P物质对肉芽组织成纤维细胞表皮生长因子的表达调控及其意义

目的 探讨感觉神经肽P物质(SP)对离体培养的肉芽组织成纤维细胞表皮生长因子(EGF)表达的调控作用及特点。方法 采用甲醛注射的方法造成Wistar大鼠局部无菌性炎性反应，提取肉芽组织进行成纤维细胞原代培养；采用逆转录—聚合酶链反应(RT—PCR)方法检测SP对肉芽组织成纤维细胞EGF基因表达的调控作用，观察时间及剂量—效应关系；采用Western-blotting方法检测EGF蛋白表达情况，观察时间及剂量—效应关系。结果 10^-7mol/L SP可诱导成纤维细胞EGF mRNA的表达，在作用后6h与对照组比，差异有显著性(P＜0．01)；SP在10^-8-10^-6mol/L范围内可以显著促进成纤维细胞EGF mRNA表达，在10^-7mol/L达到峰值，10^-5mol/L时与对照组差异无显著性(P＞0．05)。10^-7mol/L SP作用12h后可检测到EGF蛋白明显表达增强(P＜0．01)，24h达高峰，48h后逐渐有所回落。SP在在10^-8--10^-5mol/L范围可诱导EGF蛋白的表达，均在10^-7mol/L剂量点达到峰值(P＜0．01)。结论 SP可诱导肉芽组织成纤维细胞EGF基因和蛋白的表达，且呈现出一定的时间和剂量特点，在SP调控创伤愈合的作用中具有重要意义。     

P物质与表皮干细胞联用对糖尿病大鼠创面愈合与神经再生的影响

目的 观察感觉神经肽P物质与表皮干细胞(ESC)联合应用对糖尿病大鼠创面愈合与神经再生的作用. 方法 分离培养SD大鼠ESC(经鉴定),接种于羊膜滋养层上构建羊膜-ESC备用.选择48只糖尿病模型大鼠,每只背部制作4个全层皮肤缺损创面.按随机抽签法将此192个创面分为ESC+P物质组、ESC组、P物质组、对照组,每组48个创面.ESC+P物质组和ESC组创面均移植羊膜-ESC,P物质组、对照组创面移植羊膜.移植后,ESC+P物质组、P物质组在创周及创面中央注射1×10-7 mol/L的P物质250μL,ESC组、对照组在创周及创面中央注射PBS 250μL作对照,各组每日注射2次,连用4d.于大鼠伤后4、7、10、14、17、23 d,观察并计算创面愈合率(每时相点8个创面),HE染色观察创面组织结构改变.伤后4、7、10 d,行Masson染色观察创面组织总胶原分布,免疫组织化学染色观察Ⅰ、Ⅲ型胶原沉积量.伤后14、23 d,用免疫组织化学染色法观察创面组织中蛋白基因产物9.5(PGP 9.5)及P物质阳性神经纤维分布情况.对数据行单因素方差分析和t检验. 结果(1)ESC+P物质组伤后14 d创面愈合率达100.0％,明显早于ESC组、P物质组、对照组完全愈合时间(伤后17、17、23 d).HE染色显示ESC+P物质组创面愈合质量明显优于其余3组.(2)伤后10 d,ESC+P物质组与P物质组创面组织中胶原着色深、面积广;其余2组胶原染色较浅、面积较小.随着伤后时间推移,各组创面Ⅰ型胶原沉积量逐渐升高,Ⅲ型胶原沉积量逐渐下降.伤后4、7、10 d,ESC+P物质组Ⅰ型胶原沉积量明显高于ESC组(t值分别为32.72、118.21、26.71,P值均小于0.01)和对照组(t值分别为44.37、22 76、30.32,P值均小于0.01);ESC+P物质组与P物质组水平相对接近.伤后4、7、10d,ESC+P物质组创面Ⅲ型胶原沉积量明显高于ESC组(t值分别为32.27、28 68、14.51,P值均小于0.01)和对照组(t值分别为35 68、22.52、22 24,P值均小于0.01).(3)ESC +P物质组与P物质组创面组织中有大量PGP 9.5和P物质阳性神经纤维再生,创面深层部分神经纤维末梢向表皮延伸.ESC组、对照组仅见创面深层有少量PGP 9.5和P物质阳性神经纤维,且未向表皮延伸.伤后14、23 d,ESC+P物质组创面PGP 9.5阳性神经纤维面积占(3.86±0.25)％、(7 03±0.28)％,明显高于ESC组[(1.48±0.30)％、(3.01±0 43)％,t值分别为23 95、30 27,P值均小于0.01]和对照组[(1 46±0 23)％、(2.84±0.29)％,t值分别为27.35、40.32,P值均小于0.01].伤后14、23 d,ESC+P物质组创面P物质阳性神经纤维面积占(2.01±0 14)％、(1.19±0 11)％,明显高于ESC组[(0.85±0 17)％、(1.34±0 21)％,t值分别为20.50、2.60,P＜0.05或P＜0.01]和对照组[(0.74 ±0.15)％、( 1.30 ±0.17)％,t值分别为23 98、2.41,P＜0.05或P＜0.01]. 结论 感觉神经肽P物质和ESC联合应用,可以有效促进糖尿病大鼠创面愈合与神经再生.     

