[生物医药论文精品]茶多酚乳剂促进皮肤溃疡愈合的实验研究

1茶多酚乳剂促进皮肤溃疡愈合的实验研究摘要目的观察茶多酚乳剂促进家兔皮肤溃疡愈合的作用。方法将15只白色家兔均分为5组，每组3只家兔。第1组为基质组（阴性对照），第2组为重组人表皮细胞生长因子组（阳性对照），第3、第4和第5组分别为茶多酚乳剂1、3和6浓度组（小、中、大剂量组）。以涂搽药物后不同时间的各组溃疡面积，溃疡容积和组织病理学检查为指标，观察茶多酚乳剂涂搽对溃疡愈合的影响。结果涂搽茶多酚乳剂3天后，可使溃疡面积和容积缩小速度高于基质对照组。涂搽14天后，组织病理学检查显示6的茶多酚乳剂组（大剂量组）表皮完全覆盖率和50覆盖率高于基质对照组。结论茶多酚乳剂涂搽皮肤溃疡面，可促进溃疡愈合。关键词茶多酚；乳剂；重组人表皮生长因子；皮肤溃疡；动物模型EXPERIMENTALSTUDYOFTHETEAPOLYPHENOLCREAMENHANCINGHEALINGOFSKINULCERINRABBITABSTRACTOBJECTIVETOINVESTIGATETHEEFFECTSOFTEAPOLYPHENOLCREAMTPCENHANCINGHEALINGOFSKINULCERSINRABBITSMETHODS15ALBINORABBITSWEREUSEDINTHISSTUDYFOURSKINULCERSWITHTHESAMEDEPTHINTOHYPODERMAWEREINCISEDONTHEBACKOFEACHRABBITS60ULCERWEREDIVIDEDINTOFIVEGROUPSTHEFIRSTGROUPWERETREATEDWITHCREAMBASE,THESECONDGROUPWERETREATEDWITHRECOMBINANTHUMANEPIDERMALGROWTHFACTORRHEGF,THETHIRDGROUP,THEFOURTHGROUPANDTHEFIFTHGROUPWERETREATEDRESPECTIVELYWITHTHETPCOFSMALL,MODERATEANDLARGEDOSESTHEEFFECTONULCERHEALINGWASASSESSEDBYMEASUREMENTSOFULCERAREA,ULCERVOLUMEANDHISTOPATHALOGICALCHANGESOFEACHGROUPRESULTSATTHE3RDDAYAFTERTPCSMEAR,INTHETPCTREATEDGROUPSANDRHEGFTREATEDGROUP,ULCERAREAANDULCERVOLUMEWERESMALLERSIGNIFICANTLYTHENINTHECREAMBASEGROUPATTHE14THDAYAFTERTPCSMEAR,HISTOPATHOLOGICALEXAMINATIONREVEALEDTHATTHERATEOFALLULCERREEPITHELIALIZATIONANDTHERATEOFMORETHANFIFTYPERCENTULCERREEPITHELIALIZATIONINTHE6TPCGROUPWEREHIGHERTHANTHATINCREAMBASEGROUPCONCLUSIONLOCALAPPLICATIONOFTHETEAPOLYPHENOLCREAMCANPROMOTESKINULCERHEALINGKEYWORDSTEAPOLYPHENOLTPCREAMRECOMBINANTHUMANEPIDERMALGROWTHFACTORRHEGFSKINULCERANIMALMODEL慢性皮肤溃疡（CHRONICSKINULCER,CSU）是临床G17751G5132G16277的G11154病，G5132G16277于G21647G20130病和G12970G4627病G12573G5751G13785。G16825病G5460G5460G1049G8847不愈，因G8504，G12228G1055为G19602G8847性溃疡。G11752G2058G8847G11115CSU的药物G7389重G16213的临床G5224用G1227G1552。G3281G1881G3818对CSUG8847G11115的G11752G12362多G11540G11536于各G12193细胞生长因子，G3926表皮生长因子（G40G42G41）、G11909性G6116G13432G13512细胞生长因子（G69G41G42G41）、G15892小G7507G15905G2282生长因子（G51G39G42G41）、G17728G2282生长因子G163（G55G42G41G16G163）G12573。G1866G3324临床G5224用G7389G980G4462G6940G7536，G9994G13792，G5194不理G5831。G1039G16213G2419因是G11013于G2031面分G8864大量的G15519白G18250，G3926G18341G4658G15519白G18250，分G16311G1114G1272G2487细胞分G8864的G1881G9316性生长因子G6122G13485G1116的G3818G9316性生长因子A1A0A3A4A2。G3281G3818G7422G16277用中药G8847G11115CSU的G6265G17959，G3281G1881G7389用中药G8847G11115CSU的G6265G17959，G7389G980G4462G11115G6940A1A5A7A8A2。G6117G1216G1075G2159G3282G1186天G9994中G14621药中G4559G6226G7044型、高G6940、G1314G8614的G8847G11115CSU的药物。大G17842G5078皮肤病G2319G19510用G14270G15904G11752G2058的G20G3809G7053茶多酚搽剂G8847G11115G21647G20130溃疡，G2474G5483G1114G17751G9397G5859的G11115G6940，G5647G7389G6940率为G28G20G17G23A1A6A2。G1075G7389G6265G17959茶多酚可促进皮肤G16294质G5430G6116细胞G7389G1009分G16022和生长,G1955G4581细胞G1951G1141A1A9A2。临床G990用茶多酚G2058剂G8847G11115重度G2487G14120溃疡G7389显2G14891G11115G6940A1A10A2A13G9994G13792G7422G16277茶多酚G2058剂促进动物皮肤溃疡愈合G11752G12362的G6265G17959。G6117G1216G11752G2058G1114茶多酚乳剂，G5194对G1866动物皮肤溃疡愈合的作用进G15904G4466G20576G11752G12362，以G1427为G1866临床G5224用G6564供药理学G4466G20576依据。材料与方法1材料11实验动物健康白色家兔，体重2G1702G175KG，雌性G200只，雄性5只，G11013大G17842G2319科大学G4466G20576动物中心G6564供（许可证号SCXK（辽）2003G160002）。12药品和试剂茶多酚（TEAPOLYPHENOL）乳剂G11013大G17842G5078皮肤病G2319G19510药剂科G11752G2058；高、中、G1314浓度的乳剂分别是6、3、G20。重组人表皮生长因子RHG40G42G41G11013深圳G5078华生元基因工程发展G7389限公司生产（2000LU/ML）。13主要仪器MA2G230电子天平G990海第二天平仪器厂G2058造；OLYMG51USBX5G13432G13512镜日本OLYMG51US公司G2058造。2方法21分组及皮肤溃疡的制备将G205只家兔均分为5组，每组雌性2只，雄性G20只。G4466G20576前禁食G202H，G4466G20576时用3戊巴比妥钠溶液30MG/KG腹G14120注射G21647醉。按文献A11A12A14G7053法G5194稍作修改，G2058备皮肤溃疡模型。做法G3926下背部剪毛，面积约8CM6CM。用碘酒、酒精消G8614皮肤后，G3324背部脊柱两侧各旁开G20CM处，G11013前至后G2058备G23个皮肤溃疡模型（每测2个）。G2058备时用镊子将皮肤G6564起，用手术剪横向剪下皮肤全层，G5194略作修剪，使肉G11536观察溃疡面积大致相G12573，G2058G6116全层皮肤缺损的溃疡模型，止G15892后备用。手术当日测量各个溃疡的面积和容积，第2日开始G13485药。第G20组3只家兔的G202个溃疡面为药物基质对照组（阴性对照），每次每个溃疡面涂基质0G17G20G。第2组3只家兔的G202个溃疡面为重组人表皮生长因子组（阳性对照），喷涂量为G2000IU/CMA15溃疡面。第3、G23、5组为茶多酚乳剂小、中、大剂量组，每组3只家兔的G202个溃疡面分别涂搽G20、3、6的茶多酚乳剂，每次每个G2031面为0G17G20G。以G990各组G13485药均为G990午8点和下午G23点各G20次，G17842续G20G23天。22检测指标2G172G17G20溃疡面积G1272后即刻及药后3和G20G23天，用G17891G7138G3621G7021G10267覆盖溃疡面，用G12520G2022G1998溃疡G17805G13548，G8851G17805G13548剪下G3621G7021G10267，G13634分度G1552为0G17G20MG的电子天平G12228重，G5194按G20CMA15G3621G7021G10267的重量，将G1866重量G6454G12651G6116面积。2G172G172溃疡容积G1272后即刻、药后3天，用G20MLG7092G14752的注射器向溃疡G14120G1881G9416G1849G9793G14752生理G11428G8712，至液面G994皮肤G17805G13548相平为止，G16772G5417G9416G1849量，G1866为溃疡容积。2G172G173组织病理学检查药后G20G23天，G1889次用3戊巴比妥钠溶液腹G14120注射，使家兔G21647醉。G2474溃疡面组织，G13634G200G12131G4584G20544G7531溶液中G3278G4462，G5132G16280G11719G15605G2265G3487，G2058G10267，G14499G7420G13044G1246G13430（G43G40）G7591色，G1821镜下观察，G5194G6305照。23统计学方法用SG51SSG20G20G175G17731G1226进G15904G13491G16757学处理。G16757量G17176G7021以G91G102S表示G18331用G2345因G13044G7053G5058分G7524，组间两两比G17751G18331用LSG39法；G16757G6980G17176G7021G18331用G12221和检G20576。G51G310G1705为G7389显G14891性G5058G5334。结果11TP乳剂对溃疡面积和容积的影响G2058作皮肤溃疡模型后，即刻对G1866面积和容积进G15904测量G5194进G15904G13491G16757学处理，G134793G7536G16277表G20。表G20G17即刻的皮肤溃疡模型面积和容积组别溃疡个G6980/N溃疡面积/G897A16溃疡容积/ML基质对照组12356G1020G17G233057G1020G170G26RHEGF12318G1020G17G23G23A17052G1020G17G2001TP3TP6TP121212399G1020G1730A17A173G1788G1020G1733A173G17G26G23G1020G1730061G1020G17030G176G23G1020G170G23A17A170G1762G1020G1703A17G91G102SG39，G994基质组比G17751，P错误未找到引用源。005,P错误未找到引用源。001表1G13479G7536G6564示G2058作的溃疡面积和容积G994基质组比G17751，G3324G7588G1135组G7389G13491G16757学的显G14891性G5058G5334。G6937药物促进溃疡愈合的G6940G7536以面积G6122容积缩小的G11346分率（）表示。按G3926下公G5347G16757G12651面积G6122容积缩小的G11346分率（）（药后的面积G6122容积G713即刻的面积G6122容积/即刻面积G6122容积）G854100TP乳剂促进溃疡面积缩小的G11346分率G3926表2G6164示。表2TP乳剂促进皮肤溃疡面积缩小的G11346分率（）基质组溃疡个G6980/N药后天G6980/天314基质对照组12562G1023G17G2328106G102G203G1766RHEGF121199G1026G1758A17G28G26G178G26G1022G17G2601TP12G205G1725G102G23G17G236A17A179595G1025G17253TP122G28G17G283G102G20G20G17G23G28A17A17A17G28G26G17G28G28G1022G17636TP1228G17G28G20G102G200G176G23A17A17A17G288G17G233G1023G1723XG102S,G994基质组比G17751，P错误未找到引用源。005,P错误未找到引用源。001,P错误未找到引用源。0001表2G13479G7536表G7138TP乳剂涂搽G3324家兔皮肤溃疡表面，G3324用药后第3天，G2588剂量依G17194性G3332促进皮肤溃疡愈合。G13792G3324药后第14天，G11013于基质组G1075G14270G9994愈合，G6937各组间G7092G13491G16757学显G14891G5058G5334性。TP乳剂促进药后3天皮肤溃疡容积缩小的G11346分率G3926表3G6164示。表3TP乳剂促进药后3天皮肤溃疡容积缩小的G11346分率（）4组别溃疡个G6980N缩小基质对照组121241G1021381RHEGF组122357G10216671TP组123351G10217683TP组123913G1029696TP组122908G102893XG102S,G994基质组比G17751，PG19181G16835G701G7422G6226G2052G5353用G9316。005,PG19181G16835G701G7422G6226G2052G5353用G9316。001,PG19181G16835G701G7422G6226G2052G5353用G9316。0001G13479G7536表G7138TP乳剂G13485药3天可使皮肤溃疡容积缩小，G994基质组比G17751，G7389G13491G16757学显G14891G5058G5334。G6564示TP乳剂对皮肤溃疡愈合G7389促进作用。药后第14天，G11013于各组溃疡G7389的基本愈合，即使G7389的G7422愈合，G8543G11053的溃疡容积G1075G5468小，不G14033进G15904测量容积的G4466G20576，G6937G7422测G4462药后第14天的溃疡容积。12TP乳剂对溃疡组织病理学的影响组织病理学检查的分G13435G13479G7536G16277表4。表4TP乳剂对皮肤溃疡组织病理学影响的分G13435组别组织病理学改G2476G12221和检G20576A18A19A20A21A22A23A24A25A26A23A27A28A2950A24A25A26A23A27A28A3050A31A32A33A34A35A36A37A38A39A40A41/NA37A38A39A40A41/NA37A38A39A40A41/NA42A43A440012RHEGF组223PG310051TP组008PG4560053TP组008PG4560056TP组336PG31005表4G13479G7536表G71386TP组表皮完全覆盖的溃疡个G6980和表皮覆盖面积大于50的溃疡个G6980高于基质组（PG728005）。组织病理的照G10267G13479G7536显示基质对照组G990皮G2282程度不G1351（G32821）,G13792涂搽6TP的乳剂14天后，表皮生长G14403G3921，G7389的溃疡面完全表皮G2282（G32822）,G13792喷涂RHEGF溶液14天后，G1075显示表皮生长G14403G3921，G1075G7389的溃疡面完全表皮G2282（G32823）。5G32821基质涂搽14天,对皮肤溃疡组织病理学的影响HEG7591色,40显示G990皮G2282程度不G1351G328226的TP乳剂涂搽14天,对皮肤溃疡组织病理学的影响HEG7591色,40显示溃疡面完全表皮G22826G32823RHEGF溶液喷涂14天,对皮肤溃疡组织病理学的影响HEG7591色,40显示溃疡面完全表皮G2282讨论本G11752G12362以家兔皮肤溃疡面积和容积以及G1821镜下组织病理学G2476G2282为指标,观察茶多酚乳剂涂搽对皮肤溃疡愈合的影响。G13479G7536证G7138，涂搽药后3天,茶多酚乳剂大、中、小剂量组对溃疡面积和容积缩小均G7389促进作用,G994基质组比G17751,均G7389G13491G16757学显G14891G5058G5334。组织病理学检查G1075证G7138大剂量茶多酚乳剂G7389G14403G3921的促进溃疡面表皮生长的作用,G994基质组比G17751,G7389G13491G16757学显G14891G5058G5334。G4447G12180G12074G12573G11752G12362证G7138茶多酚的G7389G6940G6116分G1055G980的表G8821食子G1811茶G13044G8821食子G18252G18243,对G3533G1871的人皮肤G13432G13512细胞,可G1955G4581UVBG17764射G5353起的MDA的G8797积,G3698G2164G6251G8699G2282G18250G8975性,G5194可G6245G2058UVBG16837G4560的基质G18341G4658G15519白G182501MMP1MRNA表G17810,G1955G4581G14026G2419G15519白的G19489G16311。G1186G13792,对UVBG17764射损G1272的体G3818G3533G1871的G6116G13432G13512细胞起G2052G1457G6264作用10。G18082G7702G10630G12573G11752G12362证G7138茶多酚对HEPG2细胞损G1272G7389G1457G6264作用,可G6564高损G1272后的HEPG2细胞生G4396率11。G4499G17867G14750G12573G1075G6265G17959茶多酚是天G9994G5390G6251G8699G2282剂,可以G7389G6940G3332G9177G19512皮肤中产生的多G1325G8699G14270G11013基,G6245G2058皮肤中的致G9826G14752和致G9826因子,对皮肤G9826G11163G7389G5468G3921的G8847G11115作用12。G20771朝G14403G12573G6265G17959酚羟基G994G14270G11013基反G5224可G5430G6116稳G4462的半酮G5347G14270G11013基G13479构,G1186G13792终止G14270G11013基链G5347反G5224。这样可以G1955轻G14270G11013基对细胞的DNA损G127213；G13792茶多酚类G7389酚羟基。以G990作用可G14033G994茶多酚促进皮肤溃疡愈合G7389关。确切的作用机G2058尚需进G980步G11752G12362确G4462。参考文献1WENERS,GROSERREGULATIONOFWOUNDHEALINGBYFACTORSANDCYTOKINESJPHYSIOLREV,2003,8338358702STAMENKOVICIEXTRACELLULARMATRIXREMODELINGTHEROLEOFMATRIXMATALLOPROTEINASESJJPATHOL,200320044484643孙晋G6116G13432G13512细胞生长因子G1