表皮细胞生长因子和受体在胎儿肠道细胞中的表达特征及其意义

目的研究表皮细胞生长因子(EGF)及其受体(EGFR)在胎儿和成人小肠组织中的表达特征以及可能的生物学意义.方法21例被测标本中包括不同胎龄的胎儿小肠组织19例和成人小肠组织2例.用免疫组化方法和病理技术确定这两种蛋白在胎儿和成人小肠组织中的定们和表达量的变化规律.结果EGF及其受体在不胎龄的胎儿和成人小肠组织中都有阳性表达.随着胎儿生长发育,小肠组织中EGF和EGFR的蛋白含量逐渐啬,这一变化趋势一直保持到成人皮肤组织中,其中EGF蛋白主要存在于小肠粘膜上能上能下细胞、粘腊下层的血管内皮细胞内和浆膜上皮细胞的胞浆和胞外基质中,EGFR则分布于这些细胞的细胞膜上.结论EGF的生长发育、结构和功能的维持以及损伤后的修复.     

膀胱移行细胞癌表皮生长因子及其受体表达和意义

目的 探讨表皮生长因子(EGF)、EGF受体(EGFR)在膀胱移行细胞癌(BTCC)中的表达及意义。方法 用免疫组化ABC法对56例BTCC标本和20例癌旁组织EGF、EGFR进行研究。结果 20例癌旁正常膀胱组织中EGF，EGFR几乎不表达；56例ETCC标本中EGF，EGFR表达明显，与正常组比较有显著性差异(P＜0．01)，不同分期和分级BTCC中的阳性表达率均存在显著性差异(P＜0．05)。结论 EGF，EGFR的检测可以作为判断BTCC预后的一个指标。     

PCNA,EGF,EGFR在正常口腔粘膜中的表达及其意义

目的:观察增殖细胞核抗原(PCNA)、表皮细胞生长因子(EGF)及表皮细胞生长因子受体(EGFR)在正常口腔粘膜组织(NM)中表达及分布情况.方法:用免疫组化技术检测PCNA、EGF、EGFR在NM中的表达.结果:PCNA在NM的阳性表达主要出现在基底细胞层细胞的细胞核;EGF的蛋白颗粒在NM中主要分布于基底层细胞和棘层细胞中,阳性表达出现在胞浆中;在NM中EGFR表达主要位于基底细胞层细胞的细胞膜.结论:口腔粘膜上皮的基底细胞层细胞具有分裂增殖能力,EGF、EGFR的表达与口腔粘膜上皮分裂增殖密切相关.     

EGF对TPN大鼠肠粘膜细胞EGFR表达的影响

利用大鼠全肠外营养(TPN)模型,探讨表皮生长因子(EGF)对TPN支持后肠粘膜细胞表皮生长因子受体(EGFR)表达的影响。方法:48只SD大鼠随机分为对照组、常规TPN组及TPN-EGF组。实验持续14天,采用免疫组化结合计算机图象分析的方法,分别测定颌下腺内EGF含量以及小肠粘膜细胞中EGF和EGPR含量。结果:TPN及TPN-EGF组大鼠颌下腺内EGF含量均明显下降(P<0.01);TPN组小肠粘膜细胞中EGF、和EGFR含量显著下降(P<0.01),而TPN-EGF组则未减少(P<0.05)。结论:内源性EGF分泌减少是TPN肠粘膜屏障损伤的重要原因之一;EGF具有促进肠粘膜细胞EGFR表达的作用。     

TGFα和EGF对前列腺癌细胞系EGFR表达的调控作用

目的：探讨转化生长因子（TGF）α和表皮生长因子（EGF）对前列腺癌细胞系中表皮生长子受体（EGFR）表达的调控作用。方法：采用RT－PCR和Western印迹法分别对TGFα和EGF刺激前列腺癌细胞系LNCaP、PC3、ARCaP后EGFR mRNA表达及其蛋白水平进行定量分析。结果：EGF引起前列腺癌细胞系LNCaP、PC3、ARCaP的EGFR mRNA升高2－5倍,TGFα引起各细胞系EGFR mRNA升高2－10倍。TGFα使各细胞系EGFR不同程度升高;EGF处理的LNCaP EGFR蛋白水平略升高,PC3、ARCaP EGFR蛋白水平降低。结论：TGF／EGF-EGFR通路在前列腺癌发生发展中起重要作用;非依赖型前列腺癌中TGFα－EGFR自分泌环的作用可能强于EGF－EGFR自分泌环。     

胎儿、成人正常皮肤EGFR与FGFR-2表达的研究

目的：观察胎儿与成人正常皮肤中的表皮细胞因子受体（EGFR）与成纤维细胞生长因子受体（FGFR）在细胞膜上表达的差异，探讨胎儿无瘢痕形成的分子机制。方法：对妇产科意外流产的不同妊娠期胎儿和整形外科手术过程中作为供皮区的成人正常皮肤标本，应用免疫组织化学技术观察EGFR与FGFR－2的变化。结果：妊娠台儿的皮肤内EGFR和FGFR－2染色阳性的表皮细胞较多，贯穿于全层上皮，而真皮中成纤维细胞呈阳性标记的极少，随胎龄的增加，两受体的表达增加，成年人正常皮肤中EGFR多集中在表皮细胞的基底层，两种生长因子受体抗体阳性染色的细胞明显多于胎儿皮肤，结论：胎儿和成年人的皮肤中，EGFR染色与FGFR－2表达的差异，可能是造成胎儿无瘢痕愈合的重要因素之一。     

胎儿和出生后机体皮肤内表皮生长因子和两种原癌基因表达变化及其与胎儿无瘢愈合的关系

胎儿皮肤创面愈合后一般不形成瘢痕,而成人创面愈合常有瘢修复,这一变化的机制目前尚不清楚.在研究中人们发现胎儿无瘢痕愈合不受胎儿所处的无菌、湿润和低氧环境的影响,而可能与伤口处的细胞因子浓度变化密切相关.表皮生长因子(epidermal growth factor,EGF)作为主要的修复生长因子,对创面愈合的多个环节都产生作用.EGFR是一种跨膜酪氨酸激酶受体,与EGF特异性结合后,通过MAPK信号通路,上调c-fos和c-myc等转录因子的基因表达后,诱导细胞核内特异性基因转录,刺激组织修复细胞增殖,趋化炎性细胞,表皮细胞和成纤维细胞向伤口聚集,加速创面愈合.目前,关于EGF,EGFR及其下游信号分子在人不同发育阶段的皮肤组织中的基因表达变化特征还缺乏研究,对这一规律的揭示,将有利于深入了解EGF调节创面愈合的机制和早期妊娠胎儿皮肤创面无瘢痕愈合的部分奥秘.用病理学技术检测不同发育阶段皮肤的结构特征后,提取18例不同胎龄(13～32周)的胎儿皮肤和6例出生后机体皮肤组织的总RNA,分离mRNA,用R-PCR方法检测这4种基因在不同组织中的表达变化规律.结果显示,在早期妊娠胎儿的皮肤中,EGF,EGFR,c-fos和c-myc基因表达较弱,随着胎儿的生长和发育,皮肤组织内这三种基因表达逐渐增强,在出生后机体的皮肤组织中,EGF,EGFR,c-fos和c-myc基因表达进一步升高,基因表达量分别为晚期妊娠胎儿皮肤的1.24倍,1.11倍,1.28倍和1.63倍.EGF、EGFR及其下游信号分子c-fos和c-myc基因在不同发育阶段的人皮肤组织内都有表达,显示EGF与其受体结合后引起的信号通路可能对皮肤的发生、结构功能的维持以及伤后修复十分重要.这4种基因在早期妊娠胎儿皮肤中低表达可能与胎儿皮肤创面无瘢痕修复密切相关.     

前列腺组织中EGF、bFGF的表达

目的：研究EGF、bFGF在前列腺组织中的表达。方法：应用mRNA斑点杂交、原位杂交、免疫组织化学及原位杂交与免疫组织化学双染法检测6例正常前列腺（NP）、27例良性前列腺增生症（BPH）前列腺组织中EGF及bFGF的表达。结果：BPH前列腺组织和NP组织中无均无EGF mRNA表达,EGF蛋白表达呈弱阳性,两组间差异无显著性意义（P＞0.05）;NP组织上皮细胞有较多bFGF mRNA表达,但无bFGF翻译,基底基质细胞有少量mRNA及蛋白表达,二者表达水平基本一致;BPH前列腺组织上皮细胞无bFGF mRNA表达,但局灶性增殖上皮细胞细胞膜上有bFGF,基底基质细胞有大量bFGF mRNA转录及蛋白质翻译,以局灶性增殖区最为明显。结论：NP及BPH的前列腺组织中无EGF分泌细胞;bFGF在前列腺基底基质细胞过度表达,以自分泌、旁分泌方式促进了基质和上皮的非均一性增殖。     

表皮生长因子及其受体对雄性生殖系统的影响

表皮生长因子 (EGF)是首先从小鼠颌下腺分离出来的含 5 3个氨基酸残基的单链多肽 ,通过与其受体(EGFR)相结合发挥多种生物学效应。近年来发现 ,在人类和其他动物的雄性生殖系统有EGF与EGFR表达 ,对雄性生殖器官的发育、维持及变异起着重要的作用 ,同时 ,对雄性激素的分泌和精子发生也有很大的影响。EGFR在睾丸的支持细胞和间质细胞上均有表达 ,可影响睾酮的分泌 ;能维持正常前列腺组织的生长发育 ,刺激前列腺增生组织和前列腺癌组织的生长和分化 ;EGF参与精子发生 ,其作用点主要在减数分裂过程 ;可影响性分化 ,在雄激素诱导下使胚胎向雄性方向发育。     

表皮细胞生长因子和碱性成纤维细胞生长因子在不同发育阶段大鼠皮肤表达特征的比较性研究

目的 研究表皮细胞生长因子（EGF）和碱性成纤维细胞生长因子（bFGF)在胚胎、新生及成年三个不同发育阶段大鼠皮肤的表达特征及其可能的生物学意义。方法 取胚胎、新生和成年大鼠皮肤,经4%多聚甲醛固定、包埋与切片后,用SP免疫组织化学法研究EGF和bFGF的定位与表达特征。结果 EGF的阳性表达可见于胚胎、新生及成年三个发育阶段大鼠皮肤,主要位于表皮棘细胞,真皮成纤维细胞、毛囊上皮细胞和血管内皮细胞胞浆,bFGF在新生和成年大鼠表皮及真皮呈强阳性表达,但在胎鼠皮肤则为弱阳性乃至阴性,结论 EGF在不同发育阶段大鼠皮肤呈强阳性表达,表明其对上皮的发生、表型维持以及损伤后的修复十分重要。而大鼠胚胎皮肤bFGF低表达或缺乏的结果表明它可能是动物胚胎创伤后无瘢痕愈合的原因之一。     

The expression characteristics and biological significance of bFGF, EGF,TGF-β isoforms and their receptors in skins from fetus and adult

To observe the localization and expression characteristics of alpha-smooth muscle actin (AS-MA), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), transforming growth factor-β(TGF-β) isoforms, and their receptors in fetal and adult skins in order to explore their potential biological significance.Methods: The expression and the distribution of ASMA, bFGF, EGF, TGF-βisoforms, and their receptors were detected with immunohistochemistry and histopathology methods in 36 skin specimens. Among them, 30 specimens belonged to fetuses at different developmental stages and 6 were from adults. Results:Positive immunohistochemical signals of ASMA, bFGF, EGF, and TGF-βisoforms and their receptors could be found in fetal and postnatal skins.These factors were mainly distributed in the cytoplasm and extracellular matrix of epidermal cells, endothelial cells,hair follicle epithelial cells and some fibroblasts. Receptors of these factors were mostly located in the cellular membrane of the above mentioned cells, while protein particles of ASMA could be observed in myofibroblasts and sweat gland cells. Along with ascent in gestational age, the positive cellular rates of bFGF, EGF, TGF-βisoforms, their receptors, and ASMA in skin were elevated progressively. In skins specimens obtained from fetuses of late-trimester (29-31 week gestation) and adult, the positive rates of these proteins were significantly raised in comparison with skin of fetuses of early-trimester. Conclusion: The endogenous bFGF, EGF, three TGF-βisoforms and their receptors might be involved in the development of the skin in embryonic stage and in the cutaneous structure and function,and also wound healing in adult stage. The relative lack of these factors and their receptors might be one reason why the wound of fetus heal by regeneration rather than by scarring.     

不同剂量己烯雌酚对新生小鼠睾丸表皮生长因子及受体的影响

目的 观察不同剂量己烯雌酚(DES)对新生小鼠睾丸组织中表皮生长因子(EGF)及其受体(EGFR)的影响,探讨DES对睾丸发育影响的机制.方法 建立小鼠DES模型.将72只怀孕的雌性昆明小鼠随机分成3组:正常组、对照组及实验组1～4(DES 10、25、50、100 μg/kg).采用免疫组织化学方法检测各组新生小鼠睾丸组织中EGF、EGFR的表达.结果 EGF和EGFR主要表达在新生小鼠睾丸的间质细胞.实验组1～4中EGF阳性细胞的累积吸光度值(IA)分别为75.43±1. 42、52.22±5.67、13.75±3.14、6.38±3.20,显著低于正常组及对照组中阳性细胞的IA值433.88±11.64、23.44±4.70;实验组EGFR阳性细胞的IA值分别为198.16±34.35、138.00±12.04、46.03±6.74、27.22±5.52,显著低于正常组及对照组中阳性细胞的IA值804.74±22.52、800.03±21.96.两者在正常、不同剂量DES实验组的两两比较差异有统计学意义(P＜0.05).随DES剂量增加,EGF和EGFR表达减弱,各组间差异有统计学意义(P＜0.05).EGF与EGFR呈强正线性相关(r=0.750,P＜0.01).结论 不同剂量DES对新生小鼠睾丸组织中EGF和EGFR表达强度均有影响,可能是影响睾丸发育机制之一.

Abstract：

Objective To investigate the effects of prenatal exposure to diethylstilbestrol (DES)with different dosages on epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) in offspring mice testis, and the possible mechanism. Methods DES model was induced in mice by DES.Female Kungmiag mice were randomly divided into normal group, control group and experimental groups 1-4 ( DES 10, 25, 50, 100 μg/kg). Immunohistochemistry was applied to detect the expression of EGF and EGFR in the testicular tissue in each group. Results EGF and EGFR were expressed mainly in sffspring mice testis Leydig cells. The cumulative absorbance ( IA ) values of EGF positive cells in experimental groups 1-4 were 75. 43 ± 1.42, 52. 22 ± 5.67, 13.75 ± 3. 14, and 6. 38 ± 3.20 respectively, which were significantly lower than in normal and control groups (433.88 ± 11.64,423.44 ±4. 70 respectively).The IA values of EGFR positive cells in experimental groups 1-4 were 198. 16 ± 34. 35, 138.00 ± 12.04,46.03 ± 6. 74, 27.22 ± 5.52 respectively, which were significantly lower than in normal and control groups (804. 74 ± 22. 52,800. 03 ± 21.96 respectively). The expression levels of EGF and EGFR could be detected in each subgroup and statistically significant differences existed in the expression of EGF and EGFR between any two groups ( P ＜ 0. 05 ). With the increase of DES dosage, the expression of EGF and EGFR was decreased, with the difference being significant amond the groups ( P ＜ 0. 05 ). Conclusion DES can influence the expression of EGF and EGFR in mice testis, which might be one of possible mechanisms effecting the development of testis.     

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.     

汉防己甲素对先天性膈疝大鼠模型胎仔肺内表皮生长因子及其受体的影响和意义

目的 探讨中药成分汉防己甲素（tetrandrine,TET）对大鼠先天性膈疝（congenital diaphragmatic hernia,CDH）模型胎仔肺内表皮生长因子（epidermal growth factor,EGF）及其受体（epidermal growth factor receptor,EGFR）的影响和意义。方法 实验组20只雌性SD大鼠于孕9．5d灌胃给予除草醚115mg／只;对照组4只灌胃给等量食用油。孕18．5d,实验组根据给药不同随机分为生理盐水组（normal solution group,NS组）、地塞米松组（dexamethasone group,Dex组）、汉防己甲素组（tetrandringe group,TET组）、地塞米松＋汉防己甲素组（D＋T组）,每组5只。孕21．5d对所有孕鼠行刮宫产,取出胎鼠两侧肺组织行大体观察、HE染色、EGF、EGFR免疫组织化学染色和图像分析。结果 正常对照组共产胎仔36只,无隔疝形成。实验组共产胎仔137只,CDH形成64只,致畸率46．7％。在Dex组、TET组和T＋D组,肺组织处于原始肺泡期或进一步成熟。EGF在NS组、Dex组、TET组、D＋T组及对照组的表达量依次递减（P〈0．05）,而EGFR在NS组、Dex组、TET组、D＋T组和对照组的表达量依次递增（P〈0．05）。结论 TET可使CDH胎鼠肺内EGF表达高峰提前,使EGFR表达上调,TET和Dex联合作用对促进EGF表达高峰提前及EGFR表达上调具有明显的协同效应。TET可以通过调节EGF及EGFR在肺内的表达而实现其促进肺组织细胞发育分化和改善肺血管构型的效应。     

Effect of substance P released from peripheral nerve ending on endogenous expression of epidermal growth factor and its receptor in wound healing

Objective: To explore the relationship between substance P (SP) released from peripheral nerve endings and the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) during wound bealing. Methods: Fifty Wistar rats were randomly divided into 2 groups, injury group and capsaicin group. In the injury group, a full-thickness skin wound on the back of the rat was taken. The wound edge and granulation tissues were taken on the 1st, 3rd, 6th, 9th, 12th days after injury, respectively. In the capsaicin group, capsaicin was injected subcutaneously on the back of the rats to destroy the sensory nerve to prevent the secretion of SP, then a wound and sample was made in the same way.Immunohistochemistry and in situ hybridization were employed to detect the expression of SP, EGF/EGFR, and EGF mRNA/EGFR mRNA in the granulation tissues.Results: In the injury group,immunohistochemical stain of SP and EGF/EGFR was located on the hair follicles and sebaceous glands at the 1st day. And the stain of SP was obvious at the 3rd day in the granulation tissues, then decreased gradually. EGF/EGFR was at low level at the 3rd day, then increased gradually and reached the peak at the 9th day, then declined. In the capsaicin group, the stain of SP and EGF/EGFR was faint and without obvious change during the wound healing process. The tendency of the EGF mRNA/EGFR mRNA expression was similar to that of EGF/EGFR. Conclusions: During wound healing, SP may promote the healing process by affecting the expression of EGF/EGFR in the erunuation tissues.