蛋白酶激活受体2在早期断奶仔猪胃肠黏膜屏障中作用研究
|
摘要
蛋白酶激活受体-2(protease-activated receptor-2, PAR-2)属于G蛋白偶联受体,研究显示PAR-2广泛存在于动物的胃肠道组织中,具有介导和抵抗炎症的作用,对胃肠道疾病有重要的调节作用。断奶仔猪腹泻(Diarrhea of weaning piglets,PWD)是仔猪在断奶期间由多种因素引起的腹泻病的总称,仔猪断奶腹泻有发病率高、致死率高的特点,严重危害养猪业的发展。本试验把PAR-2和断奶仔猪腹泻病联系起来,为了阐明PAR-2与断奶仔猪胃肠道粘膜屏障的关系,从而了解PAR-2在仔猪腹泻病理过程中的作用,为防治“仔猪早期断奶综合征”提供一定的依据。本实验从以下列两个方面进行了分析研究。
1.PAR-2与胃肠粘膜系统在断奶仔猪腹泻过程中相关性研究
以体重为(10±0.3)kg,25-28日龄的30头早期断奶仔猪为研究对象,对其中的18头断奶仔猪每头口服接种1.0×1011cfu/ml的ETEC大肠杆菌5ml而建立腹泻模型。选取其中腹泻比较明显的12头仔猪作为腹泻组,12头健康仔猪作为正常组。在仔猪腹泻的第1d、3d、5d和第7d屠宰仔猪,采集样品。取腹泻组与正常组仔猪的胃肠道组织,利用HE染色观察胃肠道组织的病理学变化；采用免疫组化、Western Blotting及荧光定量PCR技术观察PAR-2、Claudin-1、Occludin及ZO-1mRNA和蛋白水平上的变化；利用ELISA技术检测血浆中CGRP、IL-6和TNF-α的含量变化,利用生化试验检测组织匀浆中磷脂、氨基己糖和血浆中内毒素、DAO的含量变化。结果显示腹泻仔猪病理组织学变化主要表现为胃肠道粘膜上皮细胞脱落坏死,肠道粘膜层及平滑肌变薄,损伤严重的粘膜固有层内有嗜酸性粒细胞及嗜中性粒细胞浸润,肠绒毛凌乱等。PAR-2在整个胃肠道中都有表达,腹泻第3d的PAR-2蛋白与正常组相比表达量增加(P<0.05),强阳性反应主要存在于粘膜固有层的上皮细胞的顶端,血管上皮细胞,腺细胞的基底部,嗜酸性粒细胞及中性粒细胞等,所有的对照组均无阳性反应。PAR-2 mRNA在腹泻的第1d、3d、5d和第7d都有明显的增加,且在回肠和结肠中更明显。随着腹泻时间的延长,Claudin-1、Occludin及ZO-1在蛋白和基因水平上都有明显的变化,三种蛋白在回肠和结肠变化差异显著,提示随着腹泻时间的延长,胃肠粘膜的损伤越严重,但肠道更为显著。在仔猪腹泻的第3d胃黏膜组织中氨基己糖与正常组相比含量降低(P<0.05),而第1d、第5d及第7d不显著,且均低于正常组。磷脂在腹泻的第3d和第5d比正常组低(P<0.05),而第1d和第7d差异不显著,且均低于正常组。腹泻组仔猪随着腹泻时间的延长,血浆中内毒素、TNF-α、IL-6及DAO的含量都显著或极显著升高。在仔猪腹泻的第3-7d,上述各指标与正常对照组相比含量都明显增加(P<0.01),而在腹泻的第1d,内毒素、DAO虽然高于对照组(P>0.05)。CGRP与对照组相比,第1d和第5d差异不显著,第3d和第7d血浆中的含量明显降低(P<0.05),且均明显降低。这部分实验结果提示PAR-2与仔猪胃肠道粘膜系统呈负相关。
2.PAR-2对猪小肠上皮细胞IL-6、IL-8的分泌以及TJ连接蛋白的影响研究
取新生仔猪小肠组织,采用酶消化法培养原代小肠上皮细胞,再进过纯化传代培养形成单层细胞,在细胞中添加胰蛋白酶、大豆蛋白酶抑制剂、人工合成PAR-2激动剂SLIGRL-NH2、LRGILS-NH2、LPS及LT刺激剂,在刺激时间分别为2h、14h和24h时,利用ELISA法检测猪小肠上皮细胞细胞上清液中IL-6、IL-8的含量,利用荧光定量PCR技术检测PAR-2、Claudiri-1、Occludin及ZO-1 mRNA水平的变化。结果显示,对照组中小肠上皮细胞释放IL-6和IL-8的量很低几乎可以忽略不计,但是在PAR-2激动剂(胰蛋白酶和SLIGRL-NH2)刺激猪小肠上皮细胞释放IL-6和IL-8,并且在LPS及LT存在的情况下释放量更显著。在刺激24h后,PAR-2激动剂组IL-6和IL-8的含量与正常组相比明显升高(P<0.05),且有LPS+LT存在时IL-8的含量更高于正常组(P<0.01)。Claudin-1、Occludin及ZO-1 mRNA在PAR-2激动剂刺激作用24h后,表达量明显低于空白对照、反激动肽、大豆蛋白酶抑制剂组,(P<0.05)其中Claudin-1变化最为明显。
以上的结果提示,PAR-2对胃肠道粘膜屏障有负调控作用,在断奶仔猪腹泻病理过程中有一定介导作用。激活后的PAR-2可以促进炎性细胞因子的产生,炎性因子的高表达又可以使中性粒细胞、嗜酸性粒细胞等炎性细胞迁移,从而调解胃肠道炎症反应。而且炎性细胞因子浓度的变化可以使Claudin-1、Occludin及ZO-1三种TJ连接蛋白表达量降低,移位等,导致而TJ结构受损,破坏上皮细胞的屏障作用。
The protease-activated receptor-2 (PAR-2) is a member of the G-protein-coupled receptor family. Studies have shown that PAR-2 has a wide tissue expression in the gastrointestinal tract of animals and sugested to be anti-inflammatory and pro-inflammatory. PAR-2 has an important regulatory role in the gastrointestinal diseases. Diarrhea of weaning piglets (PWD) is a combination of factors caused diarrhea during the weaning period. PWD have characteristics of high morbidity and mortality, this characterixeics are severely detrimental to the porcine industry. In this study, we linked the PAR-2 and PWD, represented the relationship between PAR-2 and the gastrointestinal mucosal barrier of weaned piglets, understanded the role of PAR-2 in the diarrhea pathological process, got a new way for healing the PWD. The following two aspestes have been studied and analyzed in this study.
The investigative object were 30 Duroc piglets aged 25-28 days and weighing (10±0.3)kg,18 piglets were infected with Enterotoxigenic E.coli (ECET) 5.0×1011 CFU oral dose.12 piglets with diarrhea were selected as a diarrhea group,12 healthy piglets as normal group. The piglets were abataged and collected the samples in the diarrhea 1th、3th、5th and 7th days(three healthy and three diarrhea piglets every time). Conventional methods were used to get the gastrointestinal tissues and blood from healthy and diarrhea piglets. HE staining was used to survey pathological changes in GI tracts Immunohistochemistry、Western Blotting and SYBR Green real-time RT-PCR were used to observe expression difference of PAR-2、Claudin-1、Occludin and ZO-1 at the level of genes and proteins; ELISA was used to test the concentration of CGRP、IL-6 and TNF-αin blood plasma; Conventional biochemical experiments were usd to test the concentration of phosphatide、aminohexose、endotoxin and DAO.
The results showed that most pathological changes showed desquamation and denaturation in the epithelium mucosae, smooth muscle thinning of bowels, infiltrated neutrophil and eosinophil in the lamina propria, and lymph nodules were hyperplasia in submucosa. PAR-2 was expressed in all GI, there were significant differences between healthy and diarrhea group at the 3th day(P<0.05). Strong positive reaction occurs mainly in the epithelial cells of the lamina propria mucosa at the top of the epithelial cells of the blood vessels, rinsing basal parts, eosinophilic and neutrophils etc, all of the control group had positive reaction. There had been a marked increase of PAR-2 mRNA at the 3th、5th and 7th days, especially in ileum and colon. With the extension of diarrhea time, Claudin-1、Occludin and ZO-1 had obvious changes in the level of protein and gene, especially in intestinal tract, these results suggested that as the extension of diarrhea time, the more serious damage of the gastrointeseinal mucous, the ETEC major damage gut. In the third day, the density of aminohexose was decresed markly in the diarrhea group, and had significant difference compared with the normal group(P< 0.05), but the disparity was not signigicant in the 1th、5th and 7th days. Phospholipid also was decresed,signigicant difference in the 3th and 5th days, but not signigicant in the 1th and 7th days. With the extension of diarrhea time, the levels of endotoxin、TNF-α、IL-6 and DAO were signigicantly or very significantly increased in the plasma from diarrhea. In the 3-7th days, the above indexes difference were signigicantly comparaed with the control group(P<0.01), although the density of endotoxin and DAO were increased, but no signigicant differences(P>0.05). Compared with the control group, the density of CGRP were decreased, significant difference in the 5th and 7th days(P< 0.05), no dignificant difference in the 1th and 7th days(P>0.05). This part of the experimental results suggested that the was a negative correlation between PAR-2 and gastrointestinal mucosa system.