An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor

Various studies have shown that chitosan is effective in promoting wound healing. In this study, we aimed to develop an effective chitosan gel formulation containing epidermal growth factor (EGF), and to determine the effect on healing of second-degree burn wounds in rats. Ten micrograms per millilitre EGF in 2% chitosan gel was prepared. In an in vitro study to investigate release of EGF from the formulations, the release rate was 97.3% after 24 h. In in vivo studies, animals were divided into six groups as follows: silver sulfadiazine [Silverdin cream (SIL)], chitosan gel with and without EGF (EJ, J), EGF solution (ES) and untreated control groups [unburned (S) and untreated (Y) rats] applied groups, respectively. A uniform deep second-degree burn of the backskin was performed with water heated to 94+/-1 degrees C during a 15-s exposure. The EGF formulations were repeatedly applied on the burned areas with a dose of 0.160 microg/cm2 for 14 days (one application per day). Healing of the wounds was evaluated immunohistochemically, histochemically and histologically on the tissue samples. When the results were evaluated immunohistochemically, there were significant increases in cell proliferation observed in the EGF containing gel applied group (p<0.001). The histochemical results showed that the epithelization rate in the EJ group was the highest compared to the ES group results (p<0.001). The histological results indicated and supported these findings. It can be concluded that a better and faster epithelization was observed in the EJ group compared to the other groups.     

创面愈合过程中内源性EGF变化的研究

为探讨创面愈合的机理，本实验采用免疫组织化学方法，对大鼠中厚皮片供皮区创面愈合过程中第４、８、１２和１６天创面内源性表皮生长因子（Ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒ，ＥＧＦ）的变化进行了研究。结果表明，创面愈合过程中内源性ＥＧＦ含量表现有规律性变化，以伤后第８天含量最多，伤后早期和晚期次之，创面愈合后其含量进一步减少。结论：创面愈合过程中，内源性ＥＧＦ的变化促进了创面愈合，是创面愈合的机理之一，结合内源性ＥＧＦ变化，合理外用ＥＧＦ对创面愈合可能会取得促进的效果。     

The combined effect of recombinant human epidermal growth factor and erythropoietin on full‐thickness wound healing in diabetic rat model

Diabetic wound is a chronic wound in which normal process of wound healing is interrupted. Lack of blood supply, infection and lack of functional growth factors are assumed as some of the conditions that lead to non‐healing environment. Epidermal growth factor (EGF) acts primarily to stimulate epithelial cell growth across wound. Erythropoietin (EPO) is a haematopoietic factor, which stimulates the production, differentiation and maturation of erythroid precursor cells. This study hypothesised combining these two factors, non‐healing process of diabetic wound will be compensated and eventually lead to acceleration of wound healing compared with single growth factor treatment. A total of 30 diabetic Sprague–Dawley rats were divided into three treatment groups (single treatment of rh‐EPO or rh‐EGF or combined treatment on a full‐thickness skin wound). To assess the wound healing effects of the components, the wound size and the healing time were measured in each treatment groups. The skin histology was examined by light microscopy and immunohistochemical analysis of proliferating markers was performed. The combined treatment with rh‐EPO and rh‐EGF improved full‐thickness wound significantly (P < 0·05) accelerating 50% healing time with higher expression of Ki‐67 compared with single growth factor‐treated groups. The combined treatment failed to accelerate the total healing time when compared with single growth factor treatments. However, the significant improvement were found in wound size reduction in the combined treatment group on day 4 against single growth factor‐treated groups (P < 0·05). This study demonstrated that the combined treatment of rh‐EPO and rh‐EGF improved the wound healing possibly through a synergistic action of each growth factor. This application provides further insight into combined growth factor therapy on non‐healing diabetic wounds.     

