, Flanders KC, Kondaiah P. et al. Transforming growth factor beta: biochemistry and roles in embryogenesis, tissue repair and remodeling; and carcinogenesis. Recent prog Horm Res, 1988; 44: 157-197.
132. Roberts AB, Sporn MB, Assoian RK, et al. Transforming growth factor type beta: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA, 1986; 83: 4167-4171.
133. Wahl SM, Hunt DA, Wakefield LM, et al. Transforming growth factor type beta induces monocyte chemotaxis and growth factor production. Proc Natl Acad Sci USA, 1987; 84: 5788-5792.
134．汪良能，高学书主编．整形外科学．北京．人民卫生出版社，1989：p318-320．
135. Gaston P. Quaba AR. The pulsed tuneable dye laser as an aid in the management of postbum scarring. Burns, 1996; 22: 203-205.
136．黎鳌主编．烧伤治疗学．第二版．北京．人民卫生出版社，1995；p538-545．
137. Lee SM. Ngim CK, Chan YY, et al. A comparison of sil-k and epiderm in scar management. Bums, 1996; 22: 483-487.
138. Gabiani G. Granulation tissue as a contractile organ: A study of structure and function. J Exp Med, 1972; 135: 719.
139．李永林．瘢痕挛缩机理的研究和生物学治疗进展，《国外医学》创伤与外科基本问题分册．1997：18：7-9．
140．贾赤宇．张键．胚胎无瘢痕愈合的研究进展．《国外医学》创伤与外科基本问题分册．1997；18：9-12．
141．扬松林，何清濂，林子豪等．瘢痕成纤维细胞三维培养的实验研究冲华整形烧伤外科杂志，1996；12：2-5．
142. Sahara K, Kucukcelebi A, Francis KO, et al. Suppression of in vitro proliferative scar fibroblast contraction by interferon alfa-2b. Wound Rep Reg, 1993; 1: 22-27.
143. Choi BM, Kwak HJ, Jun CD, et al. Control of scarring in adult wounds using antisense transforming growth factor β_1 oligodeoxynucleotides. Immun Cell Biol, 1996; 74: 144-150.
144. Schurch W, Seemayer TA, Gabbiani G. Myofibroblast. In: Sternberg SS, editor. Histology for pathologister. New York, Raven Press, 1992: 109-144.
145. Janssen H, Rooman R and Robertson JIS. Wound Healing, UK, wrightson Biomedical Bublishing 1td, 1991; 103-115.
146．姜泊，张亚历，周殿元．分子生物学常用实验方法．北京．人民军医出版社，1996：p152．
147．杨建涛，吴曼．哺乳动物细胞的基因转染．《国外医学》分子生物学分册，1987：9：106-110．
148. Bascom CC, Wolfshohl JR, Coffey RJ, et al. Complex regulation of transforming growth factor β1 β2 and β3 mRNA expression in mouse fibroblasts Keratinocytes by transforming growth factor β1 and β2. Mol Cell Biol, 1989; 9: 5508-5515.
149. Schwarz LC, Wright JA, Gingras MC, et al. Aberrant TGFβ production and regulation in metastatic malignancy. Growth factors, 1990; 3: 115-127.
150. Coffin JM. Molecular mechanisms of nucleic acid integration. J Med, Vivo, 1990; 31: 43-49.
151. Massagne J. The transforming growth factor beta family Ann. Rev Cell Biol. 1990; 6: 597-642.
152. Moses HL, Tucker RF, Leof EB, et al. Type β transforming growth factor is a growth stimulator and a growth inhibitor. Cancer Cells, 1985; 3: 65-71.
153. Cochrane CA, Freeman KL, Knottenbelt DC, et al. Effect of growth factors on the characteristics of cells associated with equine wound healing and sarcoid formation. Wound Rep Reg, 1996; 4: 58-65.
154. Roberts AB, Anzano MA, Wakefield LM, et al. Type β transforming growth factor: A bifunctional regulator of cellular growth. Proc Natl Acd Sci, USA, 1985; 82: 119-123.
1．程天民主编．创伤战伤病理学．第11版．北京．解放军出版社，1992；28-29．
2. Rockwell WB, Cohen IK, Fhrlich HP. Keloids and hypertrophic scars: a comprehensive review. Plast Reconstr Surg, 1989; 84: 827-831.
