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医药导报, 2016, 35(11): 1194-1197
doi: 10.3870/j.issn.1004-0781.2016.11.009
柚皮苷对胃溃疡模型大鼠血清及胃黏膜组织中TFF2含量的影响*
Effect of Naringin on Trefoil Factor 2 Content in Serum and Gastric Mucosal Tissue in Rats with Gastric Ulcer
秦建设, 郑波

摘要: 目的观察柚皮苷对醋酸所致胃溃疡大鼠血清及胃黏膜组织中三叶因子2(TFF2)含量的影响,探讨柚皮苷对胃溃疡的治疗作用。方法将45只SD大鼠随机分成正常对照组,模型对照组,柚皮苷大、小剂量组。除正常对照组外,其他组采用改良Okabe法制作醋酸型胃溃疡模型。造模后次日,模型对照组给予0.9%氯化钠溶液1 mL·(100 g)-1灌胃;柚皮苷小剂量组给予柚皮苷50 mg·kg-1 灌胃;柚皮苷大剂量组给予柚皮苷100 mg·kg-1灌胃。均每天1次,连续给药1周后测量胃溃疡面积,酶联免疫吸附(ELISA)法检测血清与胃黏膜组织TFF2含量。结果与模型对照组比较,柚皮苷小剂量组与大剂量组溃疡指数均明显降低(P<0.01),大鼠血清及胃黏膜TFF2含量明显升高(P<0.05),且大剂量组明显优于小剂量组((P<0.01)。结论柚皮苷具有显著抗大鼠胃溃疡作用,其作用机制可能与提高血清及胃黏膜组织TFF2含量有关。
关键词: 柚皮苷 ; 溃疡,胃 ; 三叶因子2

Abstract:
ObjectiveTo explore the effects of naringin on trefoil factor 2 (TFF2) content in serum and gastric mucosa tissue in gastric ulcer rats induced by acetic acid and its therapeutic effects on gastric ulcer. MethodsForty-five rats were randomly divided into normal control group,model control group and naringin high and low dose groups.The acetic acid gastric ulcer model was established by modified okabe method.On the next day,model control group was given 0.9% sodium chloride solution 1 mL·(100 g)-1,naringin low-dose group was given 50 mg·kg-1, and naringin high-dose group was given 100 mg·kg-1,all by gastric perfusion once-daily for 7 days.Gastric ulcer area was measured,and the contents of TFF2 in serum and gastric mucosa tissue were detected by enzyme linked immunosorbent assay (ELISA). ResultsCompared with the model control group,the ulcer index in naringin treatment groups were significantly decreased (P<0.01),and the contents of TFF2 in serum and gastric mucosa tissue were significantly increased (P<0.05).The high dose group was obviously superior to the low dose group (P<0.01). ConclusionNaringin has significant anti-gastric ulcer effects and the mechanism may be associated with the increased content of TFF2 in serum and gastric mucosa tissue.
Key words: Naringin ; Ulcer,gastric ; Trefoil factor 2

柚皮苷(naringin)是一种双氢黄酮类化合物,为陈皮、枳实、青皮等中药的主要有效成分之一。现代研究表明,柚皮苷具有抗氧化、抗肿瘤、解痉镇痛、降血脂、调节血糖等生物活性和药理作用[1-3]。大量药物成分分析研究显示,对胃溃疡有治疗作用的很多中成药,如健脾舒胃凝胶、胃苏颗粒、胃炎灵颗粒等中成药中均检测出含有大量柚皮苷成分[4-6]。但有关柚皮苷对胃溃疡的直接治疗作用研究文献较少见。为探讨柚皮苷对胃溃疡的治疗作用,进一步明确其抗胃溃疡的作用机制,笔者在本实验中以三叶因子2(trefoil factor 2,TFF2)为研究靶点,观察柚皮苷抗醋酸型胃溃疡的治疗效果及可能的作用途径。

1 材料与方法
1.1 动物

SPF级4个月龄雄性SD大鼠,体质量约200 g,由第三军医大学大坪医院医学实验动物中心提供,生产许可证号:SCXK(渝)2012-0005,饲养室温度25 ℃,相对湿度60%,自由饮水进食。

1.2 试药

柚皮苷(Sigma公司,HPLC法测得纯度≥95%,编号:101291319),TFF2试剂盒(武汉伊莱瑞特生物科技有限公司,编号:AK0014FEB26008)。柚皮苷用羧甲基纤维素钠(CMC)制成100%柚皮苷悬浊液。

1.3 仪器

Bio-Tek ELX800全自动多功能酶标仪(美国宝特),H-1850R湘仪高速离心机(长沙湘仪离心机仪器有限公司)。

1.4 模型的制备与给药

将大鼠采用随机数字表法分为正常对照组9只,模型对照组、柚皮苷小剂量组和柚皮苷大剂量组各12只。适应性饲养1周后禁食不禁水24 h。改良Okabe法制作醋酸型胃溃疡模型[7-8]。造模次日开始给药,模型对照组灌胃给予0.9%氯化钠溶液,1 mL·(100 g)-1;柚皮苷小剂量组灌胃给予柚皮苷50 mg·kg-1;柚皮苷大剂量组灌胃给予柚皮苷100 mg·kg-1。每天 1 次,连续1 周。其余正常饮食。

1.5 标本的采集与处理

给药1周后,所有大鼠禁食24 h,10%水合氯醛腹腔注射麻醉,开腹采用腹主动脉取血方法收集血液标本,取血后室温静置1 h,3 500 r·min-1离心10 min,吸出上层血清存放在-85 ℃冰箱保存。沿胃大弯剪开,以0.9%氯化钠溶液冲洗,观察胃溃疡状况,测量胃溃疡面积。在胃溃疡黏膜处取0.5 mm×0.5 mm组织,4%多聚甲醛固定。余下胃黏膜用组织匀浆器匀浆后离心,吸出上层澄清液在-85 ℃冰箱保存。

1.6 观测指标与方法

1.6.1 溃疡指数(UI) 游标卡尺测量溃疡最长径和最宽径,计算溃疡面积,作为UI。溃疡面积计算方法:S=1/4×L×D×π,公式中L指溃疡长径,D指溃疡短径,π取3.14。

1.6.2 组织病理学 4%多聚甲醛固定的胃黏膜组织标本,24 h后梯度脱水,石蜡包埋,冰冻切片,制成厚5 μm切片,苏木精-伊红(HE)染色,光镜观察。

1.6.3 TFF2测定 采用酶联免疫吸附测定法(ELISA法),按试剂盒说明书检测血清与胃黏膜组织液中TFF2含量。

1.7 统计学方法

采用SPSS 17.0版统计软件,以均数±标准差( x ¯ ±s)表示,组间均数比较采用单因素方差分析,以P<0.05为差异有统计学意义。

2 结果
2.1 动物生物学体征变化

造模后所有动物均单笼饲养。造模后第1天,3组大鼠均出现不同程度踡卧、嗜睡、皮毛突起、不进饮食等情况,第2天起大鼠逐渐开始活动,进食饮水。至取材前,各组大鼠活动、饮食、大小便情况逐步恢复正常,但活跃度、进食量、饮食量等,柚皮苷各剂量组明显较模型对照组好。因伤口感染,术后第2天模型对照组大鼠死亡2只,此后因灌胃操作及护理失误,导致模型对照组和柚皮苷小、大剂量组各死亡1只。

2.2 UI变化与TFF2测定结果

模型对照组、柚皮苷小剂量组和大剂量组均可见明显溃疡面。模型对照组UI为(4.84±0.25) mm2;柚皮苷小剂量组与大剂量组溃疡指数分别为(3.23±0.34),(2.11±0.24) mm2,与模型对照组比较,均明显降低(t=11.81,P<0.01;t=24.84, P<0.01),且柚皮苷大剂量组疗效优于柚皮苷小剂量组(t=8.93,P<0.01)。4组大鼠血清与胃黏膜组织液TFF2测定结果见表1。

表1 4组大鼠血清及胃黏膜组织液TFF2变化
Tab.1 TFF2 variation in the serum and gastric mucosa tissue in four groups of rats pg·mL-1,x¯±s
组别 大鼠/只 血清TFF2 胃黏膜组织TFF2
正常对照组 9 177.67±11.10 196.42±9.16
模型对照组 9 151.15±10.81*1 167.40±13.86*1
柚皮苷
小剂量组 11 164.28±10.28*1*2 179.05±11.28*1*2
大剂量组 11 178.48±13.45*2*3 196.62±10.95*2*3

Compared with normal control group *1P<0.01;compared with model control group *2P<0.01;compared with low-dose naringin group,*3P<0.01

与正常对照组比较,*1P<0.05;与模型对照组比较,*2P<0.05;与柚皮苷小剂量组比较,*3P<0.01

表1 4组大鼠血清及胃黏膜组织液TFF2变化

Tab.1 TFF2 variation in the serum and gastric mucosa tissue in four groups of rats pg·mL-1,x¯±s

2.3 组织病理改变

正常对照组胃黏膜上皮完整,腺体结构整齐均一,未见炎症细胞浸润(图1A)。模型对照组胃黏膜变薄溃烂,上皮缺失严重,腺体排列拥挤紊乱,大量炎症细胞浸润(图1B)。柚皮苷小剂量组胃黏膜局部坏死脱落,腺体排列紊乱,可见明显炎症细胞浸润(图1C)。柚皮苷大剂量组胃黏膜上皮基本完整,局部轻度变性,黏膜下血管扩张充血,少量炎性细胞浸润(图1D)。

图1 4组大鼠胃黏膜病理组织特征(HE染色) A.正常对照组(×10);B.模型对照组(×40);C.柚皮苷小剂量组(×10);D.柚皮苷大剂量组(×10)

Fig.1 Pathology of gastric mucosa in four groups of rats(HE staining) A.normal control group(×10);B.model control group(×40); C.low-dose naringin group(×10);D.high-dose naringin group(×10)

3 讨论

胃溃疡后的修复与愈合也是一个十分复杂的过程,黏膜愈合的质量直接影响到疾病转归。研究表明,胃黏膜修复过程是多种细胞、生长因子及细胞外基质相互作用的复杂过程。而胃黏膜防御屏障功能下降,保护因子减少是形成胃溃疡的重要病理基础。TFF2作为胃黏膜细胞分泌的重要保护因子,在胃溃疡的产生与修复过程中具有重要作用。TFF2是一种具有三叶草型结构域的小分子蛋白质,其与TFF1、TFF3都是TFF家族中最重要的成员。研究表明,TFF主要表达位点在胃肠道,由胃肠道黏膜细胞分泌产生,TFF1、TFF2主要分布在胃窦部,TFF3主要分布在小肠和大肠[9-10]。近年国内外研究显示,TFF2表达部位和含量与胃溃疡关系非常密切,其主要作用机制为:TFF2促进胃黏液糖蛋白分泌,并能与黏液糖蛋白结合生成具有保护作用的复合物,进而避免胃黏膜上皮细胞遭受酸和酶的侵袭,同时能与表皮生长因子、转化生长因子等相关胃黏膜保护因子相互协同,共同促进黏膜上皮细胞向溃疡部位移行和修复[11-13]。此外,相关研究显示,胃癌旁组织和胃癌组织中TFF2表达明显减弱,提示胃癌发生与TFF2表达降低存在明显相关[14-16]

本实验结果表明,柚皮苷具有促进胃溃疡愈合作用。柚皮苷能明显提升胃溃疡大鼠血清及胃黏膜TFF2含量,且大剂量组含量比小剂量组对TFF2促进作用更明显,说明柚皮苷对胃黏膜细胞TFF2含量提升作用可能存在线性相关。UI提示,柚皮苷对胃溃疡修复与愈合具有明显促进作用,这表明柚皮苷对胃溃疡保护作用与提升胃黏膜组织中TFF2含量具有高度相关性。综上所述,柚皮苷治疗胃溃疡作用机制与提高胃黏膜组织中黏膜保护因子TFF2含量有关,通过促进TFF2分泌,加快胃黏膜增殖与修复,从而达到保护胃黏膜、治疗胃溃疡作用。

2013年,柚皮苷被国家批准作为治疗支气管炎的一类新药进入临床试验。本实验研究显示,柚皮苷具有治疗胃溃疡的药理作用,这为进一步深入研究柚皮苷的药理作用提供了新的方法和思路,同时也为治疗胃溃疡提供了一种新的研究途径。

The authors have declared that no competing interests exist.

参考文献

[1] 于广仁,蒋超,肖安风,.柚皮苷及其酶解产物的生物活性研究[J].食品科技,2014,39(3):155-159.
以柚皮苷及其酶解产物柚皮素为考察目标,采用抑菌圈法测定其抑菌活性,通过测定它们对Fe^3+的还原能力、对1,1-二苯-2-苦基苯肼自由基(DPPH·)、羟基自由基(·OH)的清除能力,来评价它们的体外抗氧化性能。抑菌试验结果表明,柚皮苷及柚皮素在相同的试验浓度下,两者的抑菌能力存在着较大差别,柚皮素的抑菌能力要明显强于柚皮苷,且柚皮素对革兰阳性菌的抑制作用要强于革兰阴性菌,但两者对黑曲霉菌未表现出抑制效果。而体外抗氧化试验结果表明,两者在相同浓度下的抗氧化能力也有所不同,柚皮苷、柚皮素及对照物BHT对DPPH自由基的IC50分别为7.044、1.277、0.035mg/mL,对羟自由基的IC50分别为1.499、1.288、1.081mg/mL。
URL    
[本文引用:1]
[2] 谢仁峰,文双娥,李洋,.柚皮苷抗炎镇痛作用的实验研究[J].湖南师范大学学报(医学版),2011,8(4):5-8,12.
目的:观察柚皮苷的抗炎镇痛作用,初步探讨其抗炎作用机制。方法:在小鼠采用腹腔注射乙酸造成急性疼痛、二甲苯导致急性耳肿胀实验和腹腔毛细血管通透性实验模型,观察柚皮苷的抗炎镇痛作用及量效关系。采用大鼠足跖肿胀(蛋清法)实验,测量足跖肿胀度,分光光度法测量组织PGE2水平。结果:柚皮苷能显著减少小鼠扭体次数、耳肿胀度和腹腔渗出液,也能减轻大鼠足跖注射蛋清引起的炎性肿胀,且抗炎强弱与和炎症局部PGE2水平相关(P0.05)。结论:柚皮苷有显著镇痛抗炎效果,抗炎机制可能是其抑制了炎性组织PGE2的合成或释放。
[本文引用:0]
[3] 杨宏亮,田珩,李沛波,.柚皮苷及柚皮素的生物活性研究[J].中药材,2007,30(6):752-754.
篇首: 柚皮苷为芸香科柑橘属植物次生代谢产物.研究表明,柚皮苷及其苷元柚皮素在降血脂、镇静、抗氧化、抗肿瘤、抗真菌、抗动脉粥样硬化等方面具有较强的生物活性.此外,通过与药物代谢酶底物的竞争抑制作用,其还可提高某些药物的口服生物利用度.
[本文引用:1]
[4] 牛晓静,鲁静,段晓颖,.HPLC同时测定健脾舒胃凝胶中甘草苷、柚皮苷、橙皮苷、新橙皮苷、甘草酸铵5种成分含量[J].中国实验方剂学杂志,2015,21(2):77-79.
目的:建立HPLC同时测定健脾舒胃凝胶中甘草苷、柚皮苷、橙皮苷、新橙皮苷、甘草酸铵5种成分含量控制方法。方法:采用Agilent ZORBAX Eclispse SB-C18色谱柱(4.6 mm×150 mm,5μm),流动相乙腈-0.05%磷酸水梯度洗脱,流速1.0 m L·min-1,检测波长237 nm(甘草苷、甘草酸铵),283 nm(柚皮苷、橙皮苷、新橙皮苷)。结果:根据回归方程,甘草苷、柚皮苷、橙皮苷、新橙皮苷、甘草酸铵分别在0.128 3~0.641 6,1.105 2~5.526,0.225 2~1.126 0,1.092~5.460,0.314 9~1.574 4μg进样量与峰面积之间线性关系良好;5个成分的平均回收率分别为101.47%,99.22%,100.02%,101.64%,97.99%(RSD3%)。结论:该方法简便、准确可靠,重复性好,专属性好,分离效果好,适用于健脾舒胃凝胶的质量控制。
DOI:10.13422/j.cnki.syfjx.2015020077      URL    
[本文引用:1]
[5] 杨佳静,薛佳,周华方,.HPLC法同时测定胃苏颗粒中柚皮苷、橙皮苷和新橙皮苷的含量[J].中国药房,2014,25(4):372-374.
目的:建立同时测定胃苏颗粒中柚皮苷、橙皮苷和新橙皮苷含量的方法。方法:采用高效液相色谱法。色谱柱为Agilent Zorbax SB-C18柱,流动相为甲醇-醋酸-水(35∶4∶61,V/V/V),流速为1.0 ml/min,检测波长为283 nm,进样量为5μl,柱温为35℃。结果:柚皮苷、橙皮苷、新橙皮苷检测质量浓度分别在9.413~188.3、4.929~98.59、5.112~102.2μg/ml范围内与峰面积积分值呈良好的线性关系(r=0.999 9);精密度、稳定性、重复性试验的RSD≤1.3%;平均加样回收率分别为101.08%、99.89%、101.46%,RSD分别为0.62%、1.35%、0.45%(n=6)。结论:该方法简便、准确、重复性好,适用于测定胃苏颗粒中3种黄酮苷类成分的含量。
URL    
[本文引用:0]
[6] 张咏梅,陈晓峰,姚莉萍.HPLC 法测定无糖型胃炎灵颗粒中柚皮苷的含量[J].安徽医药,2014,18(6):1045-1047.
目的采用HPLC法测定无糖型胃炎灵颗粒中的柚皮苷。方法色谱柱为SunFire C18,流动相为乙腈—水(22∶78,磷酸调pH=3),检测波长283 nm,流速1.0 mL·min-1,柱温30℃。结果柚皮苷浓度15.56-140.04 mg·L^-1与峰面积的线性关系良好(r=0.999 8),平均加样回收率为98.5%,RSD=1.26%。结论所建方法准确、重复性好,可用于测定无糖型胃炎灵颗粒中的柚皮苷。
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[7] OKABE S,AMAGASE K.An overview of acetic acid ulcer models-the history and state of the art of peptic ulcer research[J].Bio Pharm Bull,2005,28(8):1321-1341.
Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers >100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.
DOI:10.1248/bpb.28.1321      PMID:16079471      URL    
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[8] 才丽平,蒋宁,曲怡,.“毒热证”胃溃疡大鼠模型的制备与评价[J].中华中医药杂志,2011,26(3):416,501-504.
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[9] 张静,吴靖芳,任君旭,.大鼠胃溃疡自愈期间三叶因子2的变化[J].第三军医大学学报,2011,33(13):1358-1361.
目的研究大鼠实验性胃溃疡自愈期间三叶因子2(trefoil factor family 2,TFF2)在血清、胃液和胃黏膜组织中的变化及意义。方法 SD大鼠按随机数字表法分为溃疡组(n=42)、盐水组(n=42)、正常组(n=6),胃前壁黏膜下注射冰乙酸制备大鼠胃溃疡模型,免疫组织化学法检测各组大鼠胃黏膜组织TFF2的表达变化;ELISA法检测各实验组大鼠血清及胃液TFF2变化趋势。结果胃黏膜、血液及胃液检测结果显示在溃疡术后早期(1、2、4、6 d)TFF2增多较为明显。胃黏膜TFF2原位表达以溃疡术后6 d阳性细胞最多(24.50±5.68)(P〈0.01),表达强度较强,可见以壁细胞、颈黏液细胞为主的阳性表达;血清TFF2以溃疡2 d含量最高(338.62±58.72)pmol/L(P〈0.01);胃液TFF2含量以溃疡术后1 d最高(5 021.65±291.69)pmol/L。胃黏膜、血液、胃液TFF2表达量自溃疡术后10 d有所下降,但均高于相应盐水组及正常组(P〈0.05,P〈0.01)。结论 在胃溃疡自愈早期,TFF2在胃黏膜、血液和胃液表达水平均较高,其通过不同的表达途径参与了胃溃疡修复过程。
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[10] MAY F E,SEMPLE J I,NEWTON J L,et al.The human two domain trefoil protein,TFF2,is glycosylated in vivo in the stomach[J].Gut,2000,46(4) :454-459.
Background-TFF2, a member of the trefoil factor family (TFF) of peptides, is a secreted protein of 106 amino acids that is expressed in mucous neck cells of the fundus and glands at the base of the antrum in normal human stomach. TFF2 is also detected at high concentrations around sites of ulceration. It is protective against mucosal damaging agents and stimulates cell motility. Aims-To measure the expression of TFF2 in normal human stomach and its secretion into gastric juice. Methods-TFF2 cDNA was amplified by reverse transcription polymerase chain reaction from gastric mucosa and sequenced. Gastric juice or cytosol, prepared from gastric mucosa, was obtained from individuals with macroscopically normal stomachs. TFF2 concentrations were measured by quantitative western transfer analysis. Results-Sequencing of TFF2 cDNA revealed a single amino acid change from the published sequence. Significant amounts of 12 kDa TFF2 were detected in human gastric juice. Larger quantities of a protein of higher apparent molecular mass were also detected. This was shown to be N-glycosylated TFF2 using the endoglycosidase, peptide-N-Gycosidase F. The majority of TFF2 in normal gastric mucosa was also glycosylated. Conclusions-Human TFF2 is glycosylated via an N-linkage, presumably on Asn
DOI:10.1136/gut.46.4.454      PMID:10716671      URL    
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[11] YU Y,JIA T Z,CAI Q,et al.Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid[J].J Ethnopharmacol,2015,160(3):211-218.
The rhizome of(AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL.The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-伪 (TNF-伪), interleukin 6, 8 (IL-6, 8) and prostaglandin E(PGE) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-伪, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-伪, and IL-8 were examined by immunohistochemistry in stomach.The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-伪, IL-8, IL-6, and PGEand the mRNA expressions of TNF-伪, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective.The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory propertiesdown-regulating TNF-伪, IL-8, IL-6 and PGEand to the gastroprotective effectsup-regulating EGF and TFF2.
DOI:10.1016/j.jep.2014.10.066      PMID:25481080      URL    
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[12] 周学文,周天羽,才丽萍,.三叶因子2在胃黏膜病变中的表达[J].中国中西医结合消化杂志,2010,18(2):95-98.
[目的]观察三叶因子2(TFF2)在胃黏膜病变中的表达及临床意义。[方法]在浅表性胃炎、糜烂性胃炎及胃溃疡3种轻、中、重病变的胃病患者胃黏膜中测定TFF2。观察TFF2在这三个阶段的变化。[结果]TFF2的表达在浅表性胃炎中低、在糜烂性胃炎中次低,在胃溃疡中最低,病情轻重程度与TFF2的表达呈负相关。[结论]TFF2具有保护胃黏膜免受致病因素攻击的作用。
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[13] 秦建设. 补中益气活血方对胃溃疡患者血清TFF2和SOD水平的影响[J].中成药,2015,37(4):735-738.
目的通过观察补中益气活血方(由黄芪、党参、白术、当归、陈皮、升麻、柴胡、炙甘草等组成)对脾胃虚弱型胃溃疡患者血清三叶因子2(TFF2)和超氧化物歧化酶(SOD)表达水平的影响并探讨其可能的机制。方法将符合纳入标准的77例病例随机分为补中益气活血方治疗组(简称中药组)和奥美拉唑治疗组,通过比较2组药物治疗前后的症状分析、胃镜检查、血清TFF2和SOD的水平来观察对胃溃疡的治疗效果。结果治疗后,补中益气活血方组的临床疗效评定和提升胃溃疡患者血清TFF2和SOD的表达水平明显优于奥美拉唑组(P〈0.05)。结论补中益气活血方抗脾胃虚弱型胃溃疡的作用机理可能与调节胃黏膜中TFF2和SOD的表达有关。
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[14] 尹香利,闫育平.三叶因子表达规律与胃组织癌化进程的关系[J].疑难病杂志,2013,12(9):694-696.
目的 探讨三叶因子的表达规律对判断胃癌恶化进程的临床意义.方法 采用免疫组化染色SP法对胃镜活检标本228例进行检测,其中正常胃黏膜40例,肠上皮化生60例,不典型增生48例,胃癌80例.统计分析胃组织病变演 化至肠上皮化生、不典型增生及胃癌的过程中,三叶因子I、II、III(TFF1、TFF2、TFF3)的阳性表达情况及其与胃癌临床病理特征的关系.结 果 在正常胃黏膜演变成胃癌过程中,TFF1、TFF2的表达强度逐渐递减(P0.05);TFF3在不同分化程度中的阳性表达无显著 性差异(P>0.05),在不同TNM分期中有明显差异(P<0.05).结论 三叶因子的表达能够客观反映正常胃黏膜演变成胃癌的恶化过程,对诊疗胃癌具有重要的临床指导意义.
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[15] 石磊,赖铭裕,梁志海,.TFF2在胃癌、癌旁及正常胃黏膜组织中的表达及其与血管生成的关系[J].世界华人消化杂志,2011,19(3):246-250.
目的:探讨三叶因子2(TFF2)、血管内皮生长因子(VEGF)和微血管密度(MVD)在胃癌发生、发展、浸润和转移中的作用.方法:选取广西医科大学第一附属医院2008-01/2009-06接受胃大部切除术的胃癌标本50例,采用SP免疫组织化学方法检测30例正常胃黏膜组织、50例癌旁组织和50例胃癌组织中TFF2、VEGF和MVD的表达情况.结果:正常胃黏膜组织→癌旁组织→胃癌组织中,TFF2表达呈逐渐减弱趋势(165.80±16.42,184.44±19.02,206.79±17.62,均P0.01),TFF2的表达与肿瘤的分化程度和淋巴结转移有关(均P0.01),而VEGF的表达和MVD值呈逐渐上升趋势(36.7%,42.0%,72.6%;26.35±4.54,30.78±5.64,40.13±6.92,均P0.01),两者表达与肿瘤的分化程度、浸润深度和淋巴结转移有关(均P0.01).TFF2与MVD的表达呈负相关(r=-0.781,P0.01).结论:TFF2作为一种胃癌的抑制因子,在胃癌发展过程中表达逐渐减弱,对胃癌的抑制作用降低,同时一些促进肿瘤浸润转移的因子如VEGF、MVD表达水平逐渐增强,促进了肿瘤的发展转移.
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[16] 荣芳,王勇,王满贵,.TFF2在胃癌中的表达及与幽门螺杆菌感染关系的研究[J].中国微生态学杂志,2011,23(4):293-297.
目的 探讨三叶因子Ⅱ(Trefoil factors2,TFF2)在胃癌和癌前病变中的表达及与幽门螺杆菌感染(Helicobacter pylori,H.pylori)的关系.方法 选取经病理证实的慢性浅表性胃炎、胃溃疡、慢性萎缩性胃炎和胃癌4种不同胃黏膜病变的标本140例,用免疫组化法检测标本中TFF2的表达及 H.pylori的感染情况,并分析TFF2的表达与H.pylori的感染的关系.结果 在慢性浅表性胃炎、胃溃疡、慢性萎缩性胃炎和胃癌中,TFF2和H.pylori的表达率依序呈逐渐增加的趋势,但TFF2在胃癌组织中表达降 低.H.pylori阳性组TFF2的表达率低于阴性组,TFF2的阳性率与H.pylori感染率之间呈负相关(r=-0.335,P< 0.05).结论 TFF2的表达和H.pylori的感染与肿瘤的发生密切相关,检测该指标可为胃癌诊断、判断预后和指导治疗提供理论依据.
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关键词(key words)
柚皮苷
溃疡,胃
三叶因子2

Naringin
Ulcer,gastric
Trefoil factor 2

作者
秦建设
郑波

QIN Jianshe
ZHENG Bo