The small intestine tissue were separated from newborn piglet, and cultured the intestinal epithelial cells(IEC) using enzymatic digestion, then got the cell monolayer after purification. A variety of stimulants were added in the medium of IEC, which included trypsin、soybean protease inhibitor、synthetic PAR-2 agonist SLIGRL-NH2、LRGILS-NH2、LPS and LT. In the action time was 2h、14h and 24h, ELISA was used to test the concentration of IL-6 and IL-8 in supernatant of cells; SYBR Green real-time RT-PCR was used to observe expression difference of Claudin-1、Occludin and ZO-1 mRNA. The data shown that Non-activated IECs produced negligible amounts of IL-6 and IL-8. Incubation of IECs with a PAR-2 agonist resulted in a low, but significant increase in IL-6 and IL-8 expression compared with controls. To examine the possible synergy between PAR-2 agonists and LPS+LT on IEC activation, IECs were incubated with trypsin and SLIGKV-NH2 in the presence concentrations of LPS+LT Incubation of IECs with the PAR-2 agonists in the presence of LPS+LT resulted in marked potentiation of IL-6 and IL-8 production at all concentrations tested. The change in IL-8 expression was more pronounced to that of IL-6. In the PAR-2 agonist stimulation 24h, the expression of Claudin-1、Occludin and ZO-1 mRNA was significantly lower than the group of control、soybean protease inhibitor and LRGILS-NH2, the difference was significant(P<0.05) which Claudin-1 change was evident.
Above results suggested that PAR-2 had a negative regulation role on gasrointestinal mucosal barrier, and had a certain medium in the pathogenesis of diarrhea in weaned piglets. PAR-2 can promote the production of inflammatory cytokines after activation. The high wxpression of inglammatory factors can make neutrophils、eosinophils and other inflammatory cell migration to mediate inflammation in the gastrointestinal tract. Changes in the concentration of inflammatory cytokines can make the of expression decreased and shift of the three TJ proteins of Claudin-1、Occludin and ZO-1, resulting in structural damage of TJ and influenced the barrier function of epithelial cell.
1.PAR-2与胃肠粘膜系统在断奶仔猪腹泻过程中相关性研究
以体重为(10±0.3)kg,25-28日龄的30头早期断奶仔猪为研究对象,对其中的18头断奶仔猪每头口服接种1.0×1011cfu/ml的ETEC大肠杆菌5ml而建立腹泻模型。选取其中腹泻比较明显的12头仔猪作为腹泻组,12头健康仔猪作为正常组。在仔猪腹泻的第1d、3d、5d和第7d屠宰仔猪,采集样品。取腹泻组与正常组仔猪的胃肠道组织,利用HE染色观察胃肠道组织的病理学变化；采用免疫组化、Western Blotting及荧光定量PCR技术观察PAR-2、Claudin-1、Occludin及ZO-1mRNA和蛋白水平上的变化；利用ELISA技术检测血浆中CGRP、IL-6和TNF-α的含量变化,利用生化试验检测组织匀浆中磷脂、氨基己糖和血浆中内毒素、DAO的含量变化。结果显示腹泻仔猪病理组织学变化主要表现为胃肠道粘膜上皮细胞脱落坏死,肠道粘膜层及平滑肌变薄,损伤严重的粘膜固有层内有嗜酸性粒细胞及嗜中性粒细胞浸润,肠绒毛凌乱等。PAR-2在整个胃肠道中都有表达,腹泻第3d的PAR-2蛋白与正常组相比表达量增加(P<0.05),强阳性反应主要存在于粘膜固有层的上皮细胞的顶端,血管上皮细胞,腺细胞的基底部,嗜酸性粒细胞及中性粒细胞等,所有的对照组均无阳性反应。PAR-2 mRNA在腹泻的第1d、3d、5d和第7d都有明显的增加,且在回肠和结肠中更明显。随着腹泻时间的延长,Claudin-1、Occludin及ZO-1在蛋白和基因水平上都有明显的变化,三种蛋白在回肠和结肠变化差异显著,提示随着腹泻时间的延长,胃肠粘膜的损伤越严重,但肠道更为显著。在仔猪腹泻的第3d胃黏膜组织中氨基己糖与正常组相比含量降低(P<0.05),而第1d、第5d及第7d不显著,且均低于正常组。磷脂在腹泻的第3d和第5d比正常组低(P<0.05),而第1d和第7d差异不显著,且均低于正常组。腹泻组仔猪随着腹泻时间的延长,血浆中内毒素、TNF-α、IL-6及DAO的含量都显著或极显著升高。在仔猪腹泻的第3-7d,上述各指标与正常对照组相比含量都明显增加(P<0.01),而在腹泻的第1d,内毒素、DAO虽然高于对照组(P>0.05)。CGRP与对照组相比,第1d和第5d差异不显著,第3d和第7d血浆中的含量明显降低(P<0.05),且均明显降低。这部分实验结果提示PAR-2与仔猪胃肠道粘膜系统呈负相关。
2.PAR-2对猪小肠上皮细胞IL-6、IL-8的分泌以及TJ连接蛋白的影响研究
取新生仔猪小肠组织,采用酶消化法培养原代小肠上皮细胞,再进过纯化传代培养形成单层细胞,在细胞中添加胰蛋白酶、大豆蛋白酶抑制剂、人工合成PAR-2激动剂SLIGRL-NH2、LRGILS-NH2、LPS及LT刺激剂,在刺激时间分别为2h、14h和24h时,利用ELISA法检测猪小肠上皮细胞细胞上清液中IL-6、IL-8的含量,利用荧光定量PCR技术检测PAR-2、Claudiri-1、Occludin及ZO-1 mRNA水平的变化。结果显示,对照组中小肠上皮细胞释放IL-6和IL-8的量很低几乎可以忽略不计,但是在PAR-2激动剂(胰蛋白酶和SLIGRL-NH2)刺激猪小肠上皮细胞释放IL-6和IL-8,并且在LPS及LT存在的情况下释放量更显著。在刺激24h后,PAR-2激动剂组IL-6和IL-8的含量与正常组相比明显升高(P<0.05),且有LPS+LT存在时IL-8的含量更高于正常组(P<0.01)。Claudin-1、Occludin及ZO-1 mRNA在PAR-2激动剂刺激作用24h后,表达量明显低于空白对照、反激动肽、大豆蛋白酶抑制剂组,(P<0.05)其中Claudin-1变化最为明显。
以上的结果提示,PAR-2对胃肠道粘膜屏障有负调控作用,在断奶仔猪腹泻病理过程中有一定介导作用。激活后的PAR-2可以促进炎性细胞因子的产生,炎性因子的高表达又可以使中性粒细胞、嗜酸性粒细胞等炎性细胞迁移,从而调解胃肠道炎症反应。而且炎性细胞因子浓度的变化可以使Claudin-1、Occludin及ZO-1三种TJ连接蛋白表达量降低,移位等,导致而TJ结构受损,破坏上皮细胞的屏障作用。
The protease-activated receptor-2 (PAR-2) is a member of the G-protein-coupled receptor family. Studies have shown that PAR-2 has a wide tissue expression in the gastrointestinal tract of animals and sugested to be anti-inflammatory and pro-inflammatory. PAR-2 has an important regulatory role in the gastrointestinal diseases. Diarrhea of weaning piglets (PWD) is a combination of factors caused diarrhea during the weaning period. PWD have characteristics of high morbidity and mortality, this characterixeics are severely detrimental to the porcine industry. In this study, we linked the PAR-2 and PWD, represented the relationship between PAR-2 and the gastrointestinal mucosal barrier of weaned piglets, understanded the role of PAR-2 in the diarrhea pathological process, got a new way for healing the PWD. The following two aspestes have been studied and analyzed in this study.
