巨噬细胞及GM-CSF对大鼠DIEP皮瓣成活影响的实验研究
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摘要
腹壁下动脉穿支(DIEP)皮瓣作为穿支皮瓣的代表,在最近的十几年中得到了广泛的临床应用。目前,DIEP皮瓣已经超过TRAM皮瓣成为自体组织乳房再造的首选术式。DIEP皮瓣再造乳房的优点是拥有充足的组织量,腹壁皮肤的色泽、质地与受区十分相似,再造的乳房外观、颜色与手感均较满意;皮瓣血管蒂较长,十分有利于皮瓣塑形,且腹壁下动脉的口径与胸廓内动脉及胸背动脉的口径相当,利于血管吻合;DIEP皮瓣乳房再造的最大优势体现在供区的并发症发生率下降,该技术保留了腹直肌前鞘及大部分腹直肌,减少了术后腹壁疼痛、薄弱、腹壁膨出和腹壁疝的发生率,最大程度地保护了供区,使患者获得外形美观效果的同时保留了供区的功能,此外手术恢复时间亦缩短。但DIEP皮瓣乳房再造仍然存在并发症,人们享有其优势的代价是不仅增加了手术的复杂性,而且因为人为减少了腹直肌肌皮穿支的数量,从而减少了皮瓣的血供,理论上增加了皮瓣部分坏死和脂肪液化的几率。如何提高乳房再造中DIEP皮瓣的成活率,是整形外科和肿瘤外科面临的一道难题。
当前促进皮瓣成活的研究聚集在以血管内皮生长因子(VEGF)为代表的各种细胞因子的研究上。目前普遍认为VEGF是一种最重要的血管生成因子,在治疗性血管生成中具有重要意义。但是,以VEGF为代表的多种生长因子在病理性血管生成中同样发挥着重要作用。肿瘤学研究表明VEGF是目前所知作用最强、选择性最高的内皮细胞丝裂原,是肿瘤血管生成中的重要调节因子,在许多实体肿瘤的生长、转移中起着极为重要的作用。我们认为,通过基因治疗的方法将具有潜在的促进肿瘤生长与转移的VGEF用于乳癌术后乳房再造的患者以促进再造乳房皮瓣成活是不合适的。
重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)已应用于临床多年,是乳腺癌病人辅助化疗时的常规用药。在乳腺癌治疗的临床工作中我们发现,因化疗造成的白细胞低于正常的患者在接受rhGM-CSF治疗后术区原本愈合不良的创面会很快愈合,所以我们设想是否单核/巨噬细胞抑或GM-CSF存在促进皮瓣血管生成的作用?文献显示:近几年研究GM-CSF促进创面愈合的报道比较多,而且绝大部分获得了积极的结果。但将GM-CSF直接应用于皮瓣,观察其对皮瓣成活影响的研究很少。因此我们将GM-CSF及过继巨噬细胞用于乳房再造常规应用的DIEP皮瓣模型中,研究其对皮瓣成活的影响,具有特殊的临床意义。
本实验的第一部分研究了大鼠腹部皮瓣的结构特点,并改进了rat-DIEP皮瓣的制作过程,不解剖腹直肌,仅在腹直肌前鞘层面选择穿支血管并切断其它血供,形成DIEP皮瓣,在手术时间缩短的同时,使模型具有更好的稳定性和可重复性。第一部分实验中我们成功建立了稳定的rat-DIEP模型,并形成了相对简单、容易推广的操作流程。使rat-DIEP可以作为常规模型进行皮瓣成活的实验研究。模型形成后,我们通过大体观察及HE染色后的组织学检查记录了皮瓣成活的进程。通过免疫组化以VWF作为血管内皮的识别标志,检测皮瓣各个时点的微血管密度(MVD)的变化,应用苦味酸天狼猩红染色及偏振光显微图像定量分析技术检测皮瓣内胶原含量,并描绘出在无干预情况下rat-DIEP皮瓣形成过程中MVD及胶原含量与各时点之间的变化关系。
第二部分实验的目的是研究GM-CSF以及巨噬细胞(Mφ))对大鼠皮瓣成活的影响。我们应用大鼠腹腔直接灌洗的方法,经过分离、纯化获得大鼠Mφ。实验中将模型动物分为四组,分别于皮瓣皮下应用重组大鼠GM-CSF,GM-CSF联合过继大鼠Mφ,过继大鼠Mφ及生理盐水。术后第7天取皮瓣标本,进行皮瓣成活面积的测定,以及免疫组化MVD检测,Masson染色检测皮瓣组织内胶原含量。活化的Mφ可分泌100多种物质,其中包括大量细胞因子,可直接诱导新生血管生长。从理论上来说,Mφ应该具有促进皮瓣成活的治疗作用,但是,我们的实验结果显示过继的Mφ没有增加大鼠皮瓣的成活比率。在皮瓣内MVD检测中,单纯应用Mφ干预皮瓣成活的T组皮瓣MVD高于对照组,但无统计学意义。在皮瓣胶原含量检测中我们发现,单纯应用Mφ干预组胶原含量明显低于对照组(p＜0.05),这可能因为Mφ过量激活金属蛋白酶导致胶原分解过程延长的结果。与其相反,应用GM-CSF组及其联合应用Mφ组皮瓣成活率高于对照组(p＜0.05),其皮瓣MVD和胶原含量均明显高于对照组(p＜0.001)。
第二部分实验得到的结论是:重组大鼠GM-CSF及其联合过继的大鼠Mφ皮下注射能够提高大鼠DIEP皮瓣的成活率;并且能够明显提高术后第7天大鼠DIEP皮瓣的MVD及胶原含量。过继大鼠Mφ单独应用不能明显提高大鼠DIEP皮瓣的成活率。
第三部分实验的目的是探讨重组大鼠GM-CSF及其与过继大鼠Mφ联合应用促进大鼠DIEP皮瓣成活的分子机制。本实验中,我们利用RT-PCR技术检测第二部分实验中各组动物皮瓣内的多项基因表达,包括EMMPRIN、MMP2、TIMP1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1、VEGF、EGFR及VEGFR等。比较它们在各组皮瓣中的表达情况,从基因水平探讨GM-CSF及其联合Mφ促进皮瓣成活的机理。实验结果显示,应用GM-CSF组皮瓣EMMPRIN、MMP2、CollagenⅠ、EGF和EGFR基因表达高于对照组;联合应用GM-CSF+Mφ组皮瓣EMMPRIN、MMP2、TIMP 1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1和EGFR基因表达高于对照组;应用Mφ组皮瓣EMMPRIN、MMP2、TGF-β1和EGF基因表达高于对照组。这些基因的上调从分子水平解释了实验组大鼠皮瓣成活率提高的原因。
综上所述,本实验研究的结论认为大鼠DIEP模型是一个稳定可靠的皮瓣研究模型;重组大鼠GM-CSF及其联合应用过继Mφ可以提高大鼠DIEP皮瓣的成活率;我们通过更进一步的研究认为,重组大鼠GM-CSF及其联合应用过继Mφ上调了皮瓣内部分基因表达的水平,有利于皮瓣血管生成和胶原重塑,最终促进了皮瓣的成活。
DIEP flap has been widely used in clinical as a representation of perforator flaps in recent decades.With the merit of no rectus abdominis muscle sacrifice,DIEP flap has become the first choice of therapy for autogenous tissue breast reconstruction over TRAM flap.The other merits of DIEP flap for breast reconstruction are ample tissue quantity,similar skin color and texture to the recipient area,satisfaction about the appearance,color and handle of the reconstructed breast.It is easy for the flap plasticity by long flap vessel pedicle.The caliber of the inferior epigastric artery is similar to the thoracodorsal artery and internal thoracic artery which makes it easy for vessel anastomose.The biggest advantage of DIEP breast reconstruction is the decrease of donor site complications.This technique preserves the rectus abdominis anterior sheath,reduces the incidence of postoperational abdomen wall pain, weakness,abdomen wall bulge and hernia and protect the donor site farthest.It can gain function recovery and cosmetic results and reduce the recovery time.Yet there are still complications with DIEP breast reconstruction.Choosing DIEP will increase the complexity of the operation and decrease the blood supply of the flap by cutting down the quantity of the rectus abdominis muscle perforator.It will increase the rate of flap partial necrosis and fat liquefaction in theory.It is still a puzzle in plastic surgery and oncologic surgery how to increase the survival rate of DIEP flap in breast reconstruction.
Now the focus on the research about promoting flap survival is the study around VEGF and other growth factor such as bFGF、PDGF、TGF-β.It has been considered that VEGF is the most important vessel growth factor and significant in therapeutic vessel formation.But VEGF also plays important role in pathological vessel formation.The study of oncology indicates that VEGF is known as endothelium mitogen with most effectivity and high selectivity at present and the important regulatory factor in tomor vessel formation.It is important in growth and metastasis of many solid tumor.We think it is not appropriate to promote the flap survival of patients received breast reconstruction with breast cancer by gene therapy which conducts VEGF with potential ability of tumor growth and metastasis promotion. Recombined human Granulocyte-macrophage colony-stimulating factor has been used in clinic for years,it is routine therapy for breast cancer assistant chemotherapy. In clinical works,we found that the wound of poor healing in the patients whose leucocyte is lower than normal caused by chemotherapy would heal quickly after receiving rhGM-CSF therapy.So we assume whether monocyte or macrophage or GM-CSF can promote vessel formation of flap.Literatures indicate that more and more research is about GM-CSF promoting wound healing recently and most of them show positive results.But there are few research about applying GM-CSF directly on flap and observing its effect on flap survival.So we design DIEP model with GM-CSF macrophage and research its influence on flap survival.It has special significance in clinic.
In th first part of these experiment,we investigate the structure character of rat abdominal flap and improve the havesting process of rat-DIEP flap.We choose the perforator on the layer of rectus abdominis anterior sheath and cut down other blood supply without anatomy of rectus abdominis muscle,and it can shorten the operation time and process more operation in one day.And this will help us degrade the operation,makes the model stable and reproducible.In the first part of the experiment we succeed building a stable rat-DIEP model and form a relatively easy and easy handled process.So rat-DIEP can be a routine model for flap survival research. After model formation,we can record the flap survival progress through general observation and histological examination with HE staining and measure the MVD variety of different time point through immunohistochemistry identified by VWF.We also can analyse the collagen quantity of flap with method of picric-sirius red polarized light.We can trace out the relationship between MVD and collagen quantity in different time during the rat-DIEP flap formation without intervention.
The objective of the second part of experiment is to study the influence of GM-CSF and Mψto the survival rate of rat flap.We directly lavaged the rat's abdomen and gained macrophage after separation and purification.The model rats were divided into 4 groups,which were subcutaneous injection recombined rat GM-CSF group,GM-CSF combining adoptive rat Mψgroup,adoptive rat Mψgroup and saline group.The samples were collected the 7th day after operation,the flap survival area were measured,immunohistochemistry MVD were detected and collagen quantity were examined by Masson staining.Activated Mψcan excrete more than 100 kinds of substance including massive cellular factor which can induce vessel growth directly.In theory,Mψshould promote flap survival,yet in our experiment it shows no increase of flap survival ratio in adoptive rat Mψgroup.In the examination of flap MVD,it has no statistical significance between MψT group and control group. In the collagen quantity examination,we found it was lower in the Mψgroup than the control group(p＜0.05).The reason may be Mψover activate metalloproteinase to lead to prolong the collagen decomposition.On the contrary,the flap survival rate is higher in GM-CSF combining adoptive rat Mψgroup than the control group(p＜0.05) and its MVD and collagen quantity is higher than the control group(p＜0.001).
The conclusion from the second part of the experiment is subcutaneous injection recombined rat GM-CSF and GM-CSF combining adoptive rat Mψcan elevate the survival rate of rat DIEP flap.adoptive rat Mψcannot elevate the survival rate of rat DIEP flap.Recombined rat GM-CSF and GM-CSF combining adoptive rat Mψcan distinctively elevate the MVD and collagen quantity of rat DIEP flap the 7th day after operation.
The objective of the third part of the experiment is to explore the molecular mechanism of recombined rat GM-CSF and GM-CSF combining adoptive rat Mψpromoting rat DIEP flap survival.In the experiment,we test multiple gene expression in the flap we used in the second part with the technique of RT-PCR,including EMMPRIN、MMP2、TIMP1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1、VEGF、EGFR and VEGFR et al.We compared their expression in the flap and discuss the mechanism of promoting flap survival by GM-CSF and GM-CSF combining adoptive rat Mψin gene level.The result showed EMMPRIN、MMP2、CollagenⅠ、EGF和EGFR expression was higher in GM-CSF group than the control group.EMMPRIN、MMP2、TIMP1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1 and EGFR expression in combining GM-CSF+Mψgroup was higher than the control group.EMMPRIN、MMP2、TGF-β1 and EGF expression was high in Mψgroup than the control group. The upregulation the expression of these gene on the molecular level can explain why the flap survival rate was higher in the experiment group.
In conclusion,we find rat DIEP model is a stable and reliable flap study model and recombined rat GM-CSF and GM-CSF combining adoptive rat Mψcan elevate the survival rate of rat DIEP flap.In further research,we find it can upregulate the some gene expression of the flap to promote vessel formation and collagen modeling, it lead to promote flap survival eventually.
当前促进皮瓣成活的研究聚集在以血管内皮生长因子(VEGF)为代表的各种细胞因子的研究上。目前普遍认为VEGF是一种最重要的血管生成因子,在治疗性血管生成中具有重要意义。但是,以VEGF为代表的多种生长因子在病理性血管生成中同样发挥着重要作用。肿瘤学研究表明VEGF是目前所知作用最强、选择性最高的内皮细胞丝裂原,是肿瘤血管生成中的重要调节因子,在许多实体肿瘤的生长、转移中起着极为重要的作用。我们认为,通过基因治疗的方法将具有潜在的促进肿瘤生长与转移的VGEF用于乳癌术后乳房再造的患者以促进再造乳房皮瓣成活是不合适的。
重组人粒细胞巨噬细胞集落刺激因子(rhGM-CSF)已应用于临床多年,是乳腺癌病人辅助化疗时的常规用药。在乳腺癌治疗的临床工作中我们发现,因化疗造成的白细胞低于正常的患者在接受rhGM-CSF治疗后术区原本愈合不良的创面会很快愈合,所以我们设想是否单核/巨噬细胞抑或GM-CSF存在促进皮瓣血管生成的作用?文献显示:近几年研究GM-CSF促进创面愈合的报道比较多,而且绝大部分获得了积极的结果。但将GM-CSF直接应用于皮瓣,观察其对皮瓣成活影响的研究很少。因此我们将GM-CSF及过继巨噬细胞用于乳房再造常规应用的DIEP皮瓣模型中,研究其对皮瓣成活的影响,具有特殊的临床意义。
本实验的第一部分研究了大鼠腹部皮瓣的结构特点,并改进了rat-DIEP皮瓣的制作过程,不解剖腹直肌,仅在腹直肌前鞘层面选择穿支血管并切断其它血供,形成DIEP皮瓣,在手术时间缩短的同时,使模型具有更好的稳定性和可重复性。第一部分实验中我们成功建立了稳定的rat-DIEP模型,并形成了相对简单、容易推广的操作流程。使rat-DIEP可以作为常规模型进行皮瓣成活的实验研究。模型形成后,我们通过大体观察及HE染色后的组织学检查记录了皮瓣成活的进程。通过免疫组化以VWF作为血管内皮的识别标志,检测皮瓣各个时点的微血管密度(MVD)的变化,应用苦味酸天狼猩红染色及偏振光显微图像定量分析技术检测皮瓣内胶原含量,并描绘出在无干预情况下rat-DIEP皮瓣形成过程中MVD及胶原含量与各时点之间的变化关系。
第二部分实验的目的是研究GM-CSF以及巨噬细胞(Mφ))对大鼠皮瓣成活的影响。我们应用大鼠腹腔直接灌洗的方法,经过分离、纯化获得大鼠Mφ。实验中将模型动物分为四组,分别于皮瓣皮下应用重组大鼠GM-CSF,GM-CSF联合过继大鼠Mφ,过继大鼠Mφ及生理盐水。术后第7天取皮瓣标本,进行皮瓣成活面积的测定,以及免疫组化MVD检测,Masson染色检测皮瓣组织内胶原含量。活化的Mφ可分泌100多种物质,其中包括大量细胞因子,可直接诱导新生血管生长。从理论上来说,Mφ应该具有促进皮瓣成活的治疗作用,但是,我们的实验结果显示过继的Mφ没有增加大鼠皮瓣的成活比率。在皮瓣内MVD检测中,单纯应用Mφ干预皮瓣成活的T组皮瓣MVD高于对照组,但无统计学意义。在皮瓣胶原含量检测中我们发现,单纯应用Mφ干预组胶原含量明显低于对照组(p＜0.05),这可能因为Mφ过量激活金属蛋白酶导致胶原分解过程延长的结果。与其相反,应用GM-CSF组及其联合应用Mφ组皮瓣成活率高于对照组(p＜0.05),其皮瓣MVD和胶原含量均明显高于对照组(p＜0.001)。
第二部分实验得到的结论是:重组大鼠GM-CSF及其联合过继的大鼠Mφ皮下注射能够提高大鼠DIEP皮瓣的成活率;并且能够明显提高术后第7天大鼠DIEP皮瓣的MVD及胶原含量。过继大鼠Mφ单独应用不能明显提高大鼠DIEP皮瓣的成活率。
第三部分实验的目的是探讨重组大鼠GM-CSF及其与过继大鼠Mφ联合应用促进大鼠DIEP皮瓣成活的分子机制。本实验中,我们利用RT-PCR技术检测第二部分实验中各组动物皮瓣内的多项基因表达,包括EMMPRIN、MMP2、TIMP1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1、VEGF、EGFR及VEGFR等。比较它们在各组皮瓣中的表达情况,从基因水平探讨GM-CSF及其联合Mφ促进皮瓣成活的机理。实验结果显示,应用GM-CSF组皮瓣EMMPRIN、MMP2、CollagenⅠ、EGF和EGFR基因表达高于对照组;联合应用GM-CSF+Mφ组皮瓣EMMPRIN、MMP2、TIMP 1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1和EGFR基因表达高于对照组;应用Mφ组皮瓣EMMPRIN、MMP2、TGF-β1和EGF基因表达高于对照组。这些基因的上调从分子水平解释了实验组大鼠皮瓣成活率提高的原因。
综上所述,本实验研究的结论认为大鼠DIEP模型是一个稳定可靠的皮瓣研究模型;重组大鼠GM-CSF及其联合应用过继Mφ可以提高大鼠DIEP皮瓣的成活率;我们通过更进一步的研究认为,重组大鼠GM-CSF及其联合应用过继Mφ上调了皮瓣内部分基因表达的水平,有利于皮瓣血管生成和胶原重塑,最终促进了皮瓣的成活。
DIEP flap has been widely used in clinical as a representation of perforator flaps in recent decades.With the merit of no rectus abdominis muscle sacrifice,DIEP flap has become the first choice of therapy for autogenous tissue breast reconstruction over TRAM flap.The other merits of DIEP flap for breast reconstruction are ample tissue quantity,similar skin color and texture to the recipient area,satisfaction about the appearance,color and handle of the reconstructed breast.It is easy for the flap plasticity by long flap vessel pedicle.The caliber of the inferior epigastric artery is similar to the thoracodorsal artery and internal thoracic artery which makes it easy for vessel anastomose.The biggest advantage of DIEP breast reconstruction is the decrease of donor site complications.This technique preserves the rectus abdominis anterior sheath,reduces the incidence of postoperational abdomen wall pain, weakness,abdomen wall bulge and hernia and protect the donor site farthest.It can gain function recovery and cosmetic results and reduce the recovery time.Yet there are still complications with DIEP breast reconstruction.Choosing DIEP will increase the complexity of the operation and decrease the blood supply of the flap by cutting down the quantity of the rectus abdominis muscle perforator.It will increase the rate of flap partial necrosis and fat liquefaction in theory.It is still a puzzle in plastic surgery and oncologic surgery how to increase the survival rate of DIEP flap in breast reconstruction.
Now the focus on the research about promoting flap survival is the study around VEGF and other growth factor such as bFGF、PDGF、TGF-β.It has been considered that VEGF is the most important vessel growth factor and significant in therapeutic vessel formation.But VEGF also plays important role in pathological vessel formation.The study of oncology indicates that VEGF is known as endothelium mitogen with most effectivity and high selectivity at present and the important regulatory factor in tomor vessel formation.It is important in growth and metastasis of many solid tumor.We think it is not appropriate to promote the flap survival of patients received breast reconstruction with breast cancer by gene therapy which conducts VEGF with potential ability of tumor growth and metastasis promotion. Recombined human Granulocyte-macrophage colony-stimulating factor has been used in clinic for years,it is routine therapy for breast cancer assistant chemotherapy. In clinical works,we found that the wound of poor healing in the patients whose leucocyte is lower than normal caused by chemotherapy would heal quickly after receiving rhGM-CSF therapy.So we assume whether monocyte or macrophage or GM-CSF can promote vessel formation of flap.Literatures indicate that more and more research is about GM-CSF promoting wound healing recently and most of them show positive results.But there are few research about applying GM-CSF directly on flap and observing its effect on flap survival.So we design DIEP model with GM-CSF macrophage and research its influence on flap survival.It has special significance in clinic.
In th first part of these experiment,we investigate the structure character of rat abdominal flap and improve the havesting process of rat-DIEP flap.We choose the perforator on the layer of rectus abdominis anterior sheath and cut down other blood supply without anatomy of rectus abdominis muscle,and it can shorten the operation time and process more operation in one day.And this will help us degrade the operation,makes the model stable and reproducible.In the first part of the experiment we succeed building a stable rat-DIEP model and form a relatively easy and easy handled process.So rat-DIEP can be a routine model for flap survival research. After model formation,we can record the flap survival progress through general observation and histological examination with HE staining and measure the MVD variety of different time point through immunohistochemistry identified by VWF.We also can analyse the collagen quantity of flap with method of picric-sirius red polarized light.We can trace out the relationship between MVD and collagen quantity in different time during the rat-DIEP flap formation without intervention.
The objective of the second part of experiment is to study the influence of GM-CSF and Mψto the survival rate of rat flap.We directly lavaged the rat's abdomen and gained macrophage after separation and purification.The model rats were divided into 4 groups,which were subcutaneous injection recombined rat GM-CSF group,GM-CSF combining adoptive rat Mψgroup,adoptive rat Mψgroup and saline group.The samples were collected the 7th day after operation,the flap survival area were measured,immunohistochemistry MVD were detected and collagen quantity were examined by Masson staining.Activated Mψcan excrete more than 100 kinds of substance including massive cellular factor which can induce vessel growth directly.In theory,Mψshould promote flap survival,yet in our experiment it shows no increase of flap survival ratio in adoptive rat Mψgroup.In the examination of flap MVD,it has no statistical significance between MψT group and control group. In the collagen quantity examination,we found it was lower in the Mψgroup than the control group(p＜0.05).The reason may be Mψover activate metalloproteinase to lead to prolong the collagen decomposition.On the contrary,the flap survival rate is higher in GM-CSF combining adoptive rat Mψgroup than the control group(p＜0.05) and its MVD and collagen quantity is higher than the control group(p＜0.001).
The conclusion from the second part of the experiment is subcutaneous injection recombined rat GM-CSF and GM-CSF combining adoptive rat Mψcan elevate the survival rate of rat DIEP flap.adoptive rat Mψcannot elevate the survival rate of rat DIEP flap.Recombined rat GM-CSF and GM-CSF combining adoptive rat Mψcan distinctively elevate the MVD and collagen quantity of rat DIEP flap the 7th day after operation.
The objective of the third part of the experiment is to explore the molecular mechanism of recombined rat GM-CSF and GM-CSF combining adoptive rat Mψpromoting rat DIEP flap survival.In the experiment,we test multiple gene expression in the flap we used in the second part with the technique of RT-PCR,including EMMPRIN、MMP2、TIMP1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1、VEGF、EGFR and VEGFR et al.We compared their expression in the flap and discuss the mechanism of promoting flap survival by GM-CSF and GM-CSF combining adoptive rat Mψin gene level.The result showed EMMPRIN、MMP2、CollagenⅠ、EGF和EGFR expression was higher in GM-CSF group than the control group.EMMPRIN、MMP2、TIMP1、CollagenⅠ、CollagenⅢ、EGF、TGF-β1 and EGFR expression in combining GM-CSF+Mψgroup was higher than the control group.EMMPRIN、MMP2、TGF-β1 and EGF expression was high in Mψgroup than the control group. The upregulation the expression of these gene on the molecular level can explain why the flap survival rate was higher in the experiment group.
In conclusion,we find rat DIEP model is a stable and reliable flap study model and recombined rat GM-CSF and GM-CSF combining adoptive rat Mψcan elevate the survival rate of rat DIEP flap.In further research,we find it can upregulate the some gene expression of the flap to promote vessel formation and collagen modeling, it lead to promote flap survival eventually.
引文
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