表皮生长因子对多器官功能障碍小鼠的作用
표피생장인자대다기관공능장애소서적작용
The role of epidermal growth factor in multiple organ dysfunction of mice
  • 万方数据
    中华急诊医学杂志 중화급진의학잡지
    CHINESE JOURNAL OF EMERGENCY MEDICINE
    2012年 5期 497-502 ,共6页

    徐南平%汪倩%邹音%杨文萍%肖乔梅

    서남평%왕천%추음%양문평%초교매

    重组人表皮生长因子%硫代乙酰胺%多脏器功能障碍综合征%腹腔注射%皮下注射%病死率 重組人錶皮生長因子%硫代乙酰胺%多髒器功能障礙綜閤徵%腹腔註射%皮下註射%病死率
    중조인표피생장인자%류대을선알%다장기공능장애종합정%복강주사%피하주사%병사솔
    Recombinant human epidermal growth factor%Thioacetamide%Multiple organ dysfunction syndrome%Intraperitoneal injection%Subcutaneous injection%Mortality
    目的 研究重组人表皮生长因子(recombinant human epidermal growth factor,rhEGF)对多脏器功能障碍综合征小鼠预后的影响.方法 江西省人民医院动物实验室清洁级雄性昆明种小鼠120只,SPF级,随机(随机数字法)分为生理盐水(normal saline,NS)空白对照组15只、MODS模型对照组15只,采用ME Caballero方法用硫代乙酰胺(thioacetamide,TAA) 2000 mg/kg单次腹腔注射建立单相速发小鼠多脏器功能障碍综合征模型.rhEGF MODS治疗组90只,其中随机(随机数字法)分为两种给药方式:腹腔注射组45只,皮下注射组45只；每组随机分为3个剂量组:10 μg/kg,30 μg/kg和50 μg/kg,每个剂量组15只.观察各组小鼠24 h内呼吸、体质量、饮食等一般情况的变化.24h后,计算各组病死率；颈椎脱臼处死动物后立即收集肝脏、肾脏、心脏、脑、肺、脾脏、胰腺、肠、胃,行苏木素-伊红染色光镜下观察组织学变化.实验数据以均数±标准差((x-)±s)表示,体质量自身变化比较采用t检验,不同给药方式及不同剂量的rhECF给药对MODS小鼠体质量变化影响采用Dunnett法分析；不同给药方式对MODS小鼠病死率的比较采用Fisher精确概率法,以P＜0.05为差异具有统计学意义.结果 rhEGF皮下给药组与MODS模型对照组的病死率比较差异无统计学意义(P＞0.05),但hrEGF MODS腹腔给药组病死率明显低于MODS模型对照组病死率73.3％(P＜0.01),其中腹腔给药50 μg/kg和30 μg/kg剂量组的病死率(6.7％、20.0％)较MODS模型对照组降低(P =0.000,0.009)；而且腹腔给药50 μg/kg的病死率(6.7％)比10 μg/kg更低(P=0.014).同时,rhEGF MODS (50 μg/kg)腹腔给药组的病死率(6.7％)较皮下给药组的病死率(40.0％)降低更明显(P=0.031).在组织病理学上rhEGFMODS治疗组能改善MODS小鼠肝肺组织的损伤,随rhEGF腹腔给药剂量增加,肝淤血程度减轻,肝细胞凋亡减少,肝细胞浊肿和空泡变减少.同时随rhEGF MODS治疗组给药剂量增加肺间质充血减轻,炎细胞减少,偶见凋亡小体,支气管柱状纤毛上皮较少脱落.结论 rhEGF对TAA诱导的MODS小鼠模型的肝肺等脏器的组织损伤有修复作用,且腹腔注射较皮下注射能更有效地降低MODS小鼠的24 h病死率.
    목적 연구중조인표피생장인자(recombinant human epidermal growth factor,rhEGF)대다장기공능장애종합정소서예후적영향.방법 강서성인민의원동물실험실청길급웅성곤명충소서120지,SPF급,수궤(수궤수자법)분위생리염수(normal saline,NS)공백대조조15지、MODS모형대조조15지,채용ME Caballero방법용류대을선알(thioacetamide,TAA) 2000 mg/kg단차복강주사건립단상속발소서다장기공능장애종합정모형.rhEGF MODS치료조90지,기중수궤(수궤수자법)분위량충급약방식:복강주사조45지,피하주사조45지；매조수궤분위3개제량조:10 μg/kg,30 μg/kg화50 μg/kg,매개제량조15지.관찰각조소서24 h내호흡、체질량、음식등일반정황적변화.24h후,계산각조병사솔；경추탈구처사동물후립즉수집간장、신장、심장、뇌、폐、비장、이선、장、위,행소목소-이홍염색광경하관찰조직학변화.실험수거이균수±표준차((x-)±s)표시,체질량자신변화비교채용t검험,불동급약방식급불동제량적rhECF급약대MODS소서체질량변화영향채용Dunnett법분석；불동급약방식대MODS소서병사솔적비교채용Fisher정학개솔법,이P＜0.05위차이구유통계학의의.결과 rhEGF피하급약조여MODS모형대조조적병사솔비교차이무통계학의의(P＞0.05),단hrEGF MODS복강급약조병사솔명현저우MODS모형대조조병사솔73.3％(P＜0.01),기중복강급약50 μg/kg화30 μg/kg제량조적병사솔(6.7％、20.0％)교MODS모형대조조강저(P =0.000,0.009)；이차복강급약50 μg/kg적병사솔(6.7％)비10 μg/kg경저(P=0.014).동시,rhEGF MODS (50 μg/kg)복강급약조적병사솔(6.7％)교피하급약조적병사솔(40.0％)강저경명현(P=0.031).재조직병이학상rhEGFMODS치료조능개선MODS소서간폐조직적손상,수rhEGF복강급약제량증가,간어혈정도감경,간세포조망감소,간세포탁종화공포변감소.동시수rhEGF MODS치료조급약제량증가폐간질충혈감경,염세포감소,우견조망소체,지기관주상섬모상피교소탈락.결론 rhEGF대TAA유도적MODS소서모형적간폐등장기적조직손상유수복작용,차복강주사교피하주사능경유효지강저MODS소서적24 h병사솔.