神经肽P物质与烫伤创面愈合关系的实验研究

目的　探讨神经肽P物质(SP)与烫伤创面愈合之间的关系。　方法　(1)制作大鼠不同深度烫伤模型,分别于伤后1、3、7、14d致死,用放射免疫法测定创面SP含量。(2)将大鼠肉芽组织成纤维细胞(GTF)用不同培养液培养,分为空白对照组、SP组及SP SP受体拮抗剂(Spantide)组。体外检测SP及Spantide对GTF增殖活性[以吸光度(A)值表示]及凋亡率的影响。　结果　(1)伤后1d,浅Ⅱ、深Ⅱ、Ⅲ度烫伤创面SP含量分别为(145±78)、(94±48)、(53±27)ng/g,深Ⅱ度创面与其余两者比较,差异有统计学意义(P<0 01).浅Ⅱ度创面伤后3、7dSP含量显著增高;深Ⅱ度创面伤后7、14dSP含量显著增高;Ⅲ度创面伤后SP含量无显著变化。(2)SP增强GTF增殖活性(空白对照组A为0. 21±0. 05,SP组A为0. 36±0 07,P<0. 01)并抑制其凋亡,Spantide可抑制SP对GTF的作用。　结论　SP可促进GTF增殖,创面SP含量与创面损伤程度及愈合能力关系密切。     

Sustained local application of low-dose epidermal growth factor on steroid-inhibited colonic wound healing

Background/purpose

The effects of locally administered low-dose epidermal growth factor in a steroid-inhibited wound healing were investigated in a rat model.

Methods

Long-acting release of epidermal growth factor was enabled using microspheres embedded in gelatin sponge. Study groups consisted of 60 rats with 10 in each: colonic anastomosis only (C), plus pure gelatin sponge (CG), plus epidermal growth factor loaded sponge (CE), colonic anastomosis and steroid (S), plus gelatine sponge (SG), and plus epidermal growth factor-loaded gelatine sponge (SE) groups. Bursting pressure and wound hydroxy-proline content were measured. Bursting sites were recorded. Collagen deposits, inflammation, and foreign body reactions were evaluated.

Results

Bursting pressure and hydroxy-proline contents were found lowest in the S and highest in the CE groups (P < .01). There was almost no difference between C and SE groups. Bursts were encountered in peri-anastomotic normal colon sites in the nonsteroid-treated C, CG, and CE groups. They were noted overwhelmingly at the anastomosis in steroid-inhibited S, SG, and SE groups. Histopathology results showed a standstill at the inflammatory phase of healing in S and SG groups. The best healing was observed in the CE group. Degree of collagen accumulation was well correlated with bursting pressure and hydroxy-proline content data with a negligible foreign body reaction to gelatine sponge.

Conclusions

Continuous local epidermal growth factor administration by microspheres in gelatin increases wound collagen and further enhances healing in colonic anastomoses even with steroid inhibition.     

重组人表皮生长因子促进大鼠皮肤创面愈合的研究

目的观察重组人表皮生长因子(rhEGF)对皮肤创面愈合的作用。方法制作大鼠背部创伤模型,采用自身平行对照,将34只大鼠背部的68个创面分成rhEGF治疗组与盐水对照组,观察大体形态和组织学改变、创面愈合时间和愈合率,测定伤后不同时间创面羟脯氨酸(OHP)含量和Ⅰ型Ⅲ型胶原比例,进行细胞DNA周期分析。结果经rhEGF治疗的创面愈合速度较盐水对照明显加快,2组平均愈合时间为(17.2±1.3)d和(20.5±1.6)d(P<0.01);外用rhEGF使创面肉芽组织生成增多,再上皮化明显,显著增加创面中OHP含量,降低Ⅰ型Ⅲ型胶原比例,加速细胞DNA复制。结论外用rhEGF可缩短创面愈合时间,增加肉芽组织及OHP含量,降低Ⅰ型Ⅲ型胶原比例,加速细胞DNA复制,明显促进皮肤创面的修复。     

表皮生长因子不同用药方法对供皮区治疗的作用

目的　探索外用重组人表皮生长因子治疗供皮区创面的最佳用药方法 ,以指导临床应用。方法　设生理盐水治疗为自身对照 ,选择三种用rhEGF的方法 (每日 1次法 ,每日 3次法 ,每日 1次加保湿法 ) ,进行供皮区创面愈合的比较性研究。结果　和对照组相比 ,rhEGF可有效促进供皮区创面愈合 (P <0 .0 1 )。三种用药方法之间比较 ,差别具有显著性意义 (P <0 .0 5) ,每日 1次加保湿法和每日 3次法均能进一步缩短创面愈合时间。结论　从方便、经济与合理的角度考虑 ,每日 1次加保湿法为临床首选     

