體外沖擊波抑制兔耳增生性瘢痕的實驗研究
發(fā)布時間：2018-08-24 13:04
【摘要】：盡管在過去數(shù)年間診療技術方面取得了突飛猛進的發(fā)展，增生性瘢痕(HS)的預防和治療仍是臨床醫(yī)生亟待解決的難題之一。HS不僅嚴重影響機體功能和美觀，還可因疼痛（或觸痛）和感覺異常（瘙癢、燒灼感）導致患者睡眠障礙、焦慮、抑郁，顯著降低患者的生活質量。隨著社會經濟水平和人們對自我形象的注重，HS的防治受到越來越多的關注。研究HS的預防和治療對提高患者的生活質量具有重要意義。 目前關于HS形成的機制主要包括：細胞因素、細胞因子因素、微循環(huán)因素、免疫因素、基因表達因素、創(chuàng)面因素等。HS的治療目標是恢復功能，緩解癥狀，改善外觀和預防復發(fā)。目前已有多種方法用于增生性瘢痕的治療，如外用或局部注射藥物、手術治療、物理治療（如激光療法、加壓療法、按摩等）、放射治療、冷凍療法、基因治療等。雖然可選擇的方法多樣，然而上述各種療法卻存在不同程度的不足之處，如手術的創(chuàng)傷性，脈沖染料激光可引起局部色素改變和對較厚的HS效果不理想。瘢痕內藥物注射除可引起疼痛和色素改變外，還可引起注射部位的水皰、潰瘍和壞死。加壓療法可因高壓力引起的不適感、限制活動和影響外觀而使患者依從性下降。而冰凍療法治療瘢痕可引起色素缺失，放射療法則存在放射性皮炎和潛在的致癌可能。因此，尋求一種無創(chuàng)、安全、有效和經濟的方法治療增生性瘢痕具有重要意義。 體外沖擊波療法(ESWT)具有無創(chuàng)、安全、操作簡便等優(yōu)勢，目前已廣泛應用于泌尿系和消化系結石、骨折不愈合或延遲愈合、肩周炎、肱骨外上髁炎慢性軟組織疾病。此外，ESWT還廣泛用于改善組織缺血、治療燒傷和糖尿病足、提高皮膚/皮瓣移植成活率等方面。ESWT的作用機制包括：促進創(chuàng)面血管生成，增加組織血流供應，抑制早期的炎癥反應，促進間充質干細胞和內皮祖細胞趨至創(chuàng)面，刺激創(chuàng)面細胞增殖、分化和再生，減輕創(chuàng)面細菌定植等。 雖然ESWT在急慢性創(chuàng)面的治療中顯示出優(yōu)越性，然而關于其對瘢痕治療效果的研究卻十分有限。本研究中，首先制備兔耳腹側面全層組織缺損模型，造模21天后HS形成（經病理切片證實）。將白兔隨機分為低能量ESWT組（能流密度0.1mJ/mm2）、高能量ESWT組（能流密度0.2mJ/mm2）和對照組。ESWT組白兔分別于造模成功后第1、4、9、14、21、28天給予不同能流密度ESWT處理，對照組未予任何處置。分別于第一次ESWT處理后1、4、7、10、14、21、28、35天觀察并記錄瘢痕顏色、質地變化，同時采集組織樣本，通過下述分子生物學和病理學手段檢測以下指標： 1.通過Antera3D成像系統(tǒng)測量瘢痕直徑、面積、隆起體積、質地、皺褶、黑色素、血紅素的變化； 2.病理學染色觀察ESWT對HS組織學的影響： HE染色觀察瘢痕增生指數(shù)（hypertrophic index, HI）、成纖維細胞（Fb）形態(tài)和密度、毛細血管數(shù)及炎性細胞浸潤情況；Masson染色明確膠原纖維分布情況； 3.瘢痕增殖和分化的研究：逆轉錄-聚合酶鏈式反應(RT-PCR)檢測增殖細胞核抗原(PCNA)和α-平滑肌肌動蛋白(α-SMA)的基因表達情況；免疫組化染色明確二者在細胞內表達情況； 4.對轉化生長因子-β1（TGF-β1）/Smad通路影響的研究：RT-CPR分別檢測TGF-β1、Smad2、Smad3的基因表達水平；酶聯(lián)免疫吸附試驗檢測TGF-β1、Smad2、Smad3、Smad7的蛋白表達水平； 實驗主要結果： 一、大體觀察ESWT處理后3周，兩ESWT組瘢痕顏色開始并略淡于對照組，并且變得扁平和軟化。4周時，對照組瘢痕開始退變軟化，但仍可見明顯凸起，顏色較治療組仍發(fā)紅。低能量ESWT組和高能量ESWT組瘢痕變平，硬度與色澤較對照組減輕。兩ESWT組間相比無明顯差別。 二、 Antera3D檢測結果 1.瘢痕皺褶：與對照組相比，低能量ESWT組處理14天、高能量ESWT組處理21天后瘢痕皺褶開始顯著減少（t=-2.195, P=0.042；t=-2.267, P=0.037），并可持續(xù)至第四周。 2.瘢痕質地：與對照組相比，低能量ESWT組處理4周后瘢痕質地出現(xiàn)明顯改善（t=-2.788, P=0.014）。高能量ESWT組處理后瘢痕質地未見明顯改善。 3.瘢痕直徑、面積、隆起體積和黑色素：與對照組相比，低能量ESWT組和高能量ESWT組對瘢痕上述參數(shù)均未見有明顯影響。 4.瘢痕血色素：與對照組相比，低能量ESWT組處理兩周后瘢痕血色素開始明顯下降（t=-2.361, P=0.040）；處理3周后，低能量ESWT組和高能量ESWT組與對照組瘢痕血色素相比均存在顯著差異（t=-2.474, P=0.043；t=-2.838, P=0.025），這一差異在第四周仍可見到。 三、兔耳瘢痕組織的組織病理學檢測 1. HE染色1周：各組間炎細胞浸潤、微血管增生、HI無顯著差異。低能量ESWT組與高能量ESWT組、對照組相比Fb密度均顯著降低，高能量ESWT組與對照組相比Fb密度也顯著降低。