    Objective To study the role of recombinant human epidermal growth factor (rhEGF) in the prognosis of multiple organ dysfunction syndrome (MODS) in mice. Methods One hundred and twenty clean male Kunming mice were randomly ( random number) divided into normal saline control group (n =15),MODS model control group (n =15) and MODS + rhEGF treatment group (n =90).The MODS models were made by using Caballero ME method with thioacetamide (TAA) 2000 mg/kg injected intraperitoneally to establish monophasic rapid onset pattern of MODS model in mice.MODS + rhEGF treatment group was further randomly divided into two subgroups,namely intraperitoneal injection group (n =45 ) and subcutaneous injection group (n =45 ).Each subgroup was divided again into three small subgroups (n =15) as per different doses of rhEGF used,namely 10 μg/kg,30 μg/kg and 50 μg/kg.Within 24 hours after modeling,the respiration,body weight,food eaten and general physical changes were observed.Mortality was calculated 24 hours after modeling.After the animals sacrificed,the tissues of viscus including liver,kidney,heart,brain,lung,spleen,pancreas,intestine and stomach were collected immediately.The histological changes of visceral tissues were studied by using hematoxylin -eosin staining under the light microscope.All the experimental data were presented in,and body weight changes were compared using t-test,and after different routes of administration with different doses of rhEGF used in MODS,the mice body weight changes were analysed by using the Dunnett method,and the mortalities of mice were compared by using Fisher exact test,and P ＜ 0.05 was considered statistically significant difference. Results There was no significant difference in mortality betweeu mice in rhEGF subcutaneous administration group and MODS model control group (P ＞ 0.05 ),but the total mortality of hrEGF MODS intraperitoneal administration group (6.7％ in dose of 50 μg/kg and 20％ in dose of 30 μg/kg) was significantly lower than that of MODS model control group (73.3％) ( P ＜ 0.05 ) and the mortality of mice treated with intraperitoneal 50μg/kg rhEGF (6.7％ ) was lower than that treated with 10μg/kg rhEGF (P=0.014).The mortality of mice in rhEGF MODS (50 μg/kg ) intraperitoneal administration group was significantly lower than that in subcutaneous administration group (40％) (P =0.031 ), The histopathological changes in rhEGF MODS treatment group were not as remarkable as seen in mice of control group.The histopathological changes were dose - dependent.The higher doses of rhEGF,the lesser hepatic congestion,liver cell apoptosis,hepatic cell cloudy swelling and cell vacuolization.Similarly,as RhEGF dosage increased,pulmonary interstitial congestion,inflammatory cells and apoptotic bodies reduced,and bronchial ciliated columnar epithelium less shed.Conclusions RhEGF plays a positive role in repairement of tissue damage in TAA - induced MODS murine model.The rhEGF given by intraperitoneal route of administration is more effective to reduce the 24 h mortality of MODS mice than that by subcutaneous route.
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