3. Holtz G. Prevention and management of peritoneal adhesions. Fertil steril, 1984; 41: 496-507.
4. Sahara K, Kucukcelebi A, Francis KO, et al. Suppression of in vitro proliferative scar fibroblast contraction by interferon alfa-2b. Wound Rep Reg, 1993; 1: 22-27.
5. Falanga A, Grinnel F, Gilchrest B, et al. Experimental approaches to chronic wounds. Wound Rep Reg, 1995; 3: 132-140.
6. Browse N. The pathogenesis of venous ulceration. J Vasc Surg, 1988; 7: 468-672.
7. Falang V. Chronic wounds: Pathophysiologic and experimental considerations. J Invest Dermatal, 1993; 100: 721-725.
8. Falanga V, Grinnell F, Gilehrest B, et al. Workshop on the pathogenesis of chronic wounds. J Invest Dermatol, 1994; 102: 125-127.
9. Kirsner RS, Eaglstein WH. The wound healing process. Dermatol Clin, 1993; 11: 629-640.
10. Hammar. H. Wound healing. Int J Dermatol, 1993; 32: 6-15.
11. Clark RAF. Cutaneous wound repair: Molecular and cellular controls. Drog Dermatol, 1988; 22: 1-12.
12. Sempowski GD, Borrello MA, Blieden TM, et al. Fibroblast heterogeneity in the healing wound. Wound Rep Reg, 1995; 3: 120-131.
13. Tredget EE. The molecular biology of fibroproliferative disorders of the skin: Potential cytokine therapeutics. Ann Plast Surg, 1994; 33: 152-154.
14. Cherry GW. The past present and future of wound healing. Wound Rep Reg, 1995; 3: 119.
15．张乐鸣．伤口愈合的现代概念．《国外医学》创伤与外科基本问题分册，1987；3：129-132．
16. Hunt TK. Basic principles of wound healing. J Trauma, 1990; 30: (12 Suppl): s122-128.
17. Orgill D, Demling Rh. Current concepts and approaches to wound healing. Crit Care Med, 1988; 16: 899-907.
18. Schilling JA. Wound healing. Surg Clin North Am, 1976; 56: 869-874.
19. Sporn MB, Roberts AB, Eds. Peptide growth factors and their receptors Ⅱ. Berlin: Springer-Vedag, 1990; 511-524.
20. Reibman J, Meixler S, Lee TC, et al. Transforming growth factor-β_1, a potent chemoattractant for human neutrophils, bypasses classic signal transduction pathways. Proc Natl Acad Sci USA, 1991; 88: 6805-6809.
21. Cromack DT. Current concepts in wound healing: growth factor and macrophage interaction. J Trauma 1990; 30(12 Suppl): s129-133.
22. Leirisalo-Repo M. The present knowledge of the inflammatory process and inflammatory mediators. Pharmacol Toxicol, 1994; 75: 1-3.
23. Liebovich SJ, Ross R. A macrophage-dependent factor that stimulates the proliferation of fibroblasts in vitro. Am J Pathol, 1976; 84: 501-504.
24. Igarashi A, Okochi H, Bradham DM, et al. Regulation of connective tissue growth factor gene expression in human skin fibroblasts and curing wound repair. Mol Biol Cell, 1993; 4: 637-645.
25. Wahl SM. Transforming growth factor beta (TGF-β) in inflammation; a cause and a cure. J Clin Immunol, 1992; 12: 61-74.
26. Tarauzzer RW, Schultz GS. Biochemical analysis of acute and chronic wound environments. Wound Rep Reg, 1996; 4: 321-325.
27. Longaker MT, Bouhana KS, Harrison MR, et al. Wound healing in the fetus. Wound Rep Reg, 1994; 2: 104-112.
28. Dover R, Wright NA. The cell proliferation kinetics of the epidermis. In: Goldsmith LA(ed) physiology, Biochemistry, and Molecular Biology of the skin. New York: Oxford University Bess, 1991; 239-256.
29. Larson DL, Abstons, Dobrkovsky M, et al. The prevention and correction of burn scar contracture and hypertrophy. Galveston: Shriners Burns Institute, 1973; 1-21.
30. Kloth IC, Miller KH, The inflammatory response to wounding. In: Kloth IC, McCulloch JM, Feedar JA(eds) Wound Healing: alternatives in management, Philadelphia: FA Davis, 1990; 3-13.
31. Linares HA. From wound to scar. Burns, 1996; 22: 339-352.
32. Gabbiani G, Hirschel BJ, Ryan GB, et al. Granulation tissue as a contractile organ. A study of structure and function. J Exp Med, 1972;135: 719-734.
33. Ehrlich HP. Wound closure: Evidence of cooperation between fibroblasts and collagen matrix. Eye, 1988; 2: 149-157.
34. Olutoye OO, Cohen K. Fetal wound healing: An overview. Wound Rep Reg, 1996; 4: 66-74.
35. Roberts AB. Anzano MH, Lamb LC, et al. New class of transforming growth factors potentiated by epidermal growth factor. Proc Natl Acad Sci USA, 1981; 78: 5339-5343.
36. Allen JB, Manthey CL, Hand AR, et al. Rapid onset synovial inflammation and hyperplasia induced by TGFβ. J Exp Med, 1990; 171:231-247.
37. Fava RA, Olsen NJ, Postlethwaite AE, et al. TGFβ_1-induced neutrophil recruitment to synovial tissues: implications for TGFβ-driven synovial inflammation and hyperplasia. J Exp Med, 1991; 173: 1121-1132.
38. Postlethwaite AE, Keski-oja J, Mosses HL, et al. Stimulation of the chemotactic migration of human fibroblasts by TGFβ. J Exp Med, 1987;165:251-256.
39. Reibman J, Meixler S, Lee TC, et al. Transforming growth factor β_1, a potent chemoattractant for human neutrophils, bypasses classic signal-transduction pathways. Proc Natl Acad Sci USA, 1991; 88: 6805-6809.
40. Adams DH, Hathaway DM, Shaw J, et al. Transforming growth factor-β induces T lymphocyte migration in vitro. J Immunol, 1991; 147: 609-612.
41. Koyama N, Koshikawa T, Morisaki N, et al. Bifunctional effects of transforming growth factor-β on migration of cultured rat aortic smooth muscle cells. Biochem Biophys Res Commun, 1990; 169: 725-729.
42. Massague J, Transforming growth factorβ family. Ann Rev Cell Biol,1990; 6: 597-641.
43. Rokerts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-β(TGF-β). Growth factors, 1993; 8: 1-9.
44. Mast BA, Schultz GS. Interactions of cytokines, growth factors and proteases in acute and chronic wounds. Wound Rep Reg, 1996; 4:411-420.
45. Roberts AB, Anzano MA, wakefield LM, et al. Type beta transforming growth factor: a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA, 1985; 82: 119-123.
46. Like B, Massague J: The antiproliferative effect of type beta transforming growth factor occurs at a level distal from receptors for growth-activating factors. J Biol Chem, 1986; 261: 13426-13429.
47. Shipley GD, Pittelkow MR, Wille JJ Jr, et al. Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res, 1986;46:2086-2071.
48. Fratter-schroder M, Muller G, Birchmeier W, et al. Transforming growth factor-β inhibits endothelial cell proliferation. Biochem Biophys Res Comman, 1986; 137: 295-302.
49. Hebda PA: Stimulatory effects of transforming growth factor-β and epidermal growth factor and epidermal cell outgrowth from porcine skin explant cultures. J Invest Dermatol, 1988; 91: 440-445.
50. Majack RA, Majesky MW, Goodman LV, Role of PDGF-A expression in the control of vascular smooth muscle cell growth by transforming growth factor-β. J Cell Biol, 1990; 111: 239-247.
51. Beck LS, Chen TL, Mikalanski P, et al. Recombinant human transforming growth factor-beta 1 (rhTGFβ_1) enhances healing and strength of granulation skin wounds. Growth Factors, 1990; 3: 267-275.
52. 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.
53. Mcmullen H, Longaker MT, Cabrera RC, et al. Spatial and temporal expression of transforming growth factor-β isoforms during ovine excisional and incisional wound repair. Wound Rep Reg, 1995; 3: 141-156.
54. Ellis I, Grey AM, Schor AM, et al. Antagonistic effects of TGFβ_1 and MSF on fibroblast migration and hyaluronic acid synthesis. J Cell Science, 1992; 102: 447-456.
55. Quaglino D, Nanney LB, Ditesheim JA, et al. Transforming growth factor beta stimulates wound healing and modulates extracellular matrix gene expression in pig skin: incisional wound model. J Invest Dermatol,1991; 97: 34-42.
56. Leiho M, Saksela O, Keski-Oja J. Transforming growth factor-β induction of type 1 plasminogen activator inhibitor. J Biol Chem, 1987;262: 17467-17474.
57. Brown GL, Curtsinger LJ, White M, et al. Acceleration of tensile strength of incisions treated with EGF and TGF-β_1. Ann Surg, 1988; 208:788-794.
58. Roberts AB, Sporn MB, Assoian RK, et al. Transforming growth factor type β: Rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci USA,1986; 83: 4167-4171.
59. Rong H, Tang XM, Zhao Y, et al. Postsurgical intraperitoneal exposure to glove powders modulates inflammatory and immune-related cytokine production. Wound Rep Reg, 1997; 5: 89-96.
60. Massague J, Boyd FT, Adres JL, et al. TGF-β receptors and TGF-β binding proteoglycans: recent progress in identifying their functional properties. Ann NY Acad Sci, 1990; 593: 59-72.
61. Border WA, Noble NA. Transforming growth factorβ in tissue fibrosis. New Engl J Med, 1993; 331: 1286-1292.
62. Masure S, Opdenakker G. Cytokine-mediated proteolysis in tissue remodeling. Experientia, 1989; 45: 542-549.
63. Jones KA, Kadonaga JT, Rosenfield PJ, et al. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell, 1987; 48: 79-89.
64. Short NJ. Regulation of transcription: are some controlling factors more equal than other? Nature, 1987; 236: 740-741.
65. Montesano R, Orchi L, Transforming growth factor beta stimulates collagen-matrix contraction by fibroblasts: implications for wound healing. Proc Natl Acad Sci USA, 1988; 85: 4894-4897.
66. Pierce GF, Berg JV, Rudolph R, et al. Platelet derived growth factor-BB and transforming growth factor beta-1 selectively modulate glycosaminoglycans, collagen, and myofibroblasts in excisional wounds. Am J Pathol, 1991; 138: 629-646.
67．付小兵，盛志勇．软组织创伤修复基础研究的现状与展望．解放军医学杂志，1997；22：12-13．
68. Stocum DL. Tissue restoration approaches and prospects. Wound Rep Reg, 1996; 4: 3-15.
69. Davidson JM, Broadley KN, Quaglino D. Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor-β_1 therapy. Wound Rep Reg, 1997; 5: 77-88.
70. Miller EJ, Gays. Collagen structure and function IN: Cohen IK, Diegelmann RF, Lindblad WJ, editors. Wound healing: biochemical and clinical aspects. Philadelphia: Saunders, 1992; 130-151.
71. Mast BA, The skin In: Cohen IK, Diegelmann RF, Lindblad WJ, editors Wound healing: biochemical and clinical aspects. Philadelphia: Saunders,1992; 344-355.
72. Rudolph R, VandeBerg J, Ehrlich HP. Wound contraction and scar contracture In: Cohen IK, Diegelmann RF, Lindblad WJ, editors. Wound healing: biochemical and clinical aspects Philadelphia: Saunders, 1992;177-194.
73. Merkel JR, Dipaolo BR, Hallok GG, et al. Type I and III collagen content of healing wounds in fetal and adult rats. Proc Soc Exp Biol Med,1988; 187: 493-497.
74. Lorenz HP, Chang J, Longaker MT, et al. Transforming growth factor beta 1 and 2 synergistically increase gene expression of collagen type I and III in fetal but not adult fibroblast. Surg Forum, 1993; 79: 723-725.
75. Whitby DJ, Ferguson MWJ. Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol, 1991; 147: 207-215.
76. Border WA, Ruoslahti E. Transforming growth factor-β in disease: the dark side of tissue repair. J Clin Invest, 1992; 90: 1-7.
77. Williams RS, Rossi AM, Chegini N, et al. Effect of transforming growth factorβ on postoperative adhesion formation and intact peritoneum. J Surg Res, 1992; 52: 65-70.
78. Logan A, Frautschy SA, Gonzalez AM, et al. Enhanced expression of transforming growth factorβ_1 in the rat brain after a localized cerebral injury. Brain Res, 1992; 587: 216-225.
79. Connor TB, Roberts AB, Sporn MB, et al. Correlation of fibrosis and transforming growth factor-β type 2 levels in the eye. J Clin Invest, 1989;83: 1661-1666.
80. Castilla, Prieto J, Fausto N. Transforming growth factors beta 1 and alpha in chronic liver disease: effects of interferon alfa therapy. N Engl Med, 1991; 324: 933-940.
81. Broekelmann TJ, Limper AH, Colby TV, et al. Transforming growth factor β_1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci USA, 1991; 88: 6642-6646.
82. Border Wa, Okuda S, Langnino, et al. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor β_1.Nature, 1990; 346: 371-374.
83. Peltonen J, Kahari L, Jaakkola S, et al. Evaluation of transforming growth factorβ and type I procollagen gene expression in fibrotic disease by in situ hybridization. J Invest Dermatol, 1990; 94: 365-371.
84. Steenfos HH. Growth factors and wound healing. Scand J Plast Reconstr Hand Surg, 1994; 28: 95-105.
85. Sullivan M, Lorenz HP, Meuli M, et al. A model of scarless human fetal wound repair is deficient in transforming growth factor beta. J Rediatr Surg, 1995; 30: 198-202.
86. Olutoge OO, Cohen K. Fetal wound healing. Wound Rep Reg, 1996; 4:66-74.
87. Krummel TM, Michna BA, Thomas BL, et al. TGFβ induces fibrosis in a fetal wound model. J Pediatr Surg, 1988; 23: 647-652.
88. Sullivan KM, Lorenz HP, Adzick NS. The role of transforming growth factor beta in human fetal wound healing. Surg Forum, 1993; 44: 625- 627.
89. Lorenz HP, Chang J, Longaker MT, et al. Transforming growth factor β_1 and β_2 synergistically increase collagen gene expression in fetal fibroblasts but not in adult fibroblasts. Surg Fornm, 1993; 44: 723-725.
90. Roberts AB, Sporn MB. Physiological actions and clinical applications of transforming growth factor-β (TGF-β). Growth factors, 1993; 8: 1-9.
91. Graycar JL, Miller DA, Arrick BA, et al. Human transforming growth factor-β_3: recombinant expression, and biological activities in comparison with transforming growth factor-β_1 and β_2. Mol Endocrinol,1989; 3: 1977-1986.
92. Cox DA. Transforming growth factor-beta 3. Cell Biol Int, 1995; 19:357-371.
93. Shah M, Foreman DM, Ferguson MWJ. Neutralization of TGFβ_1 and TGFβ_2 or exogenous addition of TGFβ_3 to cutaneous rat wounds reduces scarring. J Cell Sci, 1995; 108: 985-1102.
94. Shah M, Foreman DM, Ferguson MWJ. Neutralising antibody to TGF-betal,2 reduces cutaneous scarring in adult rodents. J Cell Sci, 1994; 107:1137-1157.
95. Serini G, Gabbiani G. Modulation of α-smooth muscle actin expression in fibroblasts by transforming growth factor-β isoforms: an in vivo and in vitro study. Wound Rep Reg, 1996; 4: 278-287.
96. Border WA, Nobel NA, Yammamoto T, et al. Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease. Nature, 1992; 360: 361-364.
97. Houghton PE, Keefer KA, Krummel TM. The role of transforming growth factor-β in the conversion from "scarless" healing to healing with scar formation. Wound Rep Reg, 1995; 3: 229-236.
1．汪美先主编．医学微生物学与免疫学．西安．陕西科学技术出版社，1989；p92-101．
2. Wolff JA, Malone RW, Willians P, et al. Direct gene transfer into mouse muscle in vivo Science, 1990; 247: 1465-1468.
3. Israel MA, Chan HW, Roroe WP, et al. Molecular cloning of polyoma virus DNA in Escherichia coli: plasmid vector system. Science, 1979; 203: 883-887.
4. Chan HW, Israel MA, Garon CF, et al. Molecular cloning of pdyoma virus DNA in Escherichia coli: lambda phage vector system. Science, 1979; 203: 887-892.
5. Schodel F, Aguado MT, Lambert PH. Introduction: nucleic acid vaccines, WHO, Geneva. Vaccine, 1994; 12: 1491-1492.
6. Lin H, Parmacek MS, Morle G, et al. Expression of recombinant genes in myocardium in vivo after direct injection of DNA. Circulation, 1990; 80: 2217-2221.
7. Acsadi G, Jiao S, Jani A, et al. Direct gene transfer and expression into rat heart in vivo. New Biol, 1991; 3: 71-81.
8. Sikes ML. O'malley BW, Finegold MJ, et al. In vivo gene transfer into rabbit thyroid follicular cells by direct DNA injection. Hum Gene Ther, 1994; 5: 837-844.
9. Malone RW, Hick man MA, Lehmann-Bruinsma K, et al. Dexamethasone enhancement of gene expression after direct hepatic DNA injection. J Biol Chem, 1994; 269: 29903-29907.
10. Yorandich J, O'malley B, Sikes M, et al. Gene transfer to synovial cells by intra-articular administration of plasmid DNA. Hum Gene Ther, 1995; 6: 603-610.
11. Schwartz B, Benoist C, Abdallab B, et al. Gene transfer by naked DNA into adult mouse brain. Gene Ther, 1996; 3: 405-411.
12. Raz E, Carson DA, Parker SE, et al. Intradermal gene immunication: The possible role of DNA uptake in the induction of cellular immunity to viruses. Proc Natl Acad Sci USA, 1994; 91: 9519-9523.
13．张灵生，汤健．脂质体作为基因载体的研究进展．《国外医学》分子生物学分册，1993；15：10-12．
14. Nabel EG, Gordon D, Yang ZY, et al. Gene transfer in vivo with DNA-liposome complexes: lack of autoimmunity and gonadal localization. Hum Gen Ther, 1992; 3: 649-656.
15. Davis HL, Demeneix BA, Quantion B, et al.. Plasmid DNA is superior to viral vectors for direct gene transfer in adult mouse skeletal muscle. Hum Gene Ther, 1993; 4: 733-740.
16. Stratford-Perricaudet LD, Maken I, Perricaudet M, et al, Widespread long-term gene transfer to mouse skeletal muscles and heart. J Clin Invest, 1992; 90: 626-630.
17. Wolff JA, Dowty ME, Jiao S, et al. Expression of naked plasmids by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscles. J Cell Sci, 1992; 103: 1249-1259.
18. Horwitz AF, Schotland DL. The Plasma membrane of the muscle fiber. In myology (Ed. Engel AE and Bawker BQ) New York: McGraw-Hill, p177-207.
19. Anderson RGW, Kamen BA, Rotherg KG, et al. Dotoeytosis: Sequestration and transport of small molecules by caveolae. Science, 11992; 255: 410-411.
20. Acsadi G, Jiao S, Jani A, et al. Direct gene transfer and expression into rat heat in vivo. New Biologist, 1991; 3: 71-81.
21. Whalen RG, Harris JB, Butler-Browne GS, et al. Expression of myosin isoforms during notexin-induced regeneration of rat soleus muscles. Dev Biol, 1990; 141: 24-40.
22. Davis HL, Whalen RG, Demeneix BA. Direct gene transfer into skeletal muscle in vivo factors affecting efficiency of transfer and stability of expression. Hum Gene Ther, 1993; 4: 151-159.
23. Yang MS, Burkholder J, Roberts B, et al. In vivo and in vitro gene transfer to mammalian somatic cells by particle bombardment. Proc Natl Acad. Sci. USA, 1990; 87: 5968-5972.
24. Williams RS, Johnston SA, Riedy M, et al. Introduction of foreign genes into tissue of living mice by DNA-coated microprojectiles. Proc Natl Acad Sci USA, 1991; 88: 2726-2730.
25. Zhou X, Berglund P, Rhodes G, et al. Self-replicating scmliki forest virus RNA as recombinant vaccine. Vaccine, 1994; 12: 1520-1514.
26. Ciernik IF, Krayenbuhl BH, Carbone DP. Puncture-mediated gene transfer to the skin. Hum Gen Ther, 1996; 7: 893-899.
27. Streilein JW. Skin-associated lymphoid tissue (SALT) origins and functions. J Invest Dermatol, 1983; 80: 12-16s.
28. Streilein JW. Skin-associated lymphoid tissue. In: Immune mechanisms in cutaneous disease (Ed. Norris DA) Marcel Dekker, New York and Basel, 1998; p73-96.
29. Robinson HL, Hunt LA, Webster RG. Protection against a lethal influenza virus challenge by immunization with a haemagglutinin-expressing plasmid DNA. Vaccine, 1993; 11: 957-960.
30. Fynan EF, Webster RG, Fuller DH, et al. DNA vaccines, protective immunization by parenteral, mucosal, and gene gun inoculations. Proc Natl Acad Sci USA, 1993; 90: 11478-11482.
31.Ulmer JB, Donnelly JJ, Parker SE, et al. Heterologous proteetion against inffuenza by injection of DNA encoding a viral protein. Science, 1993;259: 1745-1749.
32. Wang B, Ugen Ke, Srikantan V, et al. Gene inoculation generates immune responses against human immunoceficiency virus type I. Proce Natl Acad Sci USA, 1993; 90: 4156-4160.
33. Webster RG, Fynan EF, Santoro JC, et al. Protection of ferrets against influenza challenge with a DNA vaccine to the haemagglutinin. Vaccine,1994; 12: 1495-1498.
34. Budker V, Zhang G, Knechthe S, et al. Naked DNA delivered introportally expresses efficiently in hepatocytes. Gene Therapy, 1996; 3:593-598.
35. Lowrie DB, Tascon RE, Colston MJ, et al. Towards a DNA vaccine against tuberculosis. Vaccine, 1994; 12: 1537-1540.
36. Hoffman SI, Sedegah M, Hedstrom RC. Protection against malaria by immunization with a plasmodium yoelii circumsporozzoite protein nucleic acid vaccine. Vaccine, 1994; 12: 1529-1533.
37. Ulmer JB, Deck RR, Dewitt Cm, et al. Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines.Vaccine, 1994; 12: 1541-1544.
38. Evans Ch, Rooddins PD. Gene therapy for arthritis. In: Wolff JA(ed).Gene Therapeutics: Methods and Applications of direct gene transfer. Birkhauser: Boston, 1994; p320-343.
39. Qin HX, Chatterjee SK. Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF. Hum Gene Ther,1996; 7:1853-1860.
40. Morgan RA, Walker R. Gene therapy for AIDS, using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant rev protein genes to syngeneic lymphocytes in HIV-infected identical twins. Hum Gene Ther, 1996; 7: 1281-1306.
41. Jiao S, Williams P, Berg RK, et al. Direct gene transfer into non-human primate myofibers in vivo. Hum Gene Ther, 1992; 3: 21-33.
1. Leak CL. The old Egyptian papyri. University of Kansas Press, Lawrece,Kansas. 1952.
2. Adams F. The genuine works of hippocrates. The sydenham society,Lodon L849.
3. Gilje O. On taping (adhesive tape treatment) of leg ulcers. Acts Derm Vener, 1948; 28: 454.
4. Linsky CB, Roree DT, Dow T. Effects of dressings on wound inflammation and scar tissue. In: The surgical wound.(Dineen P and Hildick-Smith G,eds). Lea & Febiger,philadelphia 1981; 191.
5. Pirone L, Monte K, Shannon R, et al.. Wound healing under occlusion and non-occlusion in full- and partial-thickness wounds in swine.Wounds,1990;2:74.
6. Jostkleigrewe F, Brandt KA, Flechsig G, et al. Treatment of partial thickness burns of the hand with the preshaped, semipermeable procel burn cover: results of a multicentre study in the burn centers of Berlin,Duisburg and Munich. Burns, 1995; 2: 297.
7. Sedlarik KM, Vacik J, Wichterle O. Modern dressings. Hydrogels. Rozhl Chir, 1995; 74: 3.
8. Fuller FW, Parrish M, Nance FC. A review of the dosimetry of 27 silver sulfadiazine cream in burn wound treatment. J Bum Care Rehabi1,1995:15:213.
9 Constantine B, Monte K(eds). Burn debridement under occlusion. Proceedings American Burn Association, Las Vegas, March 1990.
10. Lydon MJ, Hutchinson JJ, Rippon M, et al. Dissolution of wound coagulum and promotion of granulation tissue under DuoDerm. Wounds,1989; 1:95.
11. Kneafsey B, Oshanghnessy M,Condon KC. The use of calcium alginate dressing in deep hand burns. Burns, 1996; 22: 40.
12. WinterGD. Formation of scab and rate of epithelialization of superficial wounds in the skin of the young domestic pig. Nature, 1962; 193:293.
13. Alrarez OM. The effect of occlusive dressings on collagen synthesis and re-epithelializatio in superficial wounds. J Surgical Research, 1983; 35:142.
14. Knighton DR, Silver IA, Hunt TK. Regulation of wound healing angiogenesis-effect of oxygen concentration. Surgery, 1981; 90: 262.
15. Cherry GW, Ryan TJ. Enhanced wound angiogenesis with a new hydrocolloid dressing. The Royal Society of Medicine,1995; 88: 61.
16. Varghese MC, Balin AK, Carter DM. Local environment of chronic wounds under synthetic dressings. Arch Dermatol, 1986; 122: 52.
17. Cherry GW, Hughes MA, Kingsworth AN, et al. Oxford textbook of surgery. Section 1. Wound healing. Oxford university press. 1995; p3.
18. Morovic CG. The use of hydrocolloid dressings on burn patients.Helios,1996; 2: 7.
19. Wilhelmsen F. Treatment of pressure sores with hydrocolloid dressings-a review of two clinical studies. The first joint meeting of the Chinese Tissue Repair Society and the European Tissue Repair Society. 1996;p36.
20. Bull RH, Leigh IM. Alginate dressings for exudating leg ulcer: a randomized study of comfeel: alginate dressing VS kaltostat.5~(th) Annual meeting of the European Tissue Repair Society. 1995; p174.
21 Bolton L,Monte K,Pirone L.Occlusion and wound healing. 2~(nd) joint meeting of the wound healing Society and the European Tissue Repair Society. 1996; p118.
22. Arville K(eds).Wound Care Manual.Australia,Encore Productions, 1995;120.
1. Langaker MT, Harrison MR, Langaker JC. J Pediatr Surg, 1989; 124(8): 793-798.
2. Krummel TM, Nelson JM, Dteglmann RF. J Pediatr Surg, 1987; 22(7): 640-644.
3. Broker BJ, Reiter D. OtolaryngoI Head Neck Surg, 1994; 110(6): 547-549.
4. Mast BA, DlegeInlann RF, KrummeI TM. Surg Gynecol Obstet, 1992; 174(5): 441-451.
5. DestaI GH, Gamelli RL. Surg Gynecol Obstet, 1993; 176(3): 299-306.
6. Frantz Fw, Bettinger DA, Haynes JH. J Pediatr Surg, 1993; 28(3): 428-434.
7. Adzick NS, Longaker MT. Ann Surg, 1992; 215(1): 3-7.
8. Jonsson K, Jensen JA, Goodson WH, et al. Ann Surg, 1991; 214(5): 605-613.
9. Frantz FW, Dlegelmann RF, Mast BA. J Pediatr Surg, 1992; 127(8): 945-949.
10. Grimwood RE, Baskin JB, Nielsen LD, et al. J Invest Dermat, 1988; 90(4): 434-440.
11. Longaker MT, Ernie S, Chiu BS, et al. Ann Surg, 1991; 213(4): 292296.
12. Estes JM, Adzick NS, Harrison MR. J Pediatr Surg, 1993; 28(10): 1227-1231.
13. Longaker MT, Adzick NS, Hall JL. J Pediatr Surg, 1990; 25(4): 430-433.
14. Lin RY, Sullivan KM, Argenta PA. Et al. Ann Surg, 1995; 222(2): 146-154.
15. Sporn MB, Roberts AB. J Cell Biol, 1992; 119(5): 1017～1021.
16. Shah M, Foreman DM, Ferguson MWJ. J Cell Sci, 1994; 107(5): 1137-1157.
17. Adzick NS, lorenz HP. Ann Surg, 1994; 220(1): 10.
18. Olutoye DO, Yager DR, Cohen IK et al. J Pediatr Surg, 1996; 31(1): 91-95.
19. Adolph VR, Dlsanto SK, Bleacher JC. J Rediatr Surg, 1993; 28(10): 1316-1320.
20. Longaker MT, Whitby DJ, Mast WJ. et al. Ann Surg, 1994; 219(1): 65-72.
21. Andrew DR, Longaker MT, Adzick NS. J Pediatr Surg, 1990; 25(8): 898-901.
22. Sullivan KM, Meuli M, Macgillivray TE. Surgery, 1995; 118(1): 82-86.
(本文发表与《国外医学》创伤与外科基本问题分册，1997；18(1)：9-12．)