放射性核素90Sr防治瘢痕的研究

目的 探讨放射性核素^90Sr对人体增生性瘢痕和猪伤口愈合模型超微结构的影响，寻找应用^90Sr治疗瘢痕的最佳时间及有效剂量，为其临床应用提供形态学基础。方法 采用放射性核素^90Sr敷贴器，用200－800cGy和200－4000cGy分别照射临床诊断为增生性瘢痕者的瘢痕和猪创伤愈合模型，用透射电镜观察成纤维细胞超微结构的变化。结果 与对照组相比较，小中剂量（200－600cGy）^90Sr显著促进伤口毛细血管和成纤维细胞增生，细胞功能活跃，胶原纤维排列致密；大剂量（800－2000cGy)^90Sr照射能显著抑制成纤维细胞增生，胶原纤维排列稀疏。结论 临床上可在伤后早期（约2－3d）用小中剂量^90Sr照射，以促进伤口恰愈合；愈合良好的伤口，用大剂量^90Sr照射可防止瘢痕增生；治疗陈旧性、增生性瘢痕或瘢痕疙瘩，^90Sr剂量尖为1000－2000cGy；手术前^90Sr照射瘢痕无价值，而术后配合大剂量^90Sr照射才是防止瘢痕过度增生的有效方法。     

放射治疗兔耳增生性瘢痕的实验研究

目的:研究经过医用高能电子线照射兔耳增生性瘢痕实验模型后,观察伤口愈合的情况、瘢痕愈合后的病理改变及肌动蛋白(ACTIN)和血管生长因子(VEGF)表达变化情况。方法:选用日本大耳白兔18只,在每只兔耳腹侧面制作直径6mm的圆形全层皮肤缺损创面10个。将总计360个缺损创面模型随机分为6组,第1组为空白对照组(3只),其余5组为照射组(各3只)。将照射组每只兔耳随机用200cGy、400cGy、600cGy、800cGy、1000cGy的6Mev电子线照射兔耳缺损创面,照射野周围用铅板防护,观察兔耳缺损创面的愈合情况变化及创面愈合后瘢痕组织进展情况。并于致伤一个月后对实验模型取材,进行光镜、电镜及组织学观察。结果:兔耳腹侧面圆形创面缺损,能产生与人类增生性瘢痕类似的增生块。各照射组,缺损创面愈合延迟。总照射剂量相近的情况下,单次不同照射剂量对增生性瘢痕形成的影响有显著性差异。结论:日本大耳白兔可以形成类似人的增生性瘢痕病理改变,可以用作增生性瘢痕研究的实验动物模型。动物实验证明,医用6Mev高能电子线照射治疗是一种有效的治疗增生性瘫痕的方法,总照射剂量相近的情况下,分5次照射、单次剂量400cGy,为最佳照射剂量。     

手术联合放射性核素90Sr-90Y或曲安奈德治疗兔耳增生性瘢痕的疗效

目的探讨手术联合90Sr90Y（以下简称90Sr）照射或曲安奈德注射治疗增生性瘢痕的最佳方案及安全性。方法将兔耳增生性瘢痕随机分为8组：A组直接行放射性核素90sr照射,B组手术修薄后2d行90sr照射,c组手术修薄后1周行90sr照射,D组直接注射曲安奈德,E组手术修薄后1周注射曲安奈德,F组直接注射生理盐水,G组手术修薄后1周注射生理盐水,H组为空白对照。观察各组的组织学变化。结果（1）90sr照射组（A、B、C组）与曲安奈德注射组（D、E组）成纤维细胞数、胶原纤维面密度值、微血管数、a平滑肌肌动蛋白（a—SMA）阳性颗粒吸光度值均明显低于生理盐水组（F、G组）和空白对照组（H组）;其中B组最明显;A、C、D、E各组差异无统计学意义。（2）90sr照射各组黑色素颗粒面密度值明显低于其他各组,差异有统计学意义（P〈O．05）。（3）90Sr照射各组未发现异型细胞。结论（1）90Sr及曲安奈德可以抑制兔耳增生性瘢痕的增生,二者疗效差异无统计学意义。（2）对增生性瘢痕早期进行90sr干预可取得较好效果。（3）经90sr照射易引起色素脱失,但一般不会引起癌变。     

