不同时间应用化疗药物对兔腹部皮肤切口愈合的影响及护理干预效果研究
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摘要
[目的]通过术前及术后不同时间应用化疗药物对切口愈合的影响,以及对切口部位组织VEGF表达及外周血TNF-α水平的观察,研究不同时间应用化疗药物对手术切口愈合的影响,探索最佳的手术联合化疗的时间；同时在此基础上,观察局部外用重组人粒细胞集落刺激因子、康复新液进行护理干预对皮肤切口愈合的影响,探讨其作用机理,为临床切口的愈合及护理提供理论依据。
[方法]1、将实验用大白兔48只,随机分为6组,空白对照组不进行化疗药物注射,另外5组分别于手术前3、0天和手术后2、4、6天于耳缘静脉注射表阿霉素,观察手术后1、3、5、7天切口VEGF和外周血TNF-α水平,术后7天观察各组切口愈合情况
2、选择对切口愈合影响最大的化疗时间进行护理干预研究,将大白兔40只,随机分为5组,空白组、对照组、重组人粒细胞集落刺激因子组、康复新高剂量组、康复新低剂量组。手术后7天分别取切口部位组织,分析两种干预对切口愈合的影响。
[结果]
1、手速前当日给予化疗组中化疗药物对切口愈合等级影响最大,切口愈合明显低于空白组(P<0.05);而术前3天,术后第2、4天应用化疗组虽愈合等级低于空白对照组,但无统计学意义。手术前当日应用化疗药物的感染程度明显高于空白组(P<0.05)。各组免疫组化染色,可见第1、3、5、7天VEGF免疫组化染色与空自组相比差别无意义。手术后第7天测TNF-α显示,手术前当日化p疗组9.8±4.31pg/mL.手术后2天化疗组11.1±3.8pg/mL.手术后4天化疗组11.3±3.18pg/mL,均低于空白组(P<0.05)。
2、对于手术前当天应用化疗药物,可见空白组、粒细胞集落刺激因子组及康复新液高剂量组术后第7天感染率均低于对照组(p<0.05)。免疫组化显示粒细胞集落刺激因子组和康复新液高剂量组明显高于空白组和对照组(P<0.05)。各组TNF-α水平无统计学差异(P>0.05)。
[结论]1.手术前当日给予化疗对切口愈合影响最大。2.手术前当天、手术后2、4天应用化疗药物会显著降低第7日外周血TNF-α水平,而各组切口部位VEGF表达无明显差异。3.粒细胞集落刺激因子及高浓度康复新液可以促进切口部位VEGF表达,从而促进切口愈合。
Objective To observe the influence of chemotherapy in different time on wound healing, the VEGF express in tissue at wound and TNF-a level in serum in order to define the optimal time of chemotherapy during operation. Furthermore, observe the effect of G-CSF and Kangfuxinye to wound healing, and explore mechanism for providing theoretical bases.
Methods Part1. New Zealand white rabbits (48cases), were randomly divided into6groups:normal group(8cases) was given surgery, other groups(8cases every group) were given infusion of epirubicin respectively on the day before the operation, three days before operation, two days after operation, four days after operation and six days after operation. At the same time to observe the VEGF express, TNF-a level and states of wound at the1st day,3rd day,5th day and7th day.
Part2. The rabbit(40cases) were randomly divided into5groups:normal group,control group, G-CSF group and Kangfuxinye high close treated group, Kangfuxinye low dose treat group. After7days of operation combing with chemotherapy, the grade of incision, the status of pathology, the level of VEGF and the level of TNF-a were observed.
Results Part1. There was worse effect of chemotherapy to wound healing on the day before the operation (p<0.05), the infected degree is higher than normal group. But there was no significant difference at three day before, two days after or three days after operation. For the VEGF levels, no difference was found in various groups. The TNF-α levels,9.8±4.31pg/mL on the day before the operation group,11.1±3.8pg/mL on two days after operation group,11.3±3.18pg/mL on four days after operation group, were lower than normal group (p<0.05)
Part2. The differences were observed including wound healing, VEGF and TNF-a in7th day after surgery. The VEGF in G-CSF group and Kangfuxinye high dose treated group were increased and the wound healing was better than the control group, but there was no difference of TNF-a in them.
Conclusion1. The chemotherapy on the day before the operation would cause the greatest worse effect of wound healing.2. No difference of VEGF level were found in various time of operation with chemotherapy, but the TNF-α levels on the day before the operation group, two days after operation, four days after operation group were lower than normal group.3. The G-CSF and Kangfuxinye can increase the VEGF expression of incision sites, and it is helpful to wound healing after treatment with both chemotherapy and surgery.
[方法]1、将实验用大白兔48只,随机分为6组,空白对照组不进行化疗药物注射,另外5组分别于手术前3、0天和手术后2、4、6天于耳缘静脉注射表阿霉素,观察手术后1、3、5、7天切口VEGF和外周血TNF-α水平,术后7天观察各组切口愈合情况
2、选择对切口愈合影响最大的化疗时间进行护理干预研究,将大白兔40只,随机分为5组,空白组、对照组、重组人粒细胞集落刺激因子组、康复新高剂量组、康复新低剂量组。手术后7天分别取切口部位组织,分析两种干预对切口愈合的影响。
[结果]
1、手速前当日给予化疗组中化疗药物对切口愈合等级影响最大,切口愈合明显低于空白组(P<0.05);而术前3天,术后第2、4天应用化疗组虽愈合等级低于空白对照组,但无统计学意义。手术前当日应用化疗药物的感染程度明显高于空白组(P<0.05)。各组免疫组化染色,可见第1、3、5、7天VEGF免疫组化染色与空自组相比差别无意义。手术后第7天测TNF-α显示,手术前当日化p疗组9.8±4.31pg/mL.手术后2天化疗组11.1±3.8pg/mL.手术后4天化疗组11.3±3.18pg/mL,均低于空白组(P<0.05)。
2、对于手术前当天应用化疗药物,可见空白组、粒细胞集落刺激因子组及康复新液高剂量组术后第7天感染率均低于对照组(p<0.05)。免疫组化显示粒细胞集落刺激因子组和康复新液高剂量组明显高于空白组和对照组(P<0.05)。各组TNF-α水平无统计学差异(P>0.05)。
[结论]1.手术前当日给予化疗对切口愈合影响最大。2.手术前当天、手术后2、4天应用化疗药物会显著降低第7日外周血TNF-α水平,而各组切口部位VEGF表达无明显差异。3.粒细胞集落刺激因子及高浓度康复新液可以促进切口部位VEGF表达,从而促进切口愈合。
Objective To observe the influence of chemotherapy in different time on wound healing, the VEGF express in tissue at wound and TNF-a level in serum in order to define the optimal time of chemotherapy during operation. Furthermore, observe the effect of G-CSF and Kangfuxinye to wound healing, and explore mechanism for providing theoretical bases.
Methods Part1. New Zealand white rabbits (48cases), were randomly divided into6groups:normal group(8cases) was given surgery, other groups(8cases every group) were given infusion of epirubicin respectively on the day before the operation, three days before operation, two days after operation, four days after operation and six days after operation. At the same time to observe the VEGF express, TNF-a level and states of wound at the1st day,3rd day,5th day and7th day.
Part2. The rabbit(40cases) were randomly divided into5groups:normal group,control group, G-CSF group and Kangfuxinye high close treated group, Kangfuxinye low dose treat group. After7days of operation combing with chemotherapy, the grade of incision, the status of pathology, the level of VEGF and the level of TNF-a were observed.
Results Part1. There was worse effect of chemotherapy to wound healing on the day before the operation (p<0.05), the infected degree is higher than normal group. But there was no significant difference at three day before, two days after or three days after operation. For the VEGF levels, no difference was found in various groups. The TNF-α levels,9.8±4.31pg/mL on the day before the operation group,11.1±3.8pg/mL on two days after operation group,11.3±3.18pg/mL on four days after operation group, were lower than normal group (p<0.05)
Part2. The differences were observed including wound healing, VEGF and TNF-a in7th day after surgery. The VEGF in G-CSF group and Kangfuxinye high dose treated group were increased and the wound healing was better than the control group, but there was no difference of TNF-a in them.
Conclusion1. The chemotherapy on the day before the operation would cause the greatest worse effect of wound healing.2. No difference of VEGF level were found in various time of operation with chemotherapy, but the TNF-α levels on the day before the operation group, two days after operation, four days after operation group were lower than normal group.3. The G-CSF and Kangfuxinye can increase the VEGF expression of incision sites, and it is helpful to wound healing after treatment with both chemotherapy and surgery.
引文
[1]Goldie JH. Scientific basis for adjuvant and primary (neoadjuvant) chemotherapy [J]. Semin Oneol,1987,14(1):1-7. sif
[2]Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases:VEGFs, angiopoietins, and ephrins in vascular development[J]. Genes Dev,1999,13(9):1055-1066.
[3]潘秀花,杨占山,杨晶,等.VEGF和Ang-1在皮肤创伤和放射性烧伤愈合过程中的表达[J].中华放射医学与防护杂志,2007,27(3)：219-222.
[4]夏鹏,童文祥,喻永敏,等.大鼠皮肤切创愈合过程中VEGF,TGF-β1蛋白的表达[J].重庆医科大学学报,2010,35(8)：1167-1171.
[5]澎湃,郭树忠,韩岩,等.VEGF对创伤组织中KDR, bFGF和PDGF mRNA表达的影响[J].中国美容医学,2004,13(3)：266-268.
[6]Clark RA. Regulation of fibroplasias in cutaneous wound repair[J]. Am J Med Sci,1993,360(1):42-48.
[7]赵忠信.重组人粒细胞/巨噬细胞集落刺激因子的临床新用途[J].中国肿瘤生物治疗杂志,2000,7(1):71.
[8]戴艳丽,王宏丽,商亚娟,等.重组人粒细胞集落刺激因子促进药物性溃疡愈合的实验研究[J].解放军护理杂志,2005,22(1):16-17.
[9]李珊瑚,李勇敏.康复新对家兔创伤愈合的影响[J].临床和实验医学杂志,2006,5(6)：731.
[10]肖旋,李晓升.康复新液治疗急性牙周炎的临床运用观察[J].中国误诊学杂志,2008,8(4)：807.
[11]凌瑞,张洪伟,李纪鹏.结直肠癌术后早期应用奥沙利铂联合5-FU辅助化疗的安全性[J].第四军医大学学报,2003,24(20)：1890-1892.
[12]Garlet GP, Horwat R, Ray HL Jr, et al. Expression analysis of wound healing genes in human periapical granulomas of progressive and stable nature[J]. Journal of endodontics,2012,38:185-190.
[13]Khalil N, Bereznay 0, Sporn. M. et al. Macrophage production of transforming growth factor β and fibroblast collagen synthesis in chronic pulmonary inflammation[J]. J Exp Med,1989,170(3):727.
[14]彭开勤.切口愈合的影响因素[J].临床外科杂志,2007,15(9)：588-589.
[15]蓝英,蓝丽智.清创缝合术后缩短伤口愈合时间的探讨[J].广西医学,2009,31(3)：399-400.
[16]杨丽彩,李萍,徐宝婴,等.中药珠香散对慢性皮肤伤口愈合过程中TGF β 1mRNA表达的影响[J].中国病理生理杂志,2001,17(5)：471-472.
[17]任淑勋,陈鸿骏,董世炎,等.手术联合阿霉素化疗导致切口裂开1例[J].中国肿瘤临床,1991,S1：288.
[18]Senger DR, et al. A highly conserved vascular permeability factor by a variety of human and rodent tumor cell lines[J]. Cancer Research, 1986:46(11):5629-5632.
[19]John Christoforidis, Robert Ricketts, Cedric Pratt, et al. The effect of intravitreal anti-VEGF agents on peripheral wound healing in a rabbit model [J]. Clinical Ophthalmology,2012,6:61-69.
[20]Matias MA, Saunus JM, Ivanovski S, et al. Accelerated wound healing phenotype in Interleukin 12/23 deficient mice[J]. Journal of Inflammation,2011,20:39-49.
[21]彭瑞云,王德文,高亚兵,等.大鼠皮肤伤口内VEGF基因表达的定量病理研究[J].中国体视学与图像分析,2001,6(2)：95-98.
[22]宣兆艳,卢英强,刘东辉,等.IL,-1及VEGF在大鼠皮肤切创愈合过程中的免疫组织化学表达[J].吉林大学学报(医学版),2007,33(3)：460-463.
[23]Makoto Nogami, Tomoaki Hoshi, Mayumi Kinoshita, et al. Vascular endothelial growth factor expression in rat skin incision wound[J]. Medical Molecular Morphology,2007,40(2):82-87.
[24]赵雷,王莉,姜叙诚,等.hVEGF基因工程生物膜对全层皮肤缺损创而愈合的影响[J].上海交通大学学报,2006,26(9)：1015-1018.
[25]吴洋,周树夏,李秀娟,等.外源性rh-tnf-α局部介入对创伤愈合的影响[J].第二军医大学学报,2001,22(12)：1120-1122.
[26]Werner S, Grose R. Regulation of wound healing by growth factors and cytokines[J]. Physiol Rev,2003,83 (3):835-870.
[27]Goldberg MT, Han YP, Yan C, et al. TNF-a suppresses-smooth muscle actin expression in human dermal fibroblasts:an implication for abnormal wound healing[J].J Invest Dermatol,2007,127 (11):2645-2655.
[28]余红梅,胡宏鸯,吴霞,等.EGCG改善高浓度TNF-α对人皮肤创伤愈合中成纤维细胞的抑制作用[J].中国病理生理杂志,2012,28(1)：155-158.
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[2]Gale NW, Yancopoulos GD. Growth factors acting via endothelial cell-specific receptor tyrosine kinases:VEGFs, angiopoietins, and ephrins in vascular development[J]. Genes Dev,1999,13(9):1055-1066.
[3]潘秀花,杨占山,杨晶,等.VEGF和Ang-1在皮肤创伤和放射性烧伤愈合过程中的表达[J].中华放射医学与防护杂志,2007,27(3)：219-222.
[4]夏鹏,童文祥,喻永敏,等.大鼠皮肤切创愈合过程中VEGF,TGF-β1蛋白的表达[J].重庆医科大学学报,2010,35(8)：1167-1171.
[5]澎湃,郭树忠,韩岩,等.VEGF对创伤组织中KDR, bFGF和PDGF mRNA表达的影响[J].中国美容医学,2004,13(3)：266-268.
[6]Clark RA. Regulation of fibroplasias in cutaneous wound repair[J]. Am J Med Sci,1993,360(1):42-48.
[7]赵忠信.重组人粒细胞/巨噬细胞集落刺激因子的临床新用途[J].中国肿瘤生物治疗杂志,2000,7(1):71.
[8]戴艳丽,王宏丽,商亚娟,等.重组人粒细胞集落刺激因子促进药物性溃疡愈合的实验研究[J].解放军护理杂志,2005,22(1):16-17.
[9]李珊瑚,李勇敏.康复新对家兔创伤愈合的影响[J].临床和实验医学杂志,2006,5(6)：731.
[10]肖旋,李晓升.康复新液治疗急性牙周炎的临床运用观察[J].中国误诊学杂志,2008,8(4)：807.
[11]凌瑞,张洪伟,李纪鹏.结直肠癌术后早期应用奥沙利铂联合5-FU辅助化疗的安全性[J].第四军医大学学报,2003,24(20)：1890-1892.
[12]Garlet GP, Horwat R, Ray HL Jr, et al. Expression analysis of wound healing genes in human periapical granulomas of progressive and stable nature[J]. Journal of endodontics,2012,38:185-190.
[13]Khalil N, Bereznay 0, Sporn. M. et al. Macrophage production of transforming growth factor β and fibroblast collagen synthesis in chronic pulmonary inflammation[J]. J Exp Med,1989,170(3):727.
[14]彭开勤.切口愈合的影响因素[J].临床外科杂志,2007,15(9)：588-589.
[15]蓝英,蓝丽智.清创缝合术后缩短伤口愈合时间的探讨[J].广西医学,2009,31(3)：399-400.
[16]杨丽彩,李萍,徐宝婴,等.中药珠香散对慢性皮肤伤口愈合过程中TGF β 1mRNA表达的影响[J].中国病理生理杂志,2001,17(5)：471-472.
[17]任淑勋,陈鸿骏,董世炎,等.手术联合阿霉素化疗导致切口裂开1例[J].中国肿瘤临床,1991,S1：288.
[18]Senger DR, et al. A highly conserved vascular permeability factor by a variety of human and rodent tumor cell lines[J]. Cancer Research, 1986:46(11):5629-5632.
[19]John Christoforidis, Robert Ricketts, Cedric Pratt, et al. The effect of intravitreal anti-VEGF agents on peripheral wound healing in a rabbit model [J]. Clinical Ophthalmology,2012,6:61-69.
[20]Matias MA, Saunus JM, Ivanovski S, et al. Accelerated wound healing phenotype in Interleukin 12/23 deficient mice[J]. Journal of Inflammation,2011,20:39-49.
[21]彭瑞云,王德文,高亚兵,等.大鼠皮肤伤口内VEGF基因表达的定量病理研究[J].中国体视学与图像分析,2001,6(2)：95-98.
[22]宣兆艳,卢英强,刘东辉,等.IL,-1及VEGF在大鼠皮肤切创愈合过程中的免疫组织化学表达[J].吉林大学学报(医学版),2007,33(3)：460-463.
[23]Makoto Nogami, Tomoaki Hoshi, Mayumi Kinoshita, et al. Vascular endothelial growth factor expression in rat skin incision wound[J]. Medical Molecular Morphology,2007,40(2):82-87.
[24]赵雷,王莉,姜叙诚,等.hVEGF基因工程生物膜对全层皮肤缺损创而愈合的影响[J].上海交通大学学报,2006,26(9)：1015-1018.
[25]吴洋,周树夏,李秀娟,等.外源性rh-tnf-α局部介入对创伤愈合的影响[J].第二军医大学学报,2001,22(12)：1120-1122.
[26]Werner S, Grose R. Regulation of wound healing by growth factors and cytokines[J]. Physiol Rev,2003,83 (3):835-870.
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