The investigative object were 30 Duroc piglets aged 25-28 days and weighing (10±0.3)kg,18 piglets were infected with Enterotoxigenic E.coli (ECET) 5.0×1011 CFU oral dose.12 piglets with diarrhea were selected as a diarrhea group,12 healthy piglets as normal group. The piglets were abataged and collected the samples in the diarrhea 1th、3th、5th and 7th days(three healthy and three diarrhea piglets every time). Conventional methods were used to get the gastrointestinal tissues and blood from healthy and diarrhea piglets. HE staining was used to survey pathological changes in GI tracts Immunohistochemistry、Western Blotting and SYBR Green real-time RT-PCR were used to observe expression difference of PAR-2、Claudin-1、Occludin and ZO-1 at the level of genes and proteins; ELISA was used to test the concentration of CGRP、IL-6 and TNF-αin blood plasma; Conventional biochemical experiments were usd to test the concentration of phosphatide、aminohexose、endotoxin and DAO.
The results showed that most pathological changes showed desquamation and denaturation in the epithelium mucosae, smooth muscle thinning of bowels, infiltrated neutrophil and eosinophil in the lamina propria, and lymph nodules were hyperplasia in submucosa. PAR-2 was expressed in all GI, there were significant differences between healthy and diarrhea group at the 3th day(P<0.05). Strong positive reaction occurs mainly in the epithelial cells of the lamina propria mucosa at the top of the epithelial cells of the blood vessels, rinsing basal parts, eosinophilic and neutrophils etc, all of the control group had positive reaction. There had been a marked increase of PAR-2 mRNA at the 3th、5th and 7th days, especially in ileum and colon. With the extension of diarrhea time, Claudin-1、Occludin and ZO-1 had obvious changes in the level of protein and gene, especially in intestinal tract, these results suggested that as the extension of diarrhea time, the more serious damage of the gastrointeseinal mucous, the ETEC major damage gut. In the third day, the density of aminohexose was decresed markly in the diarrhea group, and had significant difference compared with the normal group(P< 0.05), but the disparity was not signigicant in the 1th、5th and 7th days. Phospholipid also was decresed,signigicant difference in the 3th and 5th days, but not signigicant in the 1th and 7th days. With the extension of diarrhea time, the levels of endotoxin、TNF-α、IL-6 and DAO were signigicantly or very significantly increased in the plasma from diarrhea. In the 3-7th days, the above indexes difference were signigicantly comparaed with the control group(P<0.01), although the density of endotoxin and DAO were increased, but no signigicant differences(P>0.05). Compared with the control group, the density of CGRP were decreased, significant difference in the 5th and 7th days(P< 0.05), no dignificant difference in the 1th and 7th days(P>0.05). This part of the experimental results suggested that the was a negative correlation between PAR-2 and gastrointestinal mucosa system.
The small intestine tissue were separated from newborn piglet, and cultured the intestinal epithelial cells(IEC) using enzymatic digestion, then got the cell monolayer after purification. A variety of stimulants were added in the medium of IEC, which included trypsin、soybean protease inhibitor、synthetic PAR-2 agonist SLIGRL-NH2、LRGILS-NH2、LPS and LT. In the action time was 2h、14h and 24h, ELISA was used to test the concentration of IL-6 and IL-8 in supernatant of cells; SYBR Green real-time RT-PCR was used to observe expression difference of Claudin-1、Occludin and ZO-1 mRNA. The data shown that Non-activated IECs produced negligible amounts of IL-6 and IL-8. Incubation of IECs with a PAR-2 agonist resulted in a low, but significant increase in IL-6 and IL-8 expression compared with controls. To examine the possible synergy between PAR-2 agonists and LPS+LT on IEC activation, IECs were incubated with trypsin and SLIGKV-NH2 in the presence concentrations of LPS+LT Incubation of IECs with the PAR-2 agonists in the presence of LPS+LT resulted in marked potentiation of IL-6 and IL-8 production at all concentrations tested. The change in IL-8 expression was more pronounced to that of IL-6. In the PAR-2 agonist stimulation 24h, the expression of Claudin-1、Occludin and ZO-1 mRNA was significantly lower than the group of control、soybean protease inhibitor and LRGILS-NH2, the difference was significant(P<0.05) which Claudin-1 change was evident.
Above results suggested that PAR-2 had a negative regulation role on gasrointestinal mucosal barrier, and had a certain medium in the pathogenesis of diarrhea in weaned piglets. PAR-2 can promote the production of inflammatory cytokines after activation. The high wxpression of inglammatory factors can make neutrophils、eosinophils and other inflammatory cell migration to mediate inflammation in the gastrointestinal tract. Changes in the concentration of inflammatory cytokines can make the of expression decreased and shift of the three TJ proteins of Claudin-1、Occludin and ZO-1, resulting in structural damage of TJ and influenced the barrier function of epithelial cell.
引文
1.崔静,刘占举,唐芙爱.炎症性肠病患者血清肿瘤坏死因子和白介素8检测.郑州大学学报(医学版),2006,41(5)：285-287
2.程君涛,肖光夏,夏培元,等.腹内高压对兔肠道通透性及内毒素细菌移位的影响.中华烧伤杂志,2003,19(4)：229-232
3.陈载融,孙春洪.活检胃黏膜组织中氨基己糖的测定.实用医学杂志,2003,10(11)：1238
4.杜念兴.兽医免疫学.北京：中国农业出版社,2001,66-73
5.杜勇,施诚仁,张文竹,等.先天性巨结肠肠粘膜紧密连接蛋白分布表达方式的研究.临床儿科杂志,2006,24(5)：410.
6.黄国栋,李家邦,戴幸平,等.健胃愈疡颗粒对胃溃疡大鼠胃黏膜氨基己糖及磷脂含量的实验研究.中国中医急诊,2007,16(3)：327-329
7.胡泉舟,侯永清,丁斌鹰,等.α-酮戊二酸对仔猪小肠组织学形态与功能的影响.动物营养学报,2008,20(6)：662-667
8.胡心红,周红,王婷.蛋白酶激活受体1和2在结肠癌细胞的表达及其作用初探.苏大学学报(医学版),2007,17：23-27
9.侯永清,周毓平,计成,等.仔猪断奶后腹泻病因分析.饲料博览,2001,1：36-37
10.胡艳欣,佘锐萍,张洪玉,等.热应激后猪血清中IL-2、IFN-7及TNF-α水平的动态变化.畜牧兽医学报,2006,37(5)：496-499
11.陆承平.兽医微生物学.北京：中国农业出版社,2001,213-223
12.刘海军,许国铭,李兆申.氨基己糖和磷脂含量评价胃粘膜防御机制.新消化病学杂志,1997,5(7)：427-428
13.李开学,邓联民,陈碧玲,等.褪黑素对大鼠应激性溃疡保护作用研究.中国误诊学杂志,2005,5(7)：1219-1221
14.刘明江,宁宇虹.早期隔离断奶的优势与劣势.国外畜牧科技,2000,27(3)：16-20
15.林平,黄华,梅林.细胞因子与溃疡性结肠炎.湖北民族学院学报,2003,20(4)： 28-33
16.卢亚萍,杜杰.断奶仔猪腹泻原因分析及防治.养猪,2005,12：15-16
17.马洁,戴玲,赵伟.大鼠应激性溃疡幽门区降钙素基因相关肽变化对胃内胆汁反流的影响.河北医学,2007,13(6)：637-641
18.牛青霞,何韶衡.蛋白酶激活受体-2的研究进展.生理科学进展,2003,34(4)：373-375
19.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.世界华人消化杂志,2005,13(4)：443-447
20.沈国顺,刘丽霞,刘春秀.早期断奶仔猪腹泻发生的原因及预防措施.畜牧与兽医,2001,33(6)：32-33
21.石胜军,肖能坎.蛋白酶激活受体家族与感染和免疫.国外医学.生理、病理科学与临床分册,2002,22(3)：287-298
22.王国强.早期断奶仔猪腹泻发生的原因及防制.河南农业科学,1999,6：34-36
23.吴丽芹,姜惟,顾武军.半夏泻心汤对慢性胃炎合并HP感染大鼠粘液层磷脂、氨基己糖的影响.中医药研究,2001,17(1)：40-41
24.王猛,侯永清,丁斌鹰,等.精胺对断奶仔猪生产性能和血清生化指标的影响.畜牧与兽医,2008,40(5)：29-31
25.徐秀华.内源性感染的机理与预防.中国微生态学杂志,1996,8(6)：52-54
26.徐肇敏,张志宏,陈戴融,等.幽门螺旋杆菌破坏胃粘膜屏障的研究.中华内科杂志,1995,34(9)：603-605
27.杨彩梅.谷氨酰胺和甘氨酰-谷氨酰胺对断奶仔猪小肠黏膜的影响.中国粮油学报,2006,21(4)：119-122
28.杨焕民,陈萍,吴秀芬,等.冷暴露仔猪PBMC中Hsp72与血浆TNF-α、IL-6的变化规律.中国预防兽医学报,2008,30(9)：732-736
29.阳惠湘,邹益友,张熙纯,等.幽门螺杆菌感染的十二指肠溃疡患者血清降钙素基因相关肽的测定.湖南医科大学学报,1999,24(3)273-274
30.余秀文,张勇.十二指肠溃疡患者血浆降钙素基因相关肽、内皮素含量变化.基础学研究与药学研究,2007,6(2)：85-85
31.杨晓玉,张慧云,何韶衡.蛋白酶激活受体—2与炎症性疾病的关系研究进展. 陕西医学杂志,2006,35(12)：1671-1974
32.赵龙风,李红,韩德五.肠源性内毒素血症与肝病.世界华人消化杂志,2000,4(3)：1145-1149
33.朱雄伟,施文兴,湛先保,等.大鼠腹部开放伤海水浸泡后胃黏膜氨基己糖和磷脂的变化.中国现代普通外科进展,2006,9(2)：77-79
34.张中伟,秦环龙.乳酸菌对感染肠上皮细胞通透性及紧密连接蛋白表达的影响.肠内场外营养,2007,14(4)：193-200
35.张振斌,蒋宗勇,林映才,等.早期断奶仔猪的消化生理与日粮配制.中国饲料,2000,10：4-5
36. Abraham L A, Chinni C, Jenkins A L, et al. Expression of proteinase-activated receptor-2 by osteoblasts. Bone,2000,26:7-14.
37. Al Ani B, Saifeddine M, Hollenberg M D. Detection of functional receptors for the proteinase-activated-receptor-2-activating polypeptide SLIGRL-NH2 in rat vascular and gastric smooth muscle. Can J Physiol Pharmacol,1995,73:1203-1207
38. Amieva M R, Vogelmann R, Covacci A, et al. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science,2003,300: 1430-1434
39. Anderson J M. Molecular structure of tight junctions and their role in epithelial transport. News Physiol Sci,2001,16:126-130,
40. Andreeva A Y, Krause E, Muller E C, et al. Protein kinase C regulates the phosphorylation and cellular localization of occludin. J Biol Chem,2001,276: 38480-38486
41. Asokananthan N, Graham P T, Fink J, et al. Activation of Protease-Activated Receptor (PAR)-1, PAR-2, and PAR-4 Stimulates IL-6, IL-8, and Prostaglandin E2 Release from Human Respiratory Epithelial Cells. The Journal of Immunology, 2002,168:3577-3585
42. Ballard S T, Hunter J H, Taylor A E. Regulation of Tight-Junction Permeability During Nutrient Absorption Across the Intestinal Epithelium. Annual Review of Nutrition,1995,15:35-55
43. Bar-Shavit R, Maoz M, Yongjun Y, et al. Signalling pathways induced by protease-activated receptorsand integrins in T cells. Immunology,2002,105:35-46
44. Berger P, Perng D W, Thabrew H, et al. Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells. J Appl Physiol,2001,91: 1372-1379
45. Berger P, Tunon-De-Lara J M, Savineau J P, et al. Selected contribution: tryptase-induced PAR-2-mediated Ca(2+) signaling in human airway smooth muscle cells. J Appl Physiol,2001,91:995-1003
46. Bertschinger H U, Bachmann M, Mettler C, et al. Adhesive fimbriae produced in vivo by Escherichia coli 0139:K12(B):H1 associated with enterotoxaemia in pigs. Vet. Microbiol,1990,25:267-281.
47. Bohm S K, Kong W, Bromme D, et al. Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J,1996,314: 1009-1016
48. Bono F, Schaeffer P, Herault J P. et al. Factor Xa activates endothelial cells by a receptor cascade between EPR-1 and PAR-2. Arterioscler Thromb Vasc Biol,2000, 20:E107-E112
49. Brain S D. New feelings about the role of sensory nerves in inflammation. Nat Med, 2000,6:134-135
50. Bretschneider E, Kaufmann R, Braun M, et al. Evidence for proteinase-activated receptor-2 (PAR-2)-mediated mitogenesis in coronary artery smooth muscle cells. Br J Pharmacol,1999,126:1735-1740
51. Callesen J, Halas D, Thorup F, et al. The effects of weaning age, diet composition, and categorisation of creep feed intake by piglets on diarrhoea and performance after weaning. Livestock Science,2007,108:120-123
52. Camerer E, Huang W, Coughlin S R. Tissue factor-and factor X-dependent activation of protease-activated receptor 2 by factor Ⅶa. PNAS,2000,97(10): 5255-5260
53. Carr M J, Schechter N M, Undem B J. Trypsin-induced, neurokinin-mediated contraction of guinea pig bronchus. Am J Respir Crit Care Med,2000,162: 1662-1667
54. Cederqvist K, Haglund C, Heikk ila P, et al. H igh expression of pulmonary Proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants. Pediatr Res,2005,57(6):831
55. Cenac N, Coelho A M, Nguyen C, et al. Induction of Intestinal Inflammation in Mouse by Activation of Proteinase-Activated Receptor-2. American Journal of Pathology,2002,161:1903-1915
56. Cera K R, Mahan R F, Cross R F, et al. Effect of Age, Weaning and Postweaning Diet on Small Intestinal Growth and Jejunal Morphology in Young Swine. J. Anim Sci,1988,66:574-584
57. Chandana S, Sanjay K, Nigam, et al. Expanding Role of G Proteins in Tight Junction Regulation:GaS Stimulates TJ Assembly. Biochemical and Biophysical Research Communications,2001,285(2):250-256.
58. Chi L Q, Li Y A, Stehno-bittel L, et al. Interleukin-6 Production by Endothelial Cells via Stimulation of Protease-Activated Receptors Is Amplified by Endotoxin and Tumor Necrosis Factor-a. JOURNAL OF INTERFERON AND CYTOKINE ESEARCH,2001,21:231-240
59. Chung W O, Hansen S R, Rao D, et al. Protease-activated receptor signaling increases epithelial antimicrobial peptide expression. J Immunol,2004,173: 5165-5170.
60. Cicala C, Morello S, Vellecco V, et al. Basal nitric oxide modulates vascular effects of a peptide activating protease-activated receptor 2. Cardiovascular Research,2003, 60:431-437
61. Citi S. The cytoplasmic plaque proteins of the tight junction. In:Tight Junctions (2nd ed.), edited by Anderson JM and Cereijido M. Boca Raton, FL:CRC,2001,231-264
62. Cocks T M, Sozzi V, Moffatt J D, et al. Protease-activated receptors mediate apamin-sensitive relaxation of mouse and guinea pig gastrointestinal smooth muscle. Gastroenterology,1999,116:586-92
63. Coelho A M, Vergnolle N, Guiard B, et al. Proteinases and proteinase-activated receptor 2; a possible role to promote visceral hyperalgesia.Gastroenterology,2000, 122:1035-1047
64. Collins J E, Bergeland M E, Bouley D, et al. Diarrhea associated with Clostridium perfringens type A enterotoxin in neonatal pigs. J Vet Diagn Invest,1989,1:351-353
65. Cordenonsi M, D'Atri F, Hammar E, et al. Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3 and myosin. J Cell Biol,1999,147: 1569-1581
66. D'Andrea M R, Derian C K, Leturcq D, et al. Characterization of Protease-activated Receptor-2 Immunoreactivity in Normal Human Tissues. Journal of Histochemistry and Cytochemistry,1998,46:157-164
67. D'Andrea M R, Rogahn C J, Andrade-Gordon P. Localization of protease-activated receptors-1 and-2 in human mast cells:indications for an amplified mast cell degranulation cascade. Biotech Histochem,2000,75:85-90
68. Damiano B P, Cheung W M, Santulli R J, et al. Cardiovascular Responses Mediated by Protease-Activated Receptor-2 (PAR-2) and Thrombin Receptor (PAR-1) are Distinguished in Mice Deficient in PAR-2 or PAR-1. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,1999,288(2): 671-678
69. David C, Morrison, John L, et al. Endotoxins and disease mechanisms. Annual Review of Medicine,1987,38:417-432
70. Dean P, Kenny B. Intestinal barrier dysfunction by enteropathogenic Eseherichia coli is mediated by two effector molecuhs and a bacterial surface protein. Mol Microbiol, 2004,54(3):665-675
71. Derian C K, Eckardt A J, Andrade-Gordon P. Differential regulation of human keratinocyte growth and differentiation by a novel family of protease-activated receptors. Cell Growth Differ,1997,8:743-749
72. Dery O, Corvera C U, Steinhoff M, et al. Proteinase-activated receptors:novel mechanisms of signaling by serine proteases. American Journal of Physiology,1998, 274:1429-1452.
73. Ebnet K, Suzuki A, Ohno S, et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J,2001,14:3738-3748
74. Egesten A, Calafat J, Knol E F, et al. Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes. Blood,1996,87(9): 3910-3918
75. Evans D G, Evans D J, Tjoa W. Hemagglutination of human Group A erythrocytes by enterotoxigenic E. coli isolated from adults with diarrhea:correlation with colonization factor. Infect. Immun,1977,18:330-337
76. Eveline E, Schneeberger, Lynch R D. The tight junction:a multifunctional complex. Am J Physiol Cell Physiol,2004,286:C1213-C1228
77. Fasano A, Fiorentini C, Donelli G, et al. Zonula occludens toxin modulates tight junctions through p rotein kinase C-dependent actin reorganization in vitro. J Clin Invest,1995,96(6):710-720
78. Ferrell W R, Lockhart J C, Kelso E B, et al. Essential role for proteinaseactivated receptor-2 in arthritis. J Clin Invest,2003,111:35-41
79. Fiorucci S, Mencarelli A, Palazzetti B, et al. Proteinase-activated receptor 2 is an anti-inflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis. National Acad Sciences,2001,98(24):13936-13941
80. Francois Madec, Nathalie Bridoux, SteAphane Bounaix, et al. Experimental models of porcine post-weaning colibacillosis and their relationship to post-weaning diarrhoea and digestive disorders as encountered in the filed. Veterinary Microbiology,2000,72:295-310
81. Furuse M, Hirase T, Ltoh M, et al. Occludin:a novel integral membrane protein localizing at tight junctions, JCB vol,1993,123(6):1777-1788
82. Furuse M, Sasaki H, Fujimoto K, et al. A single gene product, claudin-1 or-2, reconstitutes tight junction strands and recruits occludin in fibroblasts. J Cell Biol, 1998,143:391-401
83. Gao C, Liu S, Hu H Z, et al. Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine. Gastroenterology,2002, 123:1554-1564
84. Garabal J I, Gonzalez E A, Vazquez F, et al. Serogroups of E. coli isolated from piglets in Spain. Vet. Microbiol,1996,48:113-123
85. Gerhard Rogler M D, Tilo Andus M D. Cytokines in Inflammatory Bowel Disease.world journal of surgery,1998,22:382-389
86. Giulia R, Iolanda M, Isabella V, et al. The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco22 cell line. J Nutr Biochem,2002,13(3):157-167
87. Gottardi C J, Arpin M, Fanning A S, et al. The junctionassociated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts, Proc Natl Acad Sci USA,1996,93:10779-10784
88. Green B T, Bunnett N W, Kulkarni-Narla A, et al. Intestinal type 2 proteinase-activated receptors:expression in opioid-sensitive secretomotor neural circuits that mediate epithelial ion transport. J Pharmacol Exp Ther,2000,295: 410-416
89. Gregouy M, Deitch. Role of the gut in multiple organ failure:bacterial translocation and permeability changes. World Journal of Surgery,1996,20:411-417
90. Griffin CT, Srinivasan Y, Zheng Y W, et al. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science,2001,293:1666-1670
91. Haller D, Jobin C. Interaction between resident luminal bacteria and the host:can a healthy relationship turn sour? J Pediatr Gastroenterol Nutr,2004,38:123-136
92. Hampson D J. Alterations in piglet small intestinal structure at weaning. Res.Vet.Sci, 1986,40(1):32-40
93. Han X, Fink M P, Delude R L. Proinflammatory cytokines causeNO-dependent and-independent changes in exp ression and localization of tight junction p roteins in intestinal ep ithelial cells. Shock,2003,19(3):229-237
94. Harmsen M M, van Solt C B, Hoogendoorn A, et al. Escherichia coli F4 fimbriae specific llama single-domain antibody fragments effectively inhibit bacterial adhesion in vitro but poorly protect against diarrhoea. Veterinary Microbiology, 2005,111:89-98
95. He S, Aslam A, Gaca M D, et al. Inhibitors of tryptase as mast cell-stabilizing agents in the human airways:effects of tryptase and other agonists of proteinase-activated receptor 2 on histamine release. J Pharmacol Exp Ther,2004,309(1):119-126
96. Hirano K, Kanaide H. Role of Protease-activated Receptors in the Vascular System. Journal of Atheroclwrosis and Thrombosis,2003,10(4):211-225
97. Hirase T, Staddon J M, Saitou M, et al. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci,1997,110:1603-1613
98. Hirota Y, Osuga Y, Hirata T, et al. Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells. Human Reproduction,2005,20(12):3547-3553
99. Hoevel T, Macek R, Mundigl O, et al. Expression and targeting of the tight junction protein CLDN1 in CLDN1-negative human breast tumor cells. Journal of Cellular Physiology,2002,191(1):60-68
100.Hollenberg M, Compton S J. International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors. PHARMACOLOGICAL REVIEWS,2002,54(2): 203-217
101.Hoogerwerf W A, Zou L, Shenoy M, et al. The proteinase-activated receptor2 is involved in nociception. J Neurosci,2001,21:9036-9042
102.Horiuchi T, Weller P F. Expression of vascular endothelial growth factor by human eosinophils:upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5. Am J Respir cell Mol Biol,1997,17(1):70-77
103.Hou L, Kapas S, Cruchley A T, et al. Immunolocalization of proteaseactivated receptor-2 in skin:receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology,1998,94:356-362
104.Howells G L, Macey M G, Chinni C, et al. Proteinase-activated receptor-2: expression by human neutrophils. J Cell Sci,1997,110:881-887
105.Hwa J J, Ghibaudi L, Williams P, et al. Evidence for the presence of a proteinase activated receptor distinct from the thrombin receptor in vascular endothelial cells. Circ Res,1996,78:581-588
106.Imberechts H, De Greve H, Linterman P. The pathogenesis of edema disease in swine. Vet. Microbiol,1992,31:221-233
107.1osub R, Klug J, Fijak M, et al. Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2. J Pathol,2006,208:686-98
108.Jacob C, Cottrell G S, Gehringer D, et al. c-Cb1 Mediates Ubiquitination, Degradation, and Down-regulation of Human Protease-activated Receptor 2. The Journal of Biological Chemistry,2005,280:16076-16087
109.Junghyun Kim, Changsun Choi, Chanhee Chae. Prevalence of eaeA+Escherichia coli isolated from pigs with diarrhea. J Vet Diagn Invest,2001,13:355-356
110.Kahn M L, Zheng Y W, Huang W, et al. A dual thrombin receptor system for platelet activation. Narure,1998,394:690-694
111.Kanke T, Scott R, Macfarlane, et al. Proteinase-activated Receptor-2-mediated Activation of Stress-activated Protein Kinases and Inhibitory kB Kinases in NCTC 2544 Keratinocytes. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2001, 276(34):31657-31666
112.Kawabata A, Kinoshita M, Nishikawa H, et al. The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection. J.Clin.Invest, 2001,107(11):1443-1450
113.Kawabata A, Kuroda R, Nishida M, et al. Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland:Immunolocalization and involvement of nitric oxide in the evoked amylase secretion. Life sciences,2002,71(20):2435-2446
114.Kawabata A, Morimoto N, Nishikawa H, et al. Activation of Protease-Activated Receptor-2 (PAR-2) Triggers Mucin Secretion in the Rat Sublingual Gland. Biochemical and Biophysical Research Communications,2000,270(1): 298-302
115.Kawabata A, Saifeddine M, Al-Ani B, et al. Evaluation of proteinase-activated receptor-1 (PAR1)agonists and antagonists using a cultured cell receptor desensitization assay:activation of PAR2 by PAR1 targeted ligands. Journal of Pharmacology and Experimental Therapeutics,1999,288:358-70.
116.Kawao N, Sakaguchi Y, Tagome A, et al. Protease-activated receptor-2 (PAR-2) in the rat gastric mucosa:immunolocalization and facilitation of pepsin/pepsinogen secretion. Br J Pharmacol,2002,135(5):1292-1296
117.Kim J A, Choi S C, Yun K J, et al. Expression of protease-activated receptor 2 in ulcerative colitis. Inflammatory Bowel Diseases,2006,9(4):224-229
118.Komuro T, Miwa S, Minowa T, et al. The involvement of a novel mechanism distinct from the thrombin receptor in the vasocontraction induced by trypsin. Br J Pharmacol,1997,120:851-856
119.Kong W, McConalogue K, Khitin L M, et al. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci USA,1997, 94:8884-8889
120.Koo B H, Chung K H, Hwang K C, et al. Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2. FEBS Lett,2002,523:85-89
121.LanRS, Knight D A, Stewart G A, et al. Role of PGE(2) in protease-activated receptor-1,-2 and-4 mediated relaxation inthe mouse isolated trachea. Br J Pharmacol,2001,132:93-100
122.Levine M M. Escherichia Coli that cause diarrhea:enterotoxigenic,enteropa thogenic,enteroinvasive, enterohemorrhaic and enteroadherent. J.Int:Dis,1987,155: 377-389
123.Lichtenberger L M, Graziani L A, Dial E J, et al. Role of surface-active phospholipids in gastric cytoprotection. Science,1983,219(4590):1327-1329
124.Lindner J R, Kahn M L, Coughlin S R, et al. Delayed onset of inflammation in protease-activated receptor-2-deficientmice. J Immunol,2000,165:6504-6510
125.Lourbakos A, Chinni C, Thompson P, et al. Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis. FEBS Lett,1998,435:45-48
126.Lourbarkos A, Potemba J, Travis J, et al. Arginine-specific proteinase from Porphyromonas gingivalis activates proteinase-activated receptors on human oral epithelial cells and induces interlukin-6 secretion. Infect Immun,2001,69: 5121-5130.
127.Luk G D, Bayless T M, Baylin S B. Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity. J Clin Invest,1980,66(1): 66-70
128.Luk G D, Bbyleg T M, Bbylin S B. Plasma postheparin diamine oxidase sensitive p rovocative test for quantitating length of acute intestinal mucosal injury in the rat. J. clinical investigation,1983,71(5):1305-1308
129.Macfarlane S R, Seatter M J, Kanke T, et al. Proteinase-activated receptors. Pharmacol Rev,2001,53:245-282
130.Madara J L. ntestinal absorptive cell tight junctions are linked to cytoskeleton. Am J Physiol Cell Physiol,1987,253:C171-C175
131.Mahan D C, Lepine A J. Effect of pig weaning weight and associated feeding programs on subsequent performance to 105 kilograms body weight. J.Anim.Sci, 1991,69:1370-1378
132.Mainuos M R, Deitch E A, Block E F, et al. Baeterial translocation and potential role in the pathogenesis of multiple organ failure. J Intentive Care Med,1992,7: 101
133.Manela F D, Ren J, Gao J, et al. Calcitionin gene-related peptide modulates acid-regulation of somatostatatin and gastrin release from rat autrum. Gastroenterology,1995,109(3):701-706
134.Mankertz J, Tavalali S, Schmitz H, et al. Expression from the human occluding promoter is affected by tumor necrosis factor and interferon. J Cell Sci,2000,113: 2085-2090
135.Mari B, Guerin S, Far D F, et al. Thrombin and trypsin-induced Ca2+ mobilization in human T cell lines through interaction with different protease-activated receptors. FASEB J,1996,10:309-316
136.Mc Crachen B A, Spurlock M E, Roos M A, et al. Weaning anorexia may contribute to local in flammation in the piglet small intestine. Journal of Nutrition,1999,129: 613-619
137.Mclean P G, Aston D, Sarkar D, et al. Protease-activated receptor-2 activation causes EDHF-like coronary vasodilation:selective preservation in ischemia/reperfusion injury:involvement of lipoxygenase products, VR1 receptors, and C-fibers. Cirec Res,2002,90(4):465-472
138.Moffatt J D, Jeffrey K L, Cocks T M.Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice. Am J Respir Cell Mol Biol, 2002,26:680-684
139.Miike S, Me William A S, Kita H. Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2. J Immunol,2001,167:6615-6622
140.Mirza H, Yatsula V, Bahou W F. The proteinase activated receptor-2 (PAR-2) mediates mitogenic responses in human vascular endothelial cells. J Clin Inves, 1996,97:1705-1714
141.Montalto M, Cuoco L, Ricci R, et al. Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease. Digestion, 2002,65 (4):227.
142.Morencos F C, Castano GDLH, Romas L M, et al. Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci,1996,41:552-556
143.Morrow C M K, Mruk D, Cheng C Y, et al. Claudin and occludin expression and function in the seminiferous epithelium. Phil Trans R Soc,2010,365:1679-1696
144.Mozsik G, Szolcsanyi J, Domotor A. Capsaicin research as a new tool to approach of the human gastrointestinal physiology, pathology and pharmacology. Inflammopharmacology,2008,15(6):232-245
145.Muza-Moons M M, Schneeberger E E, Hecht G A. Enteropathogenic Eschefichia coli infection leads to appearance of aberrant tight iunctions strands in the lateral membrane of intestinal eplthelial cells. Cell Microbiol,2004,6(8):783-93
146.Nagy B, Casey T A, Moon H W. henotype and genotype of E. coli isolated from pigs with ostweaning diarrhea in Hungary. J. Clin. Microbiol,1990,28: 651-653
147.Nasdala I, Wolburg-Buchholz K, Wolburg H, et al. A Transmembrane Tight Junction Protein Selectively Expressed on Endothelial Cells and Platelets. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2002,277(18):16294-16303
148.Nguyen T D, Moody M W, Steinhoff M, et al. Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2. J Clin Invest, 1999,103:261-269
149.Nishibori M, Mori S, Takahashi H K. Physiology and pathohysiology of proteinase activated receptors (PARs):PAR2 mediated proliferation of colon cancer cell. Pharmacol Sci,2005,97:25-30
150.Nishikawa H, Kawabata A, Kuroda R, et al. Characterization of protease-activated receptors in rat peritoneal mast cells. Jpn J Pharmacol,2000,82:74-77
151.Nysted S, Emilsson K, Wahlested C, et al. Molecular clonin of a potential proteinase activated receptor. Proc Natl Acad Sci USA,1994,91:9208-9212
152.Nystedt S, Ramakrishnan V, Sundelin J. The proteinaseactivated receptor 2 is induced by inflammatory mediators in human endothelial cells. Comparison with the thrombin receptor. J Biol Chem,996,271:14910-14915
153.Ohno T, Hattori Y, Komine R, et al. Roles of calcitonin gene related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis. Gastroenterology,2008,134(1):215-225
154.Okamoto T, Nishibori M, Sawada K, et al. The effects of stimulating protease-activated receptor-1 and-2 in A172 human glioblastoma. J Neural Transm, 2001,108:125-140
155.Osek J. Prevalence of virulence factors of Escherichia coli strains isolated from diarrheic and healthy piglets after weaning. Veterinary Microbiology,1999,68: 209-217
156.Ossovskaya V S, Bunnet N W. Protease-activated receptors:contribution to physiology and disease. Physiol Rev,2004,84:579-621
157.Patel R T, Deen K I, Youngs D, et al. Interleukin 6 is a prognostic indicator of outcome in severe intra—abdominal sepsis. Br J Surg,1994,81 (9):1036-1038
158.Patel S K, Dotson J, Allen K P, et al.Identification and molecular charaterization of EatA,an autotransporter protein of enterotoxigenic Escherichia coli.Infect Imumun, 2004,72(3):1786-1794.
159.Pizzuti D, Bortolami M, Mazzon E, et al.Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten free diet. Dig Liver Dis,2004,36 (5):337
160.Ricciardolo F L, Steinhoff M, Amadesi S, et al. Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways. AmJ Respir Crit Care Med, 2000,161:1672-1680
161.Powell D W. Barrier function of ep ithelia. Am J Physiol Legacy Content,1981, 241(4):G2752288.
162.Robert H R. Inflammatory bowel disease Differential diagnosis and cancer of the small and large bowel. Digestive Diseases and Sciences,1985,30(12):1573-2568
163.Rolfe R D. The role of probiotic cultures in the control of gastrointestinal health. J Nutr,2000,130:396-402
164.Rosenfeld M G, Mermod J J, Amara S G, et al. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing.Nature,1983, 304:129-315
165.Saifeddine M, Al-Ani B, Cheng C H, et al. Rat proteinase-activated receptor-2 (PAR-2):cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. British Journal of Pharmacology,1996,118:521-30
166.Sakakibara A, Furuse M, Saitou M, et al. Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol,1997,137:1393-1401
167.Sato K, Ninomiya H, Ohkura S, et al. Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation. Br J Pharmacol, 2006,148(2):200-207
168.Schmidlin F, Amadesi S, Dabbagh K, et al. Proteaseactivated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol,2002,169:5315-5321
169.Schmidlin F, Amadesi S, Vidil R, et al. Expression and Function of Proteinase-activated Receptor 2 in Human Bronchial Smooth Muscle. Am. J. Respir. Crit.Care Med.,2001,164(7):1276-1281
170.Schneeberger E E, Lynch R D. The tight junction:a multifunctional complex. Am J Physiol Cell Physiol,2004,286(6):1213-1228.
171.Schultheiss M, Neumcke B, Richter H P. Endogenous trypsin receptors in Xenopus oocytes:linkage to internal calcium stores. Cell Mol Life Sci,1997,53:842-849
172.Scudamore C L, Jepson M A, Hirst B H, et al. The rat mucosal mast cell chymase, RMCP-Ⅱ, alters epithelial cell monolayer permeability in association with altered distribution of the tight junction proteins ZO-1 and occludin. Eur J Cell Biol,1998, 75(4):321
173.Sekiguchi F, Kawabata A. Protease-Activated Receptors (PARs) as Therapeutic Targets:Development of Agonists/Antagonists and Modulation of Gastrointestinal Functions. Drug Design Reviews-online,2004,1(4):287-294
174.Shifflett D E, Clayburgh D R, Koutsouris A, et al. Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo. Lab Invest,2005,85(10): 1304-1324
175.Shobha G, Narayan Raman, Simon J. Atkinson Rho GTPase signaling regulates tight junction assembly and p rotects tight junctions during ATP dep letion. Am J Physiol Cell Physiol,1999,275(3):C798-C809
176.Shpacovitch V M, Brzoska T, Bunnett N W, et al. Agonists of protease-activated receptor-2 induce cytokine release and upregulation of cell adhesion molecules in human dermal microvascular endothelial cells. J Invest Dermatol,2001,117:458-467
177.Smith R, Ransjo M, Tatarczuch L, et al. Activation of proteinase-activated receptor-2 leads to inhibition of osteoclast differentiation. J Bone Miner Res,2004,19:507-516.
178.Snoeck V, Huyghebaert N, Cox E, et al. Enteric-coated pellets of F4 fimbriae for oral vaccination of suckling piglets against enterotoxigenic Escherichia coli infections. Veterinary Immunology and Immunopathology,2003,96:219-227
179.Stanislaw J K. Gastric Cytoprotection. Scandinavian Journal of Gastroenterology, 1985,20(5):543-553
180.Steinhoff M, Buddenkotte J, Shpacovitch V, et al. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev,2005,26:1-43
181.Stenton G R, Nohara O, De'ry R E, et al. Proteinase-activated receptor (PAR)-1 and-2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 andPAR-2. J Pharmacol Exp Ther,2002,302:466-474
182.Storck J, Kusters B, Vahland M, et al. Trypsin induced von Willebrand factor release from human endothelial cells in mediated by P AR-2 activation. Thromb Res,1996, 84:463-473
183.Swisshelm K, Machl A, Planitzer S, et al. SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene,1999/226(2):285-295
184.Syeda F, Grosjean J, Rebecca A, et al. Cyclooxygenase-2 Induction and Prostacyclin Release by Protease-activated Receptors in Endothelial Cells Require Cooperation between Mitogen-activated Protein Kinase and NF-KB Pathways. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2006,281(17):11792-11804
185.Takagi K, Nakao M, Ogura Y, et al. Sensitive colorimetric assay of serum diamine oxidase. Clinica Chimica Acta,1994,226(1):67-75
186.Takaishi K, Sasaki T, Korani H, et al. Regulation of cell-cel adhesion by Rac and Rho small G proteins in MDCK cells. J Cell Biol,1997,139(8):1047-1059
187.Temkin V, Kantor B, Weg V, et al. Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release. J Immunol,2002,169:2662-2669
188.Tina R D, Nicholas J L, Karen L H, et al. Interleukin-6 Causes Endothelial Barrier Dysfunction via the Protein Kinase C Pathway. the Annual Meeting of the Association for Academic Surgery,2001:15-17
189.Thomas A C, Cheryl J H, Robert A S, et al. Expression of Heat-Stable Enterotoxin STb by Adherent Escherichia coli Is Not Sufficient To Cause Severe Diarrhea in Neonatal Pigs. INFECTION AND IMMUNITY,1998,66(3):1270-1272
190.Tobias N M, Catherine S, Bradley M D. Zonula occludens-1 is a scaffolding protein for signalingmolecules. J Biol Chem,2002,277(28):24855-24858
191.Tobias N M, Jennifer H, Catherine S, et al. Gα12 regulates ep ithelial cell junctions through Src tyrosine kinases. Am J Physiol Cell Physiol,2003,285 (5): C1281-C1293
192.Vergnolle N, Ferazzini M, Buddenkotte J, et al. Proteinase-activated receptors:novel signals for peripheral nerves. TRENDS in Neurosciences,2003,26(9):496-500
193.Vergnolle N. Proteinase-activated receptor-2-activating peptides induce leukocyte rolling, adhesion, and extravasation in vivo. J Immunol,1999,163:5064-5069
194.Victor T, Du toit R, Van Zyl J, et al. Improved Method for the Routine Identification of Toxigenic Escherichia coli by DNA Amplification of a Conserved Region of the Heat-Labile Toxin A Subunit. JOURNAL OF CLINICAL MICROBIOLOGY,1991, 29(1):158-161
195.Vliagoftis H, Schwingshackl A, Miline C D, et al. Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cell. J Allergy Clin Immunol,2000,106(3):537-545
196.Vouret-Craviari V, Grall D, Van Obberghen-Schilling E. Modulation of rho GTPase activity in endothelial cells by selective proteinase-activated receptor (PAR) agonists. J Thromb Haemost,2003,1:1103-1111
197.VuTK, Hung D T, Wheaton V I, et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell,1991, 64(6):1057-1068
198.Wang Z, Wade P, Mandell K J, et al. Raf-1 represses expression of the tight junction protein occluding via activation of the zinc-finger transcription factor slug. Oncogene,2006,25(1):1-9
199.Wang Z, Wade P, Mandell K J, et al. The second loop of occludin is required for suppression of Rafl-induced tumor growth. Oncogene,2005,24(27):4412-4420
200.Wellock I J, Fortomaris P D, Houdijk J G M, et al. Effect of weaning age, protein nutrition and enterotoxigenic Escherichia coli challenge on the health of newly weaned piglets. Livestock Science,2007,108:102-105
201.Wittig W, Klie H, Gallien P, et al. Prevalence of the fimbrial antigens F18 and K88 enterotoxins and verotoxins among E. coli isolated from weaned pigs. Zbl. Bakt, 1995,283:95-104.
202.Wong V, Gumbiner B M. A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J Cell Biol,1997, 136:399-409
203.Youakim A, Ahdieh M. Interferon-gamma decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin. Am J Physiol,1999,276:1279
2.程君涛,肖光夏,夏培元,等.腹内高压对兔肠道通透性及内毒素细菌移位的影响.中华烧伤杂志,2003,19(4)：229-232
3.陈载融,孙春洪.活检胃黏膜组织中氨基己糖的测定.实用医学杂志,2003,10(11)：1238
4.杜念兴.兽医免疫学.北京：中国农业出版社,2001,66-73
5.杜勇,施诚仁,张文竹,等.先天性巨结肠肠粘膜紧密连接蛋白分布表达方式的研究.临床儿科杂志,2006,24(5)：410.
6.黄国栋,李家邦,戴幸平,等.健胃愈疡颗粒对胃溃疡大鼠胃黏膜氨基己糖及磷脂含量的实验研究.中国中医急诊,2007,16(3)：327-329
7.胡泉舟,侯永清,丁斌鹰,等.α-酮戊二酸对仔猪小肠组织学形态与功能的影响.动物营养学报,2008,20(6)：662-667
8.胡心红,周红,王婷.蛋白酶激活受体1和2在结肠癌细胞的表达及其作用初探.苏大学学报(医学版),2007,17：23-27
9.侯永清,周毓平,计成,等.仔猪断奶后腹泻病因分析.饲料博览,2001,1：36-37
10.胡艳欣,佘锐萍,张洪玉,等.热应激后猪血清中IL-2、IFN-7及TNF-α水平的动态变化.畜牧兽医学报,2006,37(5)：496-499
11.陆承平.兽医微生物学.北京：中国农业出版社,2001,213-223
12.刘海军,许国铭,李兆申.氨基己糖和磷脂含量评价胃粘膜防御机制.新消化病学杂志,1997,5(7)：427-428
13.李开学,邓联民,陈碧玲,等.褪黑素对大鼠应激性溃疡保护作用研究.中国误诊学杂志,2005,5(7)：1219-1221
14.刘明江,宁宇虹.早期隔离断奶的优势与劣势.国外畜牧科技,2000,27(3)：16-20
15.林平,黄华,梅林.细胞因子与溃疡性结肠炎.湖北民族学院学报,2003,20(4)： 28-33
16.卢亚萍,杜杰.断奶仔猪腹泻原因分析及防治.养猪,2005,12：15-16
17.马洁,戴玲,赵伟.大鼠应激性溃疡幽门区降钙素基因相关肽变化对胃内胆汁反流的影响.河北医学,2007,13(6)：637-641
18.牛青霞,何韶衡.蛋白酶激活受体-2的研究进展.生理科学进展,2003,34(4)：373-375
19.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.世界华人消化杂志,2005,13(4)：443-447
20.沈国顺,刘丽霞,刘春秀.早期断奶仔猪腹泻发生的原因及预防措施.畜牧与兽医,2001,33(6)：32-33
21.石胜军,肖能坎.蛋白酶激活受体家族与感染和免疫.国外医学.生理、病理科学与临床分册,2002,22(3)：287-298
22.王国强.早期断奶仔猪腹泻发生的原因及防制.河南农业科学,1999,6：34-36
23.吴丽芹,姜惟,顾武军.半夏泻心汤对慢性胃炎合并HP感染大鼠粘液层磷脂、氨基己糖的影响.中医药研究,2001,17(1)：40-41
24.王猛,侯永清,丁斌鹰,等.精胺对断奶仔猪生产性能和血清生化指标的影响.畜牧与兽医,2008,40(5)：29-31
25.徐秀华.内源性感染的机理与预防.中国微生态学杂志,1996,8(6)：52-54
26.徐肇敏,张志宏,陈戴融,等.幽门螺旋杆菌破坏胃粘膜屏障的研究.中华内科杂志,1995,34(9)：603-605
27.杨彩梅.谷氨酰胺和甘氨酰-谷氨酰胺对断奶仔猪小肠黏膜的影响.中国粮油学报,2006,21(4)：119-122
28.杨焕民,陈萍,吴秀芬,等.冷暴露仔猪PBMC中Hsp72与血浆TNF-α、IL-6的变化规律.中国预防兽医学报,2008,30(9)：732-736
29.阳惠湘,邹益友,张熙纯,等.幽门螺杆菌感染的十二指肠溃疡患者血清降钙素基因相关肽的测定.湖南医科大学学报,1999,24(3)273-274
30.余秀文,张勇.十二指肠溃疡患者血浆降钙素基因相关肽、内皮素含量变化.基础学研究与药学研究,2007,6(2)：85-85
31.杨晓玉,张慧云,何韶衡.蛋白酶激活受体—2与炎症性疾病的关系研究进展. 陕西医学杂志,2006,35(12)：1671-1974
32.赵龙风,李红,韩德五.肠源性内毒素血症与肝病.世界华人消化杂志,2000,4(3)：1145-1149
33.朱雄伟,施文兴,湛先保,等.大鼠腹部开放伤海水浸泡后胃黏膜氨基己糖和磷脂的变化.中国现代普通外科进展,2006,9(2)：77-79
34.张中伟,秦环龙.乳酸菌对感染肠上皮细胞通透性及紧密连接蛋白表达的影响.肠内场外营养,2007,14(4)：193-200
35.张振斌,蒋宗勇,林映才,等.早期断奶仔猪的消化生理与日粮配制.中国饲料,2000,10：4-5
36. Abraham L A, Chinni C, Jenkins A L, et al. Expression of proteinase-activated receptor-2 by osteoblasts. Bone,2000,26:7-14.
37. Al Ani B, Saifeddine M, Hollenberg M D. Detection of functional receptors for the proteinase-activated-receptor-2-activating polypeptide SLIGRL-NH2 in rat vascular and gastric smooth muscle. Can J Physiol Pharmacol,1995,73:1203-1207
38. Amieva M R, Vogelmann R, Covacci A, et al. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. Science,2003,300: 1430-1434
39. Anderson J M. Molecular structure of tight junctions and their role in epithelial transport. News Physiol Sci,2001,16:126-130,
40. Andreeva A Y, Krause E, Muller E C, et al. Protein kinase C regulates the phosphorylation and cellular localization of occludin. J Biol Chem,2001,276: 38480-38486
41. Asokananthan N, Graham P T, Fink J, et al. Activation of Protease-Activated Receptor (PAR)-1, PAR-2, and PAR-4 Stimulates IL-6, IL-8, and Prostaglandin E2 Release from Human Respiratory Epithelial Cells. The Journal of Immunology, 2002,168:3577-3585
42. Ballard S T, Hunter J H, Taylor A E. Regulation of Tight-Junction Permeability During Nutrient Absorption Across the Intestinal Epithelium. Annual Review of Nutrition,1995,15:35-55
43. Bar-Shavit R, Maoz M, Yongjun Y, et al. Signalling pathways induced by protease-activated receptorsand integrins in T cells. Immunology,2002,105:35-46
44. Berger P, Perng D W, Thabrew H, et al. Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells. J Appl Physiol,2001,91: 1372-1379
45. Berger P, Tunon-De-Lara J M, Savineau J P, et al. Selected contribution: tryptase-induced PAR-2-mediated Ca(2+) signaling in human airway smooth muscle cells. J Appl Physiol,2001,91:995-1003
46. Bertschinger H U, Bachmann M, Mettler C, et al. Adhesive fimbriae produced in vivo by Escherichia coli 0139:K12(B):H1 associated with enterotoxaemia in pigs. Vet. Microbiol,1990,25:267-281.
47. Bohm S K, Kong W, Bromme D, et al. Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J,1996,314: 1009-1016
48. Bono F, Schaeffer P, Herault J P. et al. Factor Xa activates endothelial cells by a receptor cascade between EPR-1 and PAR-2. Arterioscler Thromb Vasc Biol,2000, 20:E107-E112
49. Brain S D. New feelings about the role of sensory nerves in inflammation. Nat Med, 2000,6:134-135
50. Bretschneider E, Kaufmann R, Braun M, et al. Evidence for proteinase-activated receptor-2 (PAR-2)-mediated mitogenesis in coronary artery smooth muscle cells. Br J Pharmacol,1999,126:1735-1740
51. Callesen J, Halas D, Thorup F, et al. The effects of weaning age, diet composition, and categorisation of creep feed intake by piglets on diarrhoea and performance after weaning. Livestock Science,2007,108:120-123
52. Camerer E, Huang W, Coughlin S R. Tissue factor-and factor X-dependent activation of protease-activated receptor 2 by factor Ⅶa. PNAS,2000,97(10): 5255-5260
53. Carr M J, Schechter N M, Undem B J. Trypsin-induced, neurokinin-mediated contraction of guinea pig bronchus. Am J Respir Crit Care Med,2000,162: 1662-1667
54. Cederqvist K, Haglund C, Heikk ila P, et al. H igh expression of pulmonary Proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants. Pediatr Res,2005,57(6):831
55. Cenac N, Coelho A M, Nguyen C, et al. Induction of Intestinal Inflammation in Mouse by Activation of Proteinase-Activated Receptor-2. American Journal of Pathology,2002,161:1903-1915
56. Cera K R, Mahan R F, Cross R F, et al. Effect of Age, Weaning and Postweaning Diet on Small Intestinal Growth and Jejunal Morphology in Young Swine. J. Anim Sci,1988,66:574-584
57. Chandana S, Sanjay K, Nigam, et al. Expanding Role of G Proteins in Tight Junction Regulation:GaS Stimulates TJ Assembly. Biochemical and Biophysical Research Communications,2001,285(2):250-256.
58. Chi L Q, Li Y A, Stehno-bittel L, et al. Interleukin-6 Production by Endothelial Cells via Stimulation of Protease-Activated Receptors Is Amplified by Endotoxin and Tumor Necrosis Factor-a. JOURNAL OF INTERFERON AND CYTOKINE ESEARCH,2001,21:231-240
59. Chung W O, Hansen S R, Rao D, et al. Protease-activated receptor signaling increases epithelