表皮生长因子对葡聚糖硫酸钠诱导的结肠炎模型小鼠肠道损伤的修复研究
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摘要
本文旨在讨论表皮生长因子(EGF)对葡聚糖硫酸钠(DSS)诱导的结肠炎模型小鼠肠道损伤的修复作用。选用24只6周龄BALB/c小鼠,随机分为3组,即:正常对照组、DSS模型对照组、DSS+EGF组。正常对照组小鼠饮用自来水;DSS模型对照组小鼠在试验第1~7天饮用5%DSS水溶液,第8~10天饮用自来水;DSS+EGF组小鼠按照DSS模型对照组处理,同时每天皮下注射EGF 2次,共注射10 d。结果表明:1)与正常对照组相比,DSS模型对照组小鼠结肠长度极显著降低(P<0.01);与DSS模型对照组相比,DSS+EGF组小鼠结肠长度极显著增加(P<0.01)。2)DSS模型对照组小鼠结肠可见典型溃疡,结肠损伤程度评分(CDS)极显著高于正常对照组(P<0.01);DSS+EGF组小鼠结肠组织未见溃疡,与DSS模型对照组相比,CDS极显著降低(P<0.01)。3)与正常对照组相比,DSS模型对照组小鼠结肠紧密连接蛋白(Occludin)浓度显著降低(P<0.05);与DSS模型对照组相比,DSS+EGF组小鼠结肠Occludin浓度显著升高(P>0.05)。4)与正常对照组相比,DSS模型对照组小鼠结肠白细胞介素-2(IL-2)和白细胞介素-4(IL-4)浓度极显著降低(P<0.01),白细胞介素-10(IL-10)浓度显著降低(P<0.05);与DSS模型对照组相比,DSS+EGF组结肠IL-2和IL-4浓度极显著增加(P<0.01),IL-10浓度显著增加(P<0.05)。由此可见,EGF可能通过提高肠道Occludin表达水平,调节肠道细胞因子浓度趋于正常水平,从而修复受损肠道组织,维持肠道黏膜屏障的完整性。
This study aimed to evaluate the effects of intestinal damage repair of epidermal growth factor( EGF) on dextra sulfate sodium( DSS)-induced colitis in mice. Twenty-four BALB /C mice aged at 6 weeks were randomly assigned into three groups: normal control group,DSS model control group and DSS + EGF group. The normal control group received normal drinking water; DSS model control group received 5% DSS solution in drinking water for 7 consecutive days and follow ed with normal drinking water for 3 days; DSS +EGF group received the same treatment of DSS as DSS model control group,meanw hile,these mice were administered with EGF by intraperitoneal injection tw ice a day and for 10 days. The results showed as follow s:1) DSS model control group significantly shortened colon length of mice compared with the normal control group( P< 0.01),and DSS + EGF group significantly increased colon length of mice compared with the DSS model control group( P< 0.01). 2) Mice in DSS model control group revealed a typical ulcer of the colonic tissues,and significant increased colonic damage score( CDS) compared with the normal control group( P <0.01). Mice in DSS +EGF group did not show the ulcer of the colonic tissues,and significantly reduced CDS compared with DSS model control group( P< 0.01). 3) DSS model control group significantly decreased colonic tight junction proteins( Occludin) concentration of mice compared with normal control group( P< 0.05).DSS + EGF group significantly increased colonic Occludin concentration of mice compared with DSS model control group( P< 0. 05). 4) DSS model control group significantly decreased colonic interleukin( IL)-2( P <0.01),IL-4( P< 0. 01) and IL-10 concentrations( P < 0. 05) of mice compared with normal control group.DSS +EGF group significantly increased colonic IL-2( P < 0. 01),IL-4( P < 0. 01) and IL-10 concentrations( P<0.05) of mice compared with DSS model control group.The results show that EGF can repair damaged intestinal tissue and maintain the integrity of the intestinal mucosal barrier by increasing intestinal Occludin expression and regulation of levels of intestinal cytokines concentrations.
This study aimed to evaluate the effects of intestinal damage repair of epidermal growth factor( EGF) on dextra sulfate sodium( DSS)-induced colitis in mice. Twenty-four BALB /C mice aged at 6 weeks were randomly assigned into three groups: normal control group,DSS model control group and DSS + EGF group. The normal control group received normal drinking water; DSS model control group received 5% DSS solution in drinking water for 7 consecutive days and follow ed with normal drinking water for 3 days; DSS +EGF group received the same treatment of DSS as DSS model control group,meanw hile,these mice were administered with EGF by intraperitoneal injection tw ice a day and for 10 days. The results showed as follow s:1) DSS model control group significantly shortened colon length of mice compared with the normal control group( P< 0.01),and DSS + EGF group significantly increased colon length of mice compared with the DSS model control group( P< 0.01). 2) Mice in DSS model control group revealed a typical ulcer of the colonic tissues,and significant increased colonic damage score( CDS) compared with the normal control group( P <0.01). Mice in DSS +EGF group did not show the ulcer of the colonic tissues,and significantly reduced CDS compared with DSS model control group( P< 0.01). 3) DSS model control group significantly decreased colonic tight junction proteins( Occludin) concentration of mice compared with normal control group( P< 0.05).DSS + EGF group significantly increased colonic Occludin concentration of mice compared with DSS model control group( P< 0. 05). 4) DSS model control group significantly decreased colonic interleukin( IL)-2( P <0.01),IL-4( P< 0. 01) and IL-10 concentrations( P < 0. 05) of mice compared with normal control group.DSS +EGF group significantly increased colonic IL-2( P < 0. 01),IL-4( P < 0. 01) and IL-10 concentrations( P<0.05) of mice compared with DSS model control group.The results show that EGF can repair damaged intestinal tissue and maintain the integrity of the intestinal mucosal barrier by increasing intestinal Occludin expression and regulation of levels of intestinal cytokines concentrations.
引文
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[19]王少鑫,浦江,刘超群,等.炎症因子TNF-α、IL-6和IL-4在溃疡性结肠炎中的表达及临床意义[J].胃肠病学和肝病学杂志,2015,24(1):104-106.
[20]DHARMANI P,LEUNG P,CHADEE K.Tumor necrosis factor-αand M uc2 mucin play major roles in disease onset and progression in dextran sodium sulphateinduced colitis[J].PLo S One,2011,6(9):e25058.
[21]温红珠,郝薇薇,李佳,等.葡聚糖硫酸钠结肠炎模型影响因素的研究进展[J].世界华人消化杂志,2011,19(36):3666-3671.
[22]郭建生,湛扩,彭宇,等.肠炎愈片对大鼠溃疡性结肠炎血清白介素-2、一氧化氮的影响研究[J].湖南中医药大学学报,2007,27(6):18-20.
[23]张歆,柯晓,陈锦团,等.IL-1β、IL-4在湿热证溃疡性结肠炎大鼠模型中的动态表达及意义[J].西安交通大学学报:医学版,2015,36(5):697-701.
[24]BERG D J,DAVIDSON N,KHN R,et al.Enterocolitis and colon cancer in interleukin-10-deficient mice are associated w ith aberrant cytokine production and CD+4TH1-like responses[J].Journal of Clinical Investigation,1996,98(4):1010-1020.
[2]BISCHOFF S C,BARBARA G,BUURMAN W,et al.Intestinal permeability-a new target for disease prevention and therapy[J].BM C Gastroenterology,2014,14(1):189.
[3]CARPENTER G,COHEN S.Epidermal growth factor[J].The Journal of Biological Chemistry,1990,265(14):7709-7712.
[4]PLAYFORD R J,WRIGHT N A.Why is epidermal grow th factor present in the gut lumen?[J].Gut,1996,38(3):303-305.
[5]JUNG K,KANG B K,KIM J Y,et al.Effects of epidermal grow th factor on atrophic enteritis in piglets induced by experimental porcine epidemic diarrhoea virus[J].The Veterinary Journal,2008,177(2):231-235.
[6]BOONSTRA J,RIJKEN P,HUMBEL B,et al.The epidermal grow th factor[J].Cell Biology International,1995,19(5):413-430.
[7]李超,郭春华,刘棋,等.猪表皮生长因子及其应用前景[J].畜牧与兽医,2009,41(12):93-96.
[8]MIETTINEN P J,BERGER J E,MENESES J,et al.Epithelial immaturity and multiorgan failure in mice lacking epidermal grow th factor receptor[J].Nature,1995,376(6538):337-341.
[9]DIELEMAN L A,PALMEN M J,AKOL H,et al.Chronic experimental colitis induced by dextran sulphate sodium(DSS)is characterized by Th1 and Th2cytokines[J].Clinical&Experimental Immunology,1998,114(3):385-391.
[10]刘淑杰,徐子伟,齐珂珂,等.表皮生长因子对肠道功能调控的研究[J].动物营养学报,2014,26(3):565-570.
[11]汤小朋,方热军.表皮生长因子对早期断奶仔猪生长性能及肠道健康的影响[J].动物营养学报,2015,27(11):3345-3351.
[12]AVISSAR N E,TOIA L,SAX H C.Epidermal growth factor and/or grow th hormone induce differential,side-specific signal transduction protein phosphorylation in enterocytes[J].Journal of Parenteral and Enteral Nutrition,2005,29(5):322-336.
[13]BERSETH C L.Enhancement of intestinal growth in neonatal rats by epidermal grow th factor in milk[J].American Journal of Physiology,1987,253(5):G662-G665.
[14]秦环龙,高志光.肠上皮细胞紧密连接在肠屏障中的作用研究进展[J].世界华人消化杂志,2005,13(4):443-447.
[15]MIR H,MEENA A S,CHAUDHRY K K,et al.Occludin deficiency promotes ethanol-induced disruption of colonic epithelial junctions,gut barrier dysfunction and liver damage in mice[J].Biochimica et Biophysica Acta:General Subjects,2016,1860(4):765-774.
[16]GENG Y X,LI J S,WANG F,et al.Epidermal growth factor promotes proliferation and improves restoration after intestinal ischemia-reperfusion injury in rats[J].Inflammation,2013,36(3):670-679.
[17]CRIBBS R K,HARDING P A,LUQUETTE M H,et al.Endogenous production of heparin-binding EGF-like grow th factor during murine partial-thickness burn w ound healing[J].Journal of Burn Care&Rehabilitation,2002,23(2):116-225.
[18]TORRES M I,ROS A.Current view of the immunopathogenesis in inflammatory bow el disease and its implications for therapy[J].World Journal of Gastroenterology,2008,14(13):1972-1980.
[19]王少鑫,浦江,刘超群,等.炎症因子TNF-α、IL-6和IL-4在溃疡性结肠炎中的表达及临床意义[J].胃肠病学和肝病学杂志,2015,24(1):104-106.
[20]DHARMANI P,LEUNG P,CHADEE K.Tumor necrosis factor-αand M uc2 mucin play major roles in disease onset and progression in dextran sodium sulphateinduced colitis[J].PLo S One,2011,6(9):e25058.
[21]温红珠,郝薇薇,李佳,等.葡聚糖硫酸钠结肠炎模型影响因素的研究进展[J].世界华人消化杂志,2011,19(36):3666-3671.
[22]郭建生,湛扩,彭宇,等.肠炎愈片对大鼠溃疡性结肠炎血清白介素-2、一氧化氮的影响研究[J].湖南中医药大学学报,2007,27(6):18-20.
[23]张歆,柯晓,陈锦团,等.IL-1β、IL-4在湿热证溃疡性结肠炎大鼠模型中的动态表达及意义[J].西安交通大学学报:医学版,2015,36(5):697-701.
[24]BERG D J,DAVIDSON N,KHN R,et al.Enterocolitis and colon cancer in interleukin-10-deficient mice are associated w ith aberrant cytokine production and CD+4TH1-like responses[J].Journal of Clinical Investigation,1996,98(4):1010-1020.