2周-5周：與對照組相比，ESWT處理組HS真皮層較對照組變薄，炎細胞浸潤減輕，微血管和膠原纖維較對照組數(shù)量減少，HI和Fb密度均顯著降低, ESWT組間相比無顯著性差異。 2. Masson染色1周：各組間無明顯差別。2周-5周：對照組膠原纖維數(shù)量多，排列不整齊，可見漩渦狀結構和膠原結節(jié)；ESWT組膠原束較細，排列較對照組疏松和規(guī)則，大致呈平行于表皮的水平方向。兩ESWT組間未見明顯差別。 四、 ESWT對HS增殖和分化的影響 1.對PCNA和α-SMA組織病理學檢測低能量ESWT早期即可顯著抑制HS組織中PCNA的表達；高能量ESWT在后期（4周）也可降低細胞內PCNA的表達水平，兩組間相比無明顯差別。無論是低能量ESWT還是高能量ESWT均可顯著降低細胞內α-SMA的表達水平，并且在低能量ESWT組更明顯。 2.對PCNA和α-SMA mRNA表達的影響與對照組相比，低能量ESWT和高能量ESWT組對HS中PCNA mRNA的表達均未見明顯影響。低能量ESWT可顯著降低HS中α-SMA mRNA的表達水平，高能量ESWT與對照組相比無明顯差別。 五、 ESWT對TGF-β/Smad信號通路的影響 1.對TGF-β/Smad信號通路mRNA表達的影響低能量ESWT和高能量ESWT對TGF-β1mRNA的表達均未見顯著影響。此外，低能量ESWT對Smad2mRNA的表達亦未見明顯影響，但可顯著抑制Smad3mRNA的表達。高能量ESWT則可顯著上調Smad2和Smad3mRNA的表達水平。 2.對TGF-β/Smad信號通路蛋白表達的影響低能量ESWT可顯著抑制Smad3的表達，對TGF-β1、Smad2和Smad7蛋白含量未見顯著影響。高能量ESWT對TGF-β1、Smad2、Smad3和Smad7蛋白含量均未見顯著影響。 結論： 1. ESWT無創(chuàng)、安全、操作方便且耐受性良好。不同能量ESWT均可軟化HS，改善其色澤，減少瘢痕皺褶，但對瘢痕直徑、面積和黑色素水平均未見明顯影響。此外，低能量ESWT還可顯著改善瘢痕粗糙度。病理學檢查顯示，不同能流密度ESWT均可減輕炎細胞浸潤程度，減少Fb數(shù)目和密度，，降低瘢痕厚度，改善膠原纖維排列。 2.低能量ESWT可早期抑制HS組織細胞中Smad3信號轉導因子和α-SMA mRNA和蛋白表達水平。高能量ESWT在后期雖可顯著抑制α-SMA和PCNA mRNA和蛋白的表達水平，然而也可顯著升高具有促進瘢痕形成作用的Smad2和Smad3mRNA和蛋白的表達水平，高能量ESWT對瘢痕的影響有待于進一步研究。
[Abstract]:Despite the rapid development of diagnostic and therapeutic techniques in the past few years, the prevention and treatment of hypertrophic scar (HS) remains one of the most pressing problems for clinicians. HS not only seriously affects the body's function and aesthetics, but also causes sleep disorders, anxiety, depression and symptoms of pain (or tenderness) and sensory abnormalities (itching, burning). With the social and economic level and people's attention to self-image, more and more attention has been paid to the prevention and treatment of HS.
At present, the mechanism of HS formation mainly includes cell factor, cytokine factor, microcirculation factor, immune factor, gene expression factor, wound factor and so on. The aim of HS treatment is to restore function, relieve symptoms, improve appearance and prevent recurrence. Surgical treatment, physical therapy (such as laser therapy, compression therapy, massage, etc.), radiation therapy, cryotherapy, gene therapy, and so on. Although there are a variety of options, the above-mentioned treatments have different degrees of inadequacies, such as surgical trauma, pulsed dye laser can cause local pigment changes and relatively thick HS effect is not satisfactory. In addition to causing pain and pigmentation changes, intrascar drug injections can also cause blisters, ulcers and necrosis at the injection site. Compression therapy can cause discomfort due to high pressure, restrict activity and affect appearance and reduce patient compliance. Therefore, it is of great significance to seek a non-invasive, safe, effective and economical treatment for hypertrophic scars.
Extracorporeal shock wave therapy (ESWT) has the advantages of noninvasiveness, safety and easy operation. It has been widely used in urinary and digestive calculi, nonunion or delayed union of fractures, periarthritis of shoulder, and chronic soft tissue diseases of external epicondylitis of humerus. The mechanisms of ESWT include promoting wound angiogenesis, increasing tissue blood supply, inhibiting early inflammatory reaction, promoting mesenchymal stem cells and endothelial progenitor cells to the wound, stimulating wound cell proliferation, differentiation and regeneration, and reducing bacterial colonization.
Although ESWT has shown superiority in the treatment of acute and chronic wounds, the research on its therapeutic effect on scars is very limited. In this study, a rabbit model of ventral full-thickness tissue defect was established, and HS was formed 21 days after modeling (confirmed by pathological section). The rabbits were randomly divided into low-energy ESWT group (energy flow density 0.1mJ/mm2) and high-energy ESWT group (energy flow density 0.1mJ/mm2). The rabbits in ESWT group were treated with different energy flow density ESWT on the first, fourth, nineteen, fourteen, twenty-one and twenty-eight days after successful modeling, while the rabbits in control group were not treated with any treatment. Molecular biology and pathology were used to detect the following indicators:
1. The scar diameter, area, bulge volume, texture, wrinkles, melanin and heme were measured by Antera 3D imaging system.
2. Histological changes of HS were observed by pathological staining: HE staining was used to observe the hypertrophic index (HI), fibroblast (Fb) morphology and density, capillary number and inflammatory cell infiltration; Masson staining was used to determine the distribution of collagen fibers.
3. Study on scar proliferation and differentiation: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression of proliferating cell nuclear antigen (PCNA) and alpha-smooth muscle actin (alpha-SMA); immunohistochemical staining was used to determine the expression of PCNA and alpha-SMA in the cells.
4. Effects of transforming growth factor-beta 1 (TGF-beta 1) / Smad pathway: TGF-beta 1, Smad2, Smad3 gene expression levels were detected by RT-CPR, and TGF-beta 1, Smad2, Smad3, Smad7 protein expression levels were detected by enzyme-linked immunosorbent assay (ELISA).
Main results of the experiment are as follows:
First, after 3 weeks of ESWT treatment, the scar color of the two ESWT groups began to fade slightly, and became flat and softened. At 4 weeks, the scar of the control group began to degenerate and soften, but the color of the control group was still redder than that of the treatment group. The scar of the low-energy ESWT group and the high-energy ESWT group flattened, and the hardness and color of the two ESWT groups were lighter than that of the control group. There is no obvious difference between them.
Two, Antera3D test results
1. Cicatricial folds: Compared with the control group, the low-energy ESWT group treated for 14 days, the high-energy ESWT group treated for 21 days began to significantly reduce the cicatricial folds (t = - 2.195, P = 0.042; t = - 2.267, P = 0.037), and lasted until the fourth week.
2. Scar texture: Compared with the control group, the low-energy ESWT group showed significant improvement (t =-2.788, P =0.014) after 4 weeks of treatment. The high-energy ESWT group showed no significant improvement in the scar texture.
3. Scar diameter, area, bulge volume and melanin: Compared with the control group, low-energy ESWT group and high-energy ESWT group had no significant effect on the above parameters of scar.
4. Scar hemoglobin: Compared with the control group, the low-energy ESWT group began to decrease significantly after two weeks of treatment (t = - 2.361, P = 0.040); after three weeks of treatment, the low-energy ESWT group and high-energy ESWT group were significantly different from the control group in scar hemoglobin (t = - 2.474, P = 0.043; t = - 2.838, P = 0.025), the difference was still acceptable at the fourth week. See.
Three, histopathological examination of rabbit ear scar tissue.
1. HE staining for 1 week: There was no significant difference in inflammatory cell infiltration, microvascular proliferation and HI among the groups. The density of Fb in low-energy ESWT group and high-energy ESWT group was significantly lower than that in the control group. The density of Fb in high-energy ESWT group was also significantly lower than that in the control group. Compared with the control group, the number of microvessels and collagen fibers decreased, and the density of HI and Fb decreased significantly. There was no significant difference between the ESWT groups.
2. Masson staining for 1 week: there was no significant difference between the groups. 2 weeks to 5 weeks: the number of collagen fibers in the control group was large, arranged irregularly, and there were vortex-like structures and collagen nodules. The collagen bundles in the ESWT group were finer, looser and more regular than those in the control group, and were roughly parallel to the epidermis.
Four, the effect of ESWT on proliferation and differentiation of HS.
1. PCNA and alpha-SMA histopathological examination showed that low-energy ESWT could significantly inhibit the expression of PCNA in HS tissues at the early stage, and high-energy ESWT could also reduce the expression of PCNA in HS cells at the late stage (4 weeks), there was no significant difference between the two groups. In low energy ESWT group, it is more obvious.
2. Compared with the control group, low energy ESWT and high energy ESWT groups had no significant effect on the expression of PCNA mRNA in HS. Low energy ESWT could significantly reduce the expression of alpha-SMA mRNA in HS, and high energy ESWT had no significant difference compared with the control group.
Five, the effect of ESWT on TGF- beta /Smad signaling pathway.
1. The effect of low-energy ESWT and high-energy ESWT on the expression of TGF-beta 1 mRNA was not significant. In addition, low-energy ESWT had no significant effect on the expression of Smad2 mRNA, but could significantly inhibit the expression of Smad3 mRNA. High-energy ESWT could significantly up-regulate the expression of Smad2 and Smad3 mRNA.
2. The expression of Smad3 was significantly inhibited by low-energy ESWT, but not by TGF-beta 1, Smad2 and Smad7. High-energy ESWT had no significant effect on the contents of TGF-beta 1, Smad2, Smad3 and Smad7.
Conclusion:
1. ESWT is noninvasive, safe, easy to operate and well tolerated. Different energy ESWT can soften HS, improve its color and reduce scar folds, but has no significant effect on scar diameter, area and melanin level. In addition, low energy ESWT can significantly improve scar roughness. Pathological examination shows that different possible flow density ESWT can alleviate inflammation. The degree of cell infiltration can reduce the number and density of Fb, reduce the thickness of scar and improve the arrangement of collagen fibers.
2. Low-energy ESWT can inhibit the expression of Smad3 signal transduction factor and alpha-SMA mRNA and protein in HS cells at an early stage. High-energy ESWT can significantly inhibit the expression of alpha-SMA and PCNA mRNA and protein at a later stage, but it can also significantly increase the expression of Smad 2 and Smad3 mRNA and protein, which can promote scar formation. The effect of WT on scar remains to be further studied.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R622
本文編號：2200905
[Abstract]:Despite the rapid development of diagnostic and therapeutic techniques in the past few years, the prevention and treatment of hypertrophic scar (HS) remains one of the most pressing problems for clinicians. HS not only seriously affects the body's function and aesthetics, but also causes sleep disorders, anxiety, depression and symptoms of pain (or tenderness) and sensory abnormalities (itching, burning). With the social and economic level and people's attention to self-image, more and more attention has been paid to the prevention and treatment of HS.
At present, the mechanism of HS formation mainly includes cell factor, cytokine factor, microcirculation factor, immune factor, gene expression factor, wound factor and so on. The aim of HS treatment is to restore function, relieve symptoms, improve appearance and prevent recurrence. Surgical treatment, physical therapy (such as laser therapy, compression therapy, massage, etc.), radiation therapy, cryotherapy, gene therapy, and so on. Although there are a variety of options, the above-mentioned treatments have different degrees of inadequacies, such as surgical trauma, pulsed dye laser can cause local pigment changes and relatively thick HS effect is not satisfactory. In addition to causing pain and pigmentation changes, intrascar drug injections can also cause blisters, ulcers and necrosis at the injection site. Compression therapy can cause discomfort due to high pressure, restrict activity and affect appearance and reduce patient compliance. Therefore, it is of great significance to seek a non-invasive, safe, effective and economical treatment for hypertrophic scars.
Extracorporeal shock wave therapy (ESWT) has the advantages of noninvasiveness, safety and easy operation. It has been widely used in urinary and digestive calculi, nonunion or delayed union of fractures, periarthritis of shoulder, and chronic soft tissue diseases of external epicondylitis of humerus. The mechanisms of ESWT include promoting wound angiogenesis, increasing tissue blood supply, inhibiting early inflammatory reaction, promoting mesenchymal stem cells and endothelial progenitor cells to the wound, stimulating wound cell proliferation, differentiation and regeneration, and reducing bacterial colonization.
Although ESWT has shown superiority in the treatment of acute and chronic wounds, the research on its therapeutic effect on scars is very limited. In this study, a rabbit model of ventral full-thickness tissue defect was established, and HS was formed 21 days after modeling (confirmed by pathological section). The rabbits were randomly divided into low-energy ESWT group (energy flow density 0.1mJ/mm2) and high-energy ESWT group (energy flow density 0.1mJ/mm2). The rabbits in ESWT group were treated with different energy flow density ESWT on the first, fourth, nineteen, fourteen, twenty-one and twenty-eight days after successful modeling, while the rabbits in control group were not treated with any treatment. Molecular biology and pathology were used to detect the following indicators:
1. The scar diameter, area, bulge volume, texture, wrinkles, melanin and heme were measured by Antera 3D imaging system.
2. Histological changes of HS were observed by pathological staining: HE staining was used to observe the hypertrophic index (HI), fibroblast (Fb) morphology and density, capillary number and inflammatory cell infiltration; Masson staining was used to determine the distribution of collagen fibers.
3. Study on scar proliferation and differentiation: Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the gene expression of proliferating cell nuclear antigen (PCNA) and alpha-smooth muscle actin (alpha-SMA); immunohistochemical staining was used to determine the expression of PCNA and alpha-SMA in the cells.
4. Effects of transforming growth factor-beta 1 (TGF-beta 1) / Smad pathway: TGF-beta 1, Smad2, Smad3 gene expression levels were detected by RT-CPR, and TGF-beta 1, Smad2, Smad3, Smad7 protein expression levels were detected by enzyme-linked immunosorbent assay (ELISA).
Main results of the experiment are as follows:
First, after 3 weeks of ESWT treatment, the scar color of the two ESWT groups began to fade slightly, and became flat and softened. At 4 weeks, the scar of the control group began to degenerate and soften, but the color of the control group was still redder than that of the treatment group. The scar of the low-energy ESWT group and the high-energy ESWT group flattened, and the hardness and color of the two ESWT groups were lighter than that of the control group. There is no obvious difference between them.
Two, Antera3D test results
1. Cicatricial folds: Compared with the control group, the low-energy ESWT group treated for 14 days, the high-energy ESWT group treated for 21 days began to significantly reduce the cicatricial folds (t = - 2.195, P = 0.042; t = - 2.267, P = 0.037), and lasted until the fourth week.
2. Scar texture: Compared with the control group, the low-energy ESWT group showed significant improvement (t =-2.788, P =0.014) after 4 weeks of treatment. The high-energy ESWT group showed no significant improvement in the scar texture.
3. Scar diameter, area, bulge volume and melanin: Compared with the control group, low-energy ESWT group and high-energy ESWT group had no significant effect on the above parameters of scar.
4. Scar hemoglobin: Compared with the control group, the low-energy ESWT group began to decrease significantly after two weeks of treatment (t = - 2.361, P = 0.040); after three weeks of treatment, the low-energy ESWT group and high-energy ESWT group were significantly different from the control group in scar hemoglobin (t = - 2.474, P = 0.043; t = - 2.838, P = 0.025), the difference was still acceptable at the fourth week. See.
Three, histopathological examination of rabbit ear scar tissue.
1. HE staining for 1 week: There was no significant difference in inflammatory cell infiltration, microvascular proliferation and HI among the groups. The density of Fb in low-energy ESWT group and high-energy ESWT group was significantly lower than that in the control group. The density of Fb in high-energy ESWT group was also significantly lower than that in the control group. Compared with the control group, the number of microvessels and collagen fibers decreased, and the density of HI and Fb decreased significantly. There was no significant difference between the ESWT groups.
2. Masson staining for 1 week: there was no significant difference between the groups. 2 weeks to 5 weeks: the number of collagen fibers in the control group was large, arranged irregularly, and there were vortex-like structures and collagen nodules. The collagen bundles in the ESWT group were finer, looser and more regular than those in the control group, and were roughly parallel to the epidermis.
Four, the effect of ESWT on proliferation and differentiation of HS.
1. PCNA and alpha-SMA histopathological examination showed that low-energy ESWT could significantly inhibit the expression of PCNA in HS tissues at the early stage, and high-energy ESWT could also reduce the expression of PCNA in HS cells at the late stage (4 weeks), there was no significant difference between the two groups. In low energy ESWT group, it is more obvious.
2. Compared with the control group, low energy ESWT and high energy ESWT groups had no significant effect on the expression of PCNA mRNA in HS. Low energy ESWT could significantly reduce the expression of alpha-SMA mRNA in HS, and high energy ESWT had no significant difference compared with the control group.
Five, the effect of ESWT on TGF- beta /Smad signaling pathway.
1. The effect of low-energy ESWT and high-energy ESWT on the expression of TGF-beta 1 mRNA was not significant. In addition, low-energy ESWT had no significant effect on the expression of Smad2 mRNA, but could significantly inhibit the expression of Smad3 mRNA. High-energy ESWT could significantly up-regulate the expression of Smad2 and Smad3 mRNA.
2. The expression of Smad3 was significantly inhibited by low-energy ESWT, but not by TGF-beta 1, Smad2 and Smad7. High-energy ESWT had no significant effect on the contents of TGF-beta 1, Smad2, Smad3 and Smad7.
Conclusion:
1. ESWT is noninvasive, safe, easy to operate and well tolerated. Different energy ESWT can soften HS, improve its color and reduce scar folds, but has no significant effect on scar diameter, area and melanin level. In addition, low energy ESWT can significantly improve scar roughness. Pathological examination shows that different possible flow density ESWT can alleviate inflammation. The degree of cell infiltration can reduce the number and density of Fb, reduce the thickness of scar and improve the arrangement of collagen fibers.
2. Low-energy ESWT can inhibit the expression of Smad3 signal transduction factor and alpha-SMA mRNA and protein in HS cells at an early stage. High-energy ESWT can significantly inhibit the expression of alpha-SMA and PCNA mRNA and protein at a later stage, but it can also significantly increase the expression of Smad 2 and Smad3 mRNA and protein, which can promote scar formation. The effect of WT on scar remains to be further studied.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R622
【參考文獻】
相關期刊論文 前10條
1 沈華;沈尊理;王永春;黃一雄;張兆峰;賈萬新;;瘢痕內切除后即時放療治療瘢痕疙瘩臨床分析[J];中國美容醫(yī)學;2009年01期
2 高正君;徐靖宏;姚航平;;瘢痕疙瘩與增生性瘢痕基因的異同[J];中國美容醫(yī)學;2009年01期
3 章慶國,林鶴,冷永成,呂洛;轉化生長因子β_3對人增生性瘢痕成纖維細胞Ⅰ、Ⅲ型膠原表達的影響[J];東南大學學報(醫(yī)學版);2002年01期
4 陳鵬輝;楊冰;馬尚清;董徐斌;樊竹;陳幼楠;馬文珠;;中醫(yī)抑制增生性瘢痕的研究現(xiàn)狀[J];北京中醫(yī)藥大學學報(中醫(yī)臨床版);2013年03期
5 陳璧,賈赤宇,湯朝武,胡大海,丁國斌;堿性成纖維細胞生長因子對增生性瘢痕的作用[J];中華普通外科雜志;2002年01期
6 王西樵;陸樹良;毛志剛;劉英開;;增生性瘢痕中血管內皮細胞生物學功能的研究[J];中華燒傷雜志;2007年03期
7 陳偉,付小兵,王海濱,孫同柱,周崗,李海紅 ,盛志勇;增生性瘢痕形成和成熟過程中轉化生長因子-β1及下游信號分子的基因表達變化[J];中華實驗外科雜志;2005年06期
8 邱林;金先慶;田曉菲;傅躍先;;正常皮膚和瘢痕組織TGF-β_1的表達及膠原構成與年齡相關性研究[J];中華小兒外科雜志;2006年08期
9 胡振富 ,羅力生 ,羅盛康;病理性瘢痕中c-myc、c-fos和ras原癌基因表達的實驗研究[J];中華整形外科雜志;2002年03期
10 曹毅;郭建輝;陶茂燦;;中藥制劑對兔耳增生性瘢痕組織的影響[J];中華中醫(yī)藥學刊;2008年01期
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