藻酸盐敷料与mEGF联合应用对难愈性创面bFGF影响的随机对照试验

目的:探讨联合应用藻酸盐敷料(alginate dressing)与冻干鼠表皮生长因子(mouse epidermal growth fac-tor,mEGF)对难愈性创面碱性成纤维细胞生长因子(basic fibroblast grow thfactor,bFGF)表达的影响,评价其疗效。方法:采用前瞻性、随机、对照设计方法,选择经常规换药抗炎治疗1个月创面仍未愈合的18例患者,年龄18～61岁,平均36.4岁;男12例,女6例;足部11例,小腿3例,手4例。随机分成3组:藻酸盐敷料与mEGF联合治疗组(A组)、mEGF治疗组(B组)、常规治疗组(C组),每组6例。治疗7、14、21、28d后评价其创面愈合指数,7d和14d时行活组织检查常规病理学观察,免疫组织化学SP法评定bFGF表达阳性细胞数目。结果:A、B组创面愈合均明显,A组较B组突出(P<0.05)。病理学检查显示:A组创面修复细胞增殖明显,表皮增厚,上皮化活跃;B组虽也有类似改变,但不如A组显著。免疫组织化学SP染色显示:3组bFGF表达均有上调,但以A组最为显著(P<0.05)。结论:藻酸盐敷料与mEGF联合应用治疗难愈性创面,能协同两者优势,较单用mEGF疗效更佳。     

P物质对肉芽组织成纤维细胞bFGF表达的调控作用及意义

目的　观察感觉神经肽P物质 (substanceP ,SP)对离体培养的肉芽组织成纤维细胞中碱性成纤维细胞生长因子 (basicfibroblastgrowthfactor ,bFGF)表达的特点及调控作用。　方法　采用甲醛注射的方法造成Wistar大鼠局部无菌性炎性反应 ,提取肉芽组织进行成纤维细胞原代培养 ;采用RT PCR方法检测SP对肉芽组织成纤维细胞bFGF基因表达的调控作用 ,观察时间及剂量 效应关系 ;采用Western blot方法检测bFGF蛋白表达情况 ,观察时间及剂量 -效应关系。结果　 10 -7mol/LSP可诱导成纤维细胞bFGFmRNA的表达 ,在作用后 3、6h与对照组比较 ,差异有非常显著性意义 (P <0 .0 1) ;12h后可检测到bFGF蛋白表达明显增强 (P <0 .0 1) ,2 4h达高峰 ,4 8h后逐渐回落。SP在 10 -9～ 10 -5mol/L范围内可显著促进成纤维细胞bFGFmRNA表达 ,在 10 -8～ 10 -5mol/L范围可诱导bFGF蛋白的表达 ,均在 10 -7mol/L剂量点达到峰值 (P <0 .0 1)。　结论　SP可诱导肉芽组织成纤维细胞bFGF基因和蛋白的表达 ,且呈现出一定的时间和剂量特点 ,在SP调控创伤愈合的作用中具有重要意义。     

人绒毛膜促性腺激素对青春期前低促性腺激素性腺发育不良型小阴茎皮肤组织表皮生长因子及其受体的影响

目的 观察人绒毛膜促性腺激素(HCG)对青春期前低促性腺激素性腺发育不良型小阴茎皮肤组织表皮生长因子(EGF)及其受体(EGFR)的影响.方法 10例经临床确诊的青春期前低促性腺激素性腺发育不良型小阴茎患儿予以HCG治疗;10例正常儿童为正常组.分别于治疗前、治疗后3个月进行阴茎长度测量;用酶联免疫吸附试验(ELISA)定量检测阴茎皮肤组织EGF的含量;用免疫组织化学染色(SP法)检测阴茎皮肤组织EGFR的表达.结果所有患儿治疗前阴茎长度(2.44±0.24)cm较正常组(4.29±0.26)cm短(P<0.01);其阴茎皮肤组织EGF含量(43.788±15.375)ng/L较正常组(87.106±14.483)ng/L低(P<0.01);其阴茎皮肤组织EGFR的吸光度(AD)为0.224±0.047,较正常组0.264±0.046差异无统计学意义(P>0.05).经HCG治疗后其阴茎长度(3.97±0.27)cm较治疗前(2.44±0.24)cm明显增长(P<0.01);同时其阴茎皮肤组织EGF的含量(75.694±16.014)ng/L较治疗前(43.788±15.375)ng/L升高(P<0.01);其阴茎皮肤组织EGFR的AD为(0.242±0.054),较治疗前(0.224±0.047)差异无统计学意义(P>0.05).结论 青春期前低促性腺激素性腺发育不良型小阴茎组织内EGF的含量低于正常同龄期儿童;HCG治疗可促进青春期前低促性腺激素性腺发育不良型小阴茎组织EGF的含量升高,从而促进阴茎生长发育.     

The correlation between serum epidermal growth factor/testicular epidermal growth factor receptor and spermatogenesis in rat

<正>Objective: To investigate the correlation between epidermal growth factor (EGF)/testicular epidermal growth factor receptor (EGF-R) and spermatogenesis in rat. Methods: Forty mature male Spraque-Dauley (SD) rats were randomly assigned to four groups, ten rats in each: sham operation group (SOG), sialoadenectomy group(SG), sialoade-nectomy group with injection of EGF (0. 25 μg·kg-1·d-1, SG-EGF Ⅰ) and sialoadenectomy group with injection of EGF (0. 50 μg·kg-1·d-1 , SG-EGF Ⅱ). The rats were routinely feed, and blood and testes were obtained on the 48th day after the operation. Serum EGF concentrations were determined by radioimmunoassay (RIA) , expression of EGF-R in testes was examined by the immunohistochemical method, and the spermatogenesis was pathologically checked. Results: Serum EGF levels in SG-EGFIand SG decreased significantly when compared with those of SOG (P<0. 05 and P< 0. 01, respectively). The testicular function of spermatogenesis showed a moderate to severe impairment in SG. The expression of EGF-R in Leydig cells decreased in SG(P<0. 05). The two dosage groups of EGF replacement had different effects. There were no significant differences of EGF-R expression in testicular germ cells, Sertoli cells and Leydig cells in SOG, SG-EGFⅠand SG-EGFⅡ(P>0. 05). Conclusion: EGF may play an important role in the regulation of spermatogenesis. Serum EGF concentration and high expression of EGF-R in Leydig cells have a positive correlation with spermatogenic function of the testes.     

大鼠血清表皮生长因子和睾丸表皮生长因子受体与精子生成的相关性

目的　探讨血清表皮生长因子 ( EGF)和睾丸组织表皮生长因子受体 ( EGF-R)与大鼠精子生成的关系。　方法　 40只性成熟期雄性 SD大鼠 ,随机分为假手术组( SOG)、去颌下腺组 ( SG)、去颌下腺加腹腔注射 EGF I组 ( SG-EGF I)和 II组 ( SG-EGFII) ,每组 1 0只。SG-EGF I和 SG-EGF II分别腹腔内注射 EGF0 .2 5和 0 .50 μg·kg- 1·d- 1。大鼠常规喂养 48d,断头取血和睾丸。放射免疫法检测血清 EGF水平 ,病理检查睾丸生精功能和免疫组织化学检测睾丸组织 EGF-R的表达。　结果　大鼠血清 EGF水平SG-EGF I组明显下降 ( P<0 .0 5) ,SG组有非常显著下降 ( P<0 .0 1 ) ;睾丸生精功能中、重度障碍 ;间质细胞 EGF-R表达明显减少 ( P<0 .0 5)。补充不同剂量的 EGF对睾丸生精功能有不同影响。 SOG、SG-EGF I和 SG-EGF II大鼠睾丸生精细胞、支持细胞及间质细胞 EGF-R表达无显著性差异 ( P>0 .0 5)。　结论　EGF对精子发生具重要的调控作用 ,血清 EGF水平和睾丸间质细胞 EGF-R高表达与睾丸生精功能呈正相关     

P物质在诱导肉芽组织成纤维细胞增殖中的作用

目的　探讨感觉神经肽P物质 (substanceP ,SP)对离体培养的肉芽组织成纤维细胞的促增殖作用及其对碱性成纤维细胞生长因子 (basicfibroblastgrowthfactor,bFGF)基因表达的调控作用。　方法　采用MTT法测定SP对原代培养的肉芽组织成纤维细胞的促增殖作用 ;采用RT PCR方法检测SP对成纤维细胞bFGF基因表达的调控作用 ,观察时间及剂量 效应关系。　结果　 10 -9～ 10 -5mol/L的SP在体外对原代培养的肉芽组织成纤维细胞均具有明显的促增殖作用 (P <0 0 1) ,且具有明显的剂量依赖性 (r=0 5 94 ,P <0 0 1) ,bFGF抗体能部分抑制这一作用。在作用后 3、6hSP可诱导成纤维细胞bFGFmRNA的表达 ,在 10 -9～ 10 -5mol/L范围内均可以显著促进成纤维细胞bFGFmRNA表达 ,在 10 -7mol/L达到峰值 (P <0 0 1)。　结论　SP对肉芽组织成纤维细胞具有明显的促增殖作用 ,这种作用与其诱导内源性bFGF基因表达有关     