90Sr治疗增生性瘢痕的基础与临床研究

目的 探讨90Sr防治瘢痕增生的作用机制并观察临床疗效. 方法 用90Sr敷贴器按照0、5、10,15 Gy剂量照射体外培养的人增生性瘢痕Fb.照射后24、48、72 h,流式细胞仪测定细胞周期及凋亡率变化,ELISA法检测细胞培养上清液中Ⅰ型腔原浓度.评价348例增生性瘢痕患者、40例瘢痕疙瘩患者及114例外科手术后瘢痕预防患者应用90Sr照射治疗的效果,并经HE染色对比正常皮肤组织、增生性瘢痕组织、经90SR照射治疗的增生性瘢痕组织中Fb数目.对数据进行单因素方差分析和q检验. 结果 (1)剂量为10、15 Gy的90Sr照射后24、48 h,细胞凋亡率呈逐渐上升趋势,至照射后72 h两者凋亡率相近.剂量为5 Gy的90Sr照射后48 h细胞凋亡率明显高于照射后24 h,但照射后72 h细胞凋亡率迅速下降,与剂量为10、15 Gy时比较差异均有统计学意义(F值均为916.711,P值均小于0.01).(2)照射后24h,90Sr照射剂量为5、10 Gy时,细胞各周期的百分比相近;90Sr照射剂量为15 Gy时,S期细胞明显增多[(48.1±1.0)％,F值均为200.277,P值均小于0.01].剂量为10 Gy及15 Gy的90Sr照射后72 h,细胞明显阻滞在S期,S期细胞百分比分别为(85.7±5.2)％、(73.0±8.4)％,与照射剂量为0 Gy和5 Gy时比较差异均有统计学意义(F值均为111.105,P值均小于0.01).(3)同一照射时相点下,照射剂量越大,Ⅰ型胶原浓度越低(F值为5044.449～8234.423,P值均小于0.01).同一照射剂量下,随着时间推移,Ⅰ型胶原浓度有不同程度的增加(F值为333.395～2973.730,P值均小于0.01).(4)临床病例观察显示,90Sr照射病理性瘢痕或术后瘢痕预防患者后,显效率及有效率累计88.45％.HE染色显示,90Sr照射治疗的人增生性瘢痕Fb数目[每200倍视野(86±20)个]少于未经照射治疗者[每200倍视野(198±65)个,F=208.405,P＜0.05]. 结论 90Sr抑制瘢痕的生长是其对瘢痕Fb和ECM共同作用的结果,且临床疗效显著.     

光动力学疗法对兔耳增生性瘢痕的影响

目的：评价光动力学疗法对兔耳增生性瘢痕的影响。方法：将实验对象随机分成四组,分别为光动力学治疗组、激光治疗组、单纯光敏剂组及对照组,针对瘢痕愈合过程进行干预,观察并检测干预后1月、2月及6月各组的瘢痕增生情况,病理学变化以及成纤维细胞凋亡情况,就各组对瘢痕的影响进行比较、分析和评估。结果：各组均经历了一个损伤至愈合的过程,其中光动力学治疗组瘢痕增生最不明显,成纤维细胞及胶原纤维于损伤初期排列最为紊乱,后期恢复最整齐,伴胶原纤维明显增生,该组成纤维细胞凋亡指标变化最为明显。结论：光动力学治疗能有效预防并治疗增生性瘢痕,尤其是激光能量密度为7.5J/cm2～8.0J/cm2的治疗组效果尤为明显,差异存在统计学意义。     

脉冲染料激光不同治疗周期对兔耳增生性瘢痕成纤维细胞增殖与凋亡的影响

目的：探讨不同治疗周期脉冲染料激光照射对增生性瘢痕动物模型伤口愈合过程中成纤维细胞增殖与凋亡的影响。方法：大耳白兔10只,建立兔耳腹侧面增生性瘢痕模型,对比研究在瘢痕形成过程中不同治疗周期（1周治疗组与2周治疗组）脉冲染料激光照射对兔耳瘢痕成纤维细胞的影响,采用免疫组化方法检测增殖细胞核抗原（PCNA）蛋白表达和细胞凋亡的原位检测。结果：兔耳增生性瘢痕经不同治疗周期（1周治疗组与2周治疗组）脉冲染料激光照射后,按不同时间段取材进行免疫组化染色比较,两组无明显差异。结论：不同治疗周期脉冲染料激光照射均可抑制兔耳增生性瘢痕成纤维细胞的增殖过程,诱导细胞凋亡。但从减轻医生工作强度及减轻病患治疗费用角度考虑,利用脉冲染料激光治疗增生性瘢痕2周一次较为合适。     

595nm激光对兔耳瘢痕成纤维细胞增殖与凋亡的影响

目的：探讨595nmVbeam激光照射对增生性瘢痕动物模型伤口愈合过程中成纤维细胞增殖与凋亡的影响。方法：成年大耳白兔20只,建立兔耳腹侧面增生性瘢痕模型,对比研究在瘢痕形成过程中595nmVbeam激光照射对兔耳瘢痕成纤维细胞的影响,采用免疫组化方法检测增殖细胞核抗原（PCNA）蛋白表达和细胞凋亡的原位检测。结果：兔耳增生性瘢痕经595nmVbeam激光照射后,按不同时间段取材进行免疫组化染色并与对照组比较,高倍镜下观察结果,显示PCNA蛋白表达明显减弱,细胞凋亡增加。结论：595nmVbeam激光照射可抑制兔耳增生性瘢痕成纤维细胞的增殖过程,诱导细胞凋亡。应用595nmVbeam激光预防和治疗瘢痕是可行的。     

外源性碱性成纤维细胞生长因子对创面愈合病理变化的影响

目的:探讨外源性碱性成纤维细胞生长因子(bFGF)在伤口愈合过程中可能的愈合机制以及对瘢痕形成的影响。方法:选用成年健康新西兰兔24只,建立兔耳创面愈合模型96个,随机分为bFGF治疗组和磷酸盐缓冲液(PBS)对照组,观察平均愈合时间、瘢痕体积、组织学变化及超微结构。结果:①bFGF组与对照组愈合时间分别为(18．4±1．6)d、(21．3±1．4)d,两组之间有显著性差异(P＜0．05)。②bFGF组瘢痕体积明显小于对照组,两组间差异有统计学意义(P＜0．01)。③光镜观察,bFGF组在愈合期炎症反应、血管形成及成纤维细胞增殖更明显。在愈合后的瘢痕组织中,胶原纤维排列较规则。对照组炎症反应时间较长,胶原纤维较粗大,排列紊乱。④电镜下可见治疗组成纤维细胞胶原合成持续时间较短。肥大细胞与成纤维细胞紧密接触,调整愈合全过程。后期表皮与真皮间有部分基底膜重建;对照组成纤维细胞合成持续时间较长,未见有基底膜的重建。结论:在伤口愈合过程中,外源性bFGF通过对细胞的调控有效地发挥促愈合作用;同时,通过部分重建基底膜结构,改善瘢痕的形成。     

ALA光动力治疗兔耳增生性瘢痕模型的实验研究

目的：观察ALA光动力学疗法对兔耳增生性瘢痕的影响。方法：建立兔耳增生性瘢痕模型后,将增生性瘢痕块随机分为ALA-光动力学治疗组和对照组。观察ALA对增生性瘢痕微血管、成纤维细胞、胶原纤维的影响。结果：ALA-光动力学治疗后瘢痕厚度显著变薄;微血管及成纤维细胞明显减少;胶原纤维明显稀疏,排列较规则有序。结论：ALA-光动力学治疗能够显著抑制兔耳增生性瘢痕的增生。     

综合疗法治疗体表局限瘢痕86例临床分析

我科自2005年1月～2010年12月，门诊手术治疗各种体表局限瘢痕患者86例，采用瘢痕切除美容外科技术缝合伤口，愈合后伤口涂抹防治瘢痕增生药物，同时行同位素90Sr-90Y 照射治疗取得了良好效果，现报道如下。     

Fibronectin gene expression differs in normal and abnormal human wound healing

The overproduction of fibronectin and type I collagen in keloids and hypertrophic scars implicates altered regulation of extracellular matrix components as an important aspect of these wound healing pathologies. However, little is known about the similarities and differences in extracellular matrix gene expression during normal and abnormal wound healing. This study compared the content of fibronectin messenger RNA and rates of fibronectin protein biosynthesis in fibroblasts derived from normal skin, normal scar, keloid, and hypertrophic scar. Fibronectin expression was enhanced in cells from both normal and abnormal wounds relative to cells from quiescent normal skin. Matched pairs of normal and keloid fibroblasts from the same individuals were also compared, and three of the four pairs showed higher fibronectin expression by the keloid cells at the levels of messenger RNA and protein synthesis. This was consistent with previous studies showing elevated steady state content of fibronectin in keloid cells relative to normal cells from the same individual. Fibronectin messenger RNA and protein content in the tissues from which these cells were derived was examined by in situ hybridization and immunohistochemistry. These studies revealed that in vivo, the steady state content of fibronectin messenger RNA and protein was highest in abnormal wounds, less in most normal scars, and lowest in normal skin. Thus, fibroblasts from keloids and hypertrophic scars overexpressed fibronectin in vivo relative to normal skin and normal scar and retain this characteristic in vitro relative to normal skin. Although normal scars contained little fibronectin protein and messenger RNA, cultured fibroblasts derived from these scars had contents of fibronectin messenger RNA and rates of biosynthesis in vitro similar to those of keloid fibroblasts. This indicates that the fibronectin regulatory pathway in scar fibroblasts is influenced by the tissue environment. These results are discussed with respect to the relationship of fibronectin expression in keloids, hypertrophic scars, and normal wounds in human beings.     

Innervation of normal and hypertrophic human scars and experimental wounds in the rat

The present study was designed to investigate the role of nerve elements in normal and aberrant human wounds, and in experimental rat wound healing model. The innervation of normal and hypertrophic human scars was studied using indirect immunofluorescence labeling with antibodies specific for neurofilament protein. Furthermore, ingrowth of axons into experimental rat wounds was assayed. The results demonstrated that, in contrast to normal wounds, hypertrophic scars were traversed by a high number of bundles of axons. Our results also demonstrated that experimental rat granulation tissue which represented early phases of wound healing attracted axonal growth. To conclude, our findings indicate that normal wound healing is accompanied with innervation of the scars, and that hypertrophy of scars is accompanied with hypertrophy of nerves within the scars. Our results also suggest that aberrations in the innervation of scars may either cause aberrant wound healing, or neural hypertrophy may be a result of disturbed interplay in wound healing mechanisms.     

兔耳解剖特点与成功建立增生性瘢痕模型的相关性实验研究

目的 观察兔耳不同部位的解剖结构特点,探讨不同手术方式以及术后处理方法对兔耳增生性瘢痕形成的影响,为成功建立增生性瘢痕动物模型提供理论依据.方法 新西兰白兔25只,切取5只兔10只耳60份全层组织标本,进行正常组织学观察;20只兔40只耳,每只兔耳腹侧各建立直径为8mm的全层皮肤缺损6个,总计240个创面.其中10只兔120个创面随机分为4组,手术后7d给予不同处理;另外10只兔120个创面术后不做处理.连续观察创面愈合以及瘢痕增生情况6个月,分别于手术后4、8周留取瘢痕组织行病理学检查和测量瘢痕增生指数.结果 正常兔耳不同部位的解剖结构特点不一致;建立兔耳瘢痕模型,部位宜选择在双侧兔耳腹侧内侧缘中、下侣部位,创伤深度宜破坏软骨膜,瘢痕形成率高,瘢痕增生指数高,持续时间长;术后剥痂可促进创面愈合,不利于瘢痕形成与增生.结论 兔耳自身的解剖结构特点与成功建立增生性瘢痕模型有一定的相关性,选择合适的建模部位、合理的创伤深度、术后恰当的处理均可影响瘢痕的形成和增生程度,可以提高增生性瘢痕建模成功率.     

自体富血小板血浆治疗供皮区创面延迟不愈的疗效观察

目的 探讨自体富血小板血浆(platelet-rich plasma,PRP)治疗供皮区延迟不愈创面的疗效.方法 回顾性分析自2016年10月至2019年10月三峡大学人民医院烧伤整形外科收治的7例取皮后延迟不愈创面患者的临床资料.应用PRP凝胶进行治疗后随访6～24个月,观察创面愈合时间及愈后瘢痕增生情况.结果 本组...     

Control of wound contraction. Basic and clinical features

Although a substantial amount of molecular and cellular data have been generated in an effort to understand the process of wound contraction and scar contracture formation, questions remain. What seems apparent is that the myofibroblast is not the only cell that generates contractile forces within wounds, but it does appear to be intrinsically linked to the development of hypertrophic scars. The supposition that the formation of scar contractures is solely the result of a continuation of wound contraction is an oversimplification. Figure 4 provides a model of the possible evolution of contractile forces during the wound healing process and their role in the development of scar contractures. Migration of fibroblasts into and through the extracellular matrix during the initial phase of wound healing, prior to the expression of alpha-SMA, appears to be a fundamental component of wound contraction. During this migration, the pulling of collagen fibrils into a streamlined pattern in their wake, and the associated production of collagenase, may facilitate a more normal arrangement of collagen. Once the wound has been repopulated and the chemotactic gradient that was established by inflammatory cells is decreased, fibroblast migration will cease. It is at this point that myofibroblasts appear and play a key role in the production of hypertrophic scars, given that their prolonged presence and over-representation are hallmarks of this pathology. One of the pivotal differences between wounds that proceed to normal scar compared with those that develop hypertrophic scars and scar contractures may be a lack (or late induction) of myofibroblast apoptotic cell death. The combined contribution of fibroblasts and myofibroblasts to abnormal extracellular matrix protein production results in an excessive and rigid scar. The isometric application of contractile forces by myofibroblasts probably contributes to the formation of the whorls, nodules, and scar contractures characteristic of hypertrophic scars. Because the prolonged presence of myofibroblasts, producing an imbalance in extracellular matrix proteins and proteases, probably exacerbates hypertrophic scars and wound contraction, accelerating the rate of apoptotic cell death to reduce the cell number to that seen in normal scar may be a useful strategy for providing effective and efficient treatment of scar contracture.     

Double‐edged effects of neuropeptide substance P on repair of cutaneous trauma

To explore further the role of substance P (SP) in wound healing and scar formation, SP concentrations in wounds of scalded rats were assayed. Expressions of apoptosis‐associated genes in fibroblasts cultured with SP were detected. SP concentrations in superficial wounds increased earlier than those in deep wounds. SP was associated with an increased proliferation and a decreased apoptosis of fibroblasts. It had a greater influence on keloid fibroblasts than on hypertrophic scar fibroblasts by elevating the expression of proliferating cell nuclear antigen and BCL‐2 in fibroblasts. Spantide completely suppressed the effects of SP on hypertrophic scar fibroblasts, and partly inhibited its effects on keloid scar fibroblasts. SP may play an important role in wound healing by promoting wound fibroblast proliferation and inhibiting apoptosis. It may also participate in pathological scar formation by modulating the expression of apoptosis‐associated genes. SP is postulated to play a dual role in wound repair.     

Intravenous curcumin efficacy on healing and scar formation in rabbit ear wounds under nonischemic,ischemic, and ischemia–reperfusion conditions

Curcumin, a spice found in turmeric, is widely used in alternative medicine for its purported anti‐inflammatory and antioxidant activities. The goal of this study was to test the curcumin efficacy on rabbit ear wounds under nonischemic, ischemic, and ischemia–reperfusion conditions. Previously described models were utilized in 58 New Zealand White rabbits. Immediately before wounding, rabbits were given intravenous crude or pure curcumin (6 μg/kg, 30 μg/kg, or 60 μg/kg) dissolved in 1% ethanol. Specimens were collected at 7–8 days to evaluate the effects on wound healing and at 28 days to evaluate the effects on hypertrophic scarring. Student's t test was applied to screen difference between any treatment and control group, whereas analysis of variance was applied to further analyze for all treatment groups in aggregate in some specific experiments. Treatment with crude curcumin suggested accelerated wound healing that reached significance for reepithelialization in lower and medium doses and granulation tissue formation in lower dose. Purified curcumin became available and was used for all later experiments. Treatment with pure curcumin suggested accelerated wound healing that reached significance for reepithelialization in lower and medium doses and granulation tissue formation in lower dose. Treatment with pure curcumin significantly promoted nonischemic wound healing in a dose–response fashion compared with controls as judged by increased reepithelialization and granulation tissue formation. Improved wound healing was associated with significant decreases in pro‐inflammatory cytokines interleukin (IL)‐1 and IL‐6 as well as the chemokine IL‐8. Curcumin also significantly reduced hypertrophic scarring. The effects of curcumin were examined under conditions of impaired healing including ischemic and ischemia–reperfusion wound healing, and beneficial effects were also seen, although the dose response was less clear. Systemically administrated pure curcumin significantly promotes nonischemic wound healing and reduces hypertrophic scarring. Improvements in wound healing were associated with decreased inflammatory markers in wounds. Further study is needed to optimize dosing in ischemic and ischemia–reperfusion wound healing. In aggregate, the studies strongly support the systemic administration of curcumin to improve wound healing.