Ⅳ期压疮愈合过程中创面渗出液基质金属蛋白酶-9、基质金属蛋白酶抑制剂-1的表达水平变化的研究
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摘要
目的探讨Ⅳ期压疮愈合过程中创面渗出液中基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)的表达情况及其与压疮愈合的关系。方法选择2017年7月至2018年4月在河北省人民医院就诊的Ⅳ期压疮患者39例,创面共59处,根据接诊时与治疗第4周末压疮愈合评估表(PUSH)评分差值进行分组,差值> 2分为愈合良好组(n=26),≤2分为愈合不良组(n=13)。按照统一方法评估、清洗及清创后,选择合适的治疗方案进行换药,追踪4周,采集接诊时、治疗第1周末、第2周末、第3周末、第4周末创面渗出液,酶联免疫吸附测定法检测2组创面渗出液中MMP-9、TIMP-1表达水平及MMP-9/TIMP-1比值的变化情况。数据比较采用t检验。结果接诊时及治疗第1周末2组MMP-9表达差异无统计学意义(t=1. 262、1. 944,P值均大于0. 05),而在治疗第2周末、第3周末、第4周末愈合不良组MMP-9表达水平分别为(189. 27±90. 15) ng/L、(176. 95±75. 47) ng/L、(149. 30±63. 08) ng/L,显著高于愈合良好组[(114. 97±70. 06) ng/L、(93. 75±55. 15) ng/L、(71. 62±41. 66) ng/L],差异有统计学意义(t=2. 835、3. 921、4. 608,P值均小于0. 05);不同时间点愈合良好组与愈合不良组TIMP-1表达水平比较,差异均无统计学意义(t=0. 346、0. 292、0. 047、0. 395、0. 999,P值均大于0. 05);接诊时及治疗第1周末2组MMP-9/TIMP-1比值差异均无统计学意义(t=1. 023、1. 134,P值均大于0. 05),而在治疗第2周末、第3周末、第4周末时愈合不良组MMP-9/TIMP-1比值分别为(38. 42±9. 25)、(33. 74±9. 58)、(29. 53±8. 04),显著高于愈合良好组的(30. 04±10. 67)、(25. 35±10. 18)、(21. 54±9. 29),差异均有统计学意义(t=2. 411、2. 473、2. 642,P值均小于0. 05)。结论创面渗出液中MMP-9表达水平及MMP-9/TIMP-1比值变化与压疮愈合有关,过高的MMP-9及MMP-9/TIMP-1不利于压疮的愈合。
Objective To investigate the relationship between the expression level of matrix metalloproteinase-9( MMP-9),matrix metalloproteinase inhibitor-1( TIMP-1) and the healing of pressure ulcer in the exudate of stage IV pressure ulcer. Methods A total of 39 patients( 59 wounds) with stage IV pressure ulcers from July 2017 to April 2018 in Hebei General Hospital were selected. The patients were divided into 2 groups according to the difference between receiving and the fourth weekend pressure ulcer scale for healing( PUSH) score. The difference > 2 points was a good healing group( n = 26) and ≤2 points was a poor healing group( n = 13). After evaluation,cleaning and debridement in accordance with the unified method,appropriate therapeutic regimen was selected to change dressings and track for four weeks. Collect the wound exudate at different time points: the time of diagnosis,the first weekend of treatment,the second weekend of treatment,the third weekend of treatment and the fourth weekend of treatment. The changes of MMP-9,TIMP-1 expression level and MMP-9/TIMP-1 ratio in wound effusion of the two groups were detected by enzyme-linked immuno sorbent assay. Date were compared by t test.Results There was no significant difference in MMP-9 expression between the two groups at the time of diagnosis and the first weekend of treatment( t = 1. 262,1. 944,with P values above 0. 05). At the second weekend,the third weekend,the fourth weekend of treatment,the expression level of MMP-9 in the poor healing group was( 189. 27 ± 90. 15) ng/L,( 176. 95 ± 75. 47) ng/L,( 149. 30 ± 63. 08) ng/L,which was significantly higher than that in the good healing group [( 114. 97 ± 70. 06) ng/L,( 93. 75 ± 55. 15) ng/L,( 71. 62 ± 41. 66) ng/L],the difference was statistically significant( t = 2. 835,3. 921,4. 608,with P values below 0. 05). There was no statistically significant difference in TIMP-1 expression between the good healing group and the poor healing group at different time points( t = 0. 346,0. 292,0. 047,0. 395,0. 999,with P values below 0. 05). There was no significant difference in the ratio of MMP-9/TIMP-1 between the two groups at the time of diagnosis and the first weekend of treatment( t = 1. 023,1. 134,with P values above0. 05). At the second,third and fourth weekends of treatment,MMP-9/TIMP-1 ratio in the poor healing group was( 38. 42 ± 9. 25),( 33. 74 ± 9. 58),( 29. 53 ± 8. 04),which was significantly higher than that in the good healing group [( 30. 04 ± 10. 67),( 25. 35 ± 10. 18),( 21. 54 ± 9. 29) ],the difference was statistically significant( t = 2. 411,2. 473,2. 642,with P values below 0. 05). Conclusion The changes of MMP-9 expression level and MMP-9/TIMP-1 ratio in wound exudate were related to the healing of pressure ulcer,while high level of expression of MMP-9 and MMP-9/TIMP-1 were not conducive to the healing of pressure ulcer.
Objective To investigate the relationship between the expression level of matrix metalloproteinase-9( MMP-9),matrix metalloproteinase inhibitor-1( TIMP-1) and the healing of pressure ulcer in the exudate of stage IV pressure ulcer. Methods A total of 39 patients( 59 wounds) with stage IV pressure ulcers from July 2017 to April 2018 in Hebei General Hospital were selected. The patients were divided into 2 groups according to the difference between receiving and the fourth weekend pressure ulcer scale for healing( PUSH) score. The difference > 2 points was a good healing group( n = 26) and ≤2 points was a poor healing group( n = 13). After evaluation,cleaning and debridement in accordance with the unified method,appropriate therapeutic regimen was selected to change dressings and track for four weeks. Collect the wound exudate at different time points: the time of diagnosis,the first weekend of treatment,the second weekend of treatment,the third weekend of treatment and the fourth weekend of treatment. The changes of MMP-9,TIMP-1 expression level and MMP-9/TIMP-1 ratio in wound effusion of the two groups were detected by enzyme-linked immuno sorbent assay. Date were compared by t test.Results There was no significant difference in MMP-9 expression between the two groups at the time of diagnosis and the first weekend of treatment( t = 1. 262,1. 944,with P values above 0. 05). At the second weekend,the third weekend,the fourth weekend of treatment,the expression level of MMP-9 in the poor healing group was( 189. 27 ± 90. 15) ng/L,( 176. 95 ± 75. 47) ng/L,( 149. 30 ± 63. 08) ng/L,which was significantly higher than that in the good healing group [( 114. 97 ± 70. 06) ng/L,( 93. 75 ± 55. 15) ng/L,( 71. 62 ± 41. 66) ng/L],the difference was statistically significant( t = 2. 835,3. 921,4. 608,with P values below 0. 05). There was no statistically significant difference in TIMP-1 expression between the good healing group and the poor healing group at different time points( t = 0. 346,0. 292,0. 047,0. 395,0. 999,with P values below 0. 05). There was no significant difference in the ratio of MMP-9/TIMP-1 between the two groups at the time of diagnosis and the first weekend of treatment( t = 1. 023,1. 134,with P values above0. 05). At the second,third and fourth weekends of treatment,MMP-9/TIMP-1 ratio in the poor healing group was( 38. 42 ± 9. 25),( 33. 74 ± 9. 58),( 29. 53 ± 8. 04),which was significantly higher than that in the good healing group [( 30. 04 ± 10. 67),( 25. 35 ± 10. 18),( 21. 54 ± 9. 29) ],the difference was statistically significant( t = 2. 411,2. 473,2. 642,with P values below 0. 05). Conclusion The changes of MMP-9 expression level and MMP-9/TIMP-1 ratio in wound exudate were related to the healing of pressure ulcer,while high level of expression of MMP-9 and MMP-9/TIMP-1 were not conducive to the healing of pressure ulcer.
引文
[1]贾晓明.压疮的流行病学特点及诊断与治疗进展[J/CD].中华损伤与修复杂志(电子版),2018,13(1):4-7.
[2]褚万立,郝岱峰.美国国家压疮咨询委员会2016年压力性损伤的定义和分期解读[J/CD].中华损伤与修复杂志(电子版),2018,13(1):64-68.
[3] Wei R,Chen HL,Zha ML,et al. Diabetes and pressure ulcer risk in hip fracture patients:a meta—analysis[J]. J Wound Care,2017,26(9):519-527.
[4] Muller M,Trocme C,Lardy B,et al. Matrix metalloproteinases and diabetic foot ulcers:the ratio of MMP-1 to TIMP-1 is a predictor of wound healing[J]. Diabet Med,2008,25(4):419-426.
[5] Bauer J,Phillips LG. MOC-PSSM CME article:Pressure Sores[J]. Plast Reconstr Surg,2008,121(1 Suppl):1-10.
[6]常学洪,常方媛,董建凤,等.基质金属蛋白酶及其组织抑制物在糖尿病足创面愈合中作用的研究概况[J].中国临床新医学,2017,10(9):916-919.
[7] Li DM,Zhang Y,Li Q,et a1. Low 25-Hydroxyvitamin D Level Is Associated with Peripheral Arterial Disease in Type 2 Diabetes Patients[J]. Arch Med Res,2016,47(1):49-54.
[8]吴俊,陈宁,孙海宁,等.影响老年压疮愈合的相关危险因素分析[J/CD].中华老年病研究电子杂志,2015,2(1):28-31.
[9]蒋琪霞,李晓华,胡素琴,等.压疮愈合计分对评价压疮清创效果的可行性及有效性分析[J].医学研究生学报,2010,23(5):518-521.
[10]邓红艳,郭春兰,周欣,等.两种银敷料对慢性伤口愈合及渗液酸碱度影响的比较[J].护理学杂志,2017,32(6):39-41.
[11] Tan Q,Wang W,Yang C,et al.α-ketoglutarate is associated with delayed wound healing in diabetes[J]. Clin Endocrinol(Oxf),2016,85(1):54-61.
[12]陈梦越,李乐之.慢性伤口细菌生物膜相关微环境的研究进展[J].中华护理杂志,2016,51(12):1483-1486.
[13] Bellayr I,Holden K,Mu X,et a1. Matrix metalloproteinase inhibition negatively affects muscle stem cell behavior[J]. Int J Clin Exp Pathol,2013,6(2):124-141.
[14] Lazaro JL,Izzo V,Meaume S,et al. Elevated levels of matrix metalloproteinases and chronic wound healing:an updated review of clinical evidence[J]. J Wound Care,2016,25(5):277-287.
[15] Tarlton JF,Bailey AJ,Crawford E,et al. Prognostic value of markers of collagen remodeling in venous ulcers[J]. Wound Repair Regen,1999,7(5):347-355.
[16] Bullen EC,Longaker MT,Updike DL,et al. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds[J]. J Invest Dermatol,1995,104(2):236-240.
[17] Lobmann R,Ambrosch A,Schultz G,et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients[J]. Diabetologia,2002,45(7):1011-1016.
[18]张静,李炳辉,李恭驰,等.基质金属蛋白酶-9及基质金属蛋白酶抑制剂-1在不同细菌负荷糖尿病创面组织的表达[J].中华实验外科杂志,2017,34(2):281-284.
[19]任国强,李炳辉,李恭驰,等.糖尿病创面基质金属蛋白酶9对血管内皮生长因子表达的影响[J/CD].中华损伤与修复杂志(电子版),2017,12(2):123-127.
[20] Ladwig GP,Robson MC,Liu R,et al. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers[J]. Wound Repair Regen,2002,10(1):26-37.
[21] Yager DR,Kulina RA,Gilman LA,et al. Wound fluids:a window into the wound environment[J]. Int J Low Extrem Wounds,2007,6(4):262-272.
[22] Spear M. Wound Exudate--The Good,the Bad,and the Ugly[J]. Plast Surg Nurs,2012,32(2):77-79.
[23] Siwik DA,Chang DI,Colucci WS. Interleukin-1 beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro[J]. Circ Res,2000,86(12):1259-1265.
[24] Trengove NJ,Stacey MC,Mac Auley S,et al. Analysis of the acute and chronic wound environments:the role of proteases and their inhibitors[J]. Wound Repair Regen,1999,7(6):442-452.
[25] Cooper DM,Yu EZ,Hennessey P,et al. Determination of endogenous cytokines in chronic wounds[J]. Ann Surg,1994,219(6):688-691; discussion 691-692.
[2]褚万立,郝岱峰.美国国家压疮咨询委员会2016年压力性损伤的定义和分期解读[J/CD].中华损伤与修复杂志(电子版),2018,13(1):64-68.
[3] Wei R,Chen HL,Zha ML,et al. Diabetes and pressure ulcer risk in hip fracture patients:a meta—analysis[J]. J Wound Care,2017,26(9):519-527.
[4] Muller M,Trocme C,Lardy B,et al. Matrix metalloproteinases and diabetic foot ulcers:the ratio of MMP-1 to TIMP-1 is a predictor of wound healing[J]. Diabet Med,2008,25(4):419-426.
[5] Bauer J,Phillips LG. MOC-PSSM CME article:Pressure Sores[J]. Plast Reconstr Surg,2008,121(1 Suppl):1-10.
[6]常学洪,常方媛,董建凤,等.基质金属蛋白酶及其组织抑制物在糖尿病足创面愈合中作用的研究概况[J].中国临床新医学,2017,10(9):916-919.
[7] Li DM,Zhang Y,Li Q,et a1. Low 25-Hydroxyvitamin D Level Is Associated with Peripheral Arterial Disease in Type 2 Diabetes Patients[J]. Arch Med Res,2016,47(1):49-54.
[8]吴俊,陈宁,孙海宁,等.影响老年压疮愈合的相关危险因素分析[J/CD].中华老年病研究电子杂志,2015,2(1):28-31.
[9]蒋琪霞,李晓华,胡素琴,等.压疮愈合计分对评价压疮清创效果的可行性及有效性分析[J].医学研究生学报,2010,23(5):518-521.
[10]邓红艳,郭春兰,周欣,等.两种银敷料对慢性伤口愈合及渗液酸碱度影响的比较[J].护理学杂志,2017,32(6):39-41.
[11] Tan Q,Wang W,Yang C,et al.α-ketoglutarate is associated with delayed wound healing in diabetes[J]. Clin Endocrinol(Oxf),2016,85(1):54-61.
[12]陈梦越,李乐之.慢性伤口细菌生物膜相关微环境的研究进展[J].中华护理杂志,2016,51(12):1483-1486.
[13] Bellayr I,Holden K,Mu X,et a1. Matrix metalloproteinase inhibition negatively affects muscle stem cell behavior[J]. Int J Clin Exp Pathol,2013,6(2):124-141.
[14] Lazaro JL,Izzo V,Meaume S,et al. Elevated levels of matrix metalloproteinases and chronic wound healing:an updated review of clinical evidence[J]. J Wound Care,2016,25(5):277-287.
[15] Tarlton JF,Bailey AJ,Crawford E,et al. Prognostic value of markers of collagen remodeling in venous ulcers[J]. Wound Repair Regen,1999,7(5):347-355.
[16] Bullen EC,Longaker MT,Updike DL,et al. Tissue inhibitor of metalloproteinases-1 is decreased and activated gelatinases are increased in chronic wounds[J]. J Invest Dermatol,1995,104(2):236-240.
[17] Lobmann R,Ambrosch A,Schultz G,et al. Expression of matrix-metalloproteinases and their inhibitors in the wounds of diabetic and non-diabetic patients[J]. Diabetologia,2002,45(7):1011-1016.
[18]张静,李炳辉,李恭驰,等.基质金属蛋白酶-9及基质金属蛋白酶抑制剂-1在不同细菌负荷糖尿病创面组织的表达[J].中华实验外科杂志,2017,34(2):281-284.
[19]任国强,李炳辉,李恭驰,等.糖尿病创面基质金属蛋白酶9对血管内皮生长因子表达的影响[J/CD].中华损伤与修复杂志(电子版),2017,12(2):123-127.
[20] Ladwig GP,Robson MC,Liu R,et al. Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers[J]. Wound Repair Regen,2002,10(1):26-37.
[21] Yager DR,Kulina RA,Gilman LA,et al. Wound fluids:a window into the wound environment[J]. Int J Low Extrem Wounds,2007,6(4):262-272.
[22] Spear M. Wound Exudate--The Good,the Bad,and the Ugly[J]. Plast Surg Nurs,2012,32(2):77-79.
[23] Siwik DA,Chang DI,Colucci WS. Interleukin-1 beta and tumor necrosis factor-alpha decrease collagen synthesis and increase matrix metalloproteinase activity in cardiac fibroblasts in vitro[J]. Circ Res,2000,86(12):1259-1265.
[24] Trengove NJ,Stacey MC,Mac Auley S,et al. Analysis of the acute and chronic wound environments:the role of proteases and their inhibitors[J]. Wound Repair Regen,1999,7(6):442-452.
[25] Cooper DM,Yu EZ,Hennessey P,et al. Determination of endogenous cytokines in chronic wounds[J]. Ann Surg,1994,219(6):688-691; discussion 691-692.