乳腺癌细胞中表皮生长因子对雌激素受体表达的影响及机制

目的研究表皮生长因子（EGF）在雌激素受体（ER）阳性及阴性乳腺癌细胞株中对ER表达的影响及其可能的机制。方法以逆转录-聚合酶链反应（RT—PCR）技术分别研究EGF途径以及抑制该途径的信号传导后，对乳腺癌细胞株中ERcxmRNA的影响。结果在ER阳性乳腺癌细胞株中，EGF能显著抑制ERα mRNA的表达（P〈0．05），而通过抑制表皮生长因子受体（EG-FR）、磷脂酰肌醇3激酶（P13K）阻断EGF信号传导可减弱上述抑制作用（P〈0．05）；在ER阴性乳腺癌细胞株中，ERα mRNA无显著变化。结论EGF能够明显抑制ER阳性乳腺癌细胞株中ER的表达，这种抑制作用可能通过EGFR、蛋白激酶B（PKB，又称AKt）信号传导途径完成；这种作用在ER阴性乳腺癌细胞株中并不明显。     

The effect of various concentrations of human recombinant epidermal growth factor on split-thickness skin wounds

Epidermal growth factor (EGF) is a potent stimulant of epithelialisation. However, topical application of EGF to achieve facilitated re-epithelialisation in partial thickness wounds has been controversial. A total of 10 pigs, each with eight 4 x 4 cm partial thickness wounds, were treated twice a day for 10 days to observe the effect of human recombinant EGF in concentrations of 0.1, 1, 5, 10, 25 ug/g, vehicle only and two controls. The control and the vehicle-only wounds each demonstrated 100% healing time (HT100) of 9.31 +/- 1.34 and 8.5 +/- 1.12 while the wounds treated with EGF ointment with concentrations of 0.1 (HT100 = 6.4 +/- 0.71), 1 (HT100 = 5.2 +/- 0.63), 5 (HT100 = 5.8 +/- 0.85), 10 (HT100 = 7.1 +/- 1.45) and 25 ug/g (HT100 = 7.4 + 0.57) demonstrated significant reduction in time to achieve re-epithelialisation. Among the EGF-treated wounds, the wounds treated with EGF concentrations of 1 and 5 ug/g achieved the fastest re-epithelialisation with evidence of substantial increase in basal keratinocyte activity observed through Ki-67 activity. In conclusion, this article demonstrates the efficacy of human recombinant EGF in facilitating re-epithelialisation of partial thickness wounds with the most efficient healing found in EGF concentrations of 1 and 5 ug/g.     

创面愈合过程中内源性FGF含量变化的研究

为探讨创面愈合的机制，本实验通过免疫组织化学方法，对大鼠断层供皮区创面愈合过程中伤后４天，８天，１２天和１６天创面内源性成纤维细胞生长因子（ＦｉｂｒｏｂｌａｓｔＧｒｏｗｔｈＦａｃｔｏｒ．ＦＧＦ）变化进行了研究。结果表明：创面愈合过程中内源性ＦＧＦ有规律性变化，以伤后８天时相对含量最多，伤后早期和伤后晚期次之，创面愈合后其内源性含量进一步减少。结论：创面愈合过程中，内源性ＦＧＦ的变化促进了创面愈合，是创面愈合的机制之一，结合内源性ＦＧＦ变化，合理外用ＦＧＦ对促进创面愈合可能会取得更好的效果。     

Intralesional administration of epidermal growth factor‐based formulation (Heberprot‐P) in chronic diabetic foot ulcer: treatment up to complete wound closure

Previous studies have shown that an epidermal growth factor‐based formulation (Heberprot‐P) can enhance granulation of high‐grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full‐thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16·3 ± 21·3 cm². Intralesional injections of 75 μg of Heberprot‐P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23·6 ± 3·8 days. Complete wound closure was obtained in 17 (85%) cases in 44·3 ± 8·9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and ardour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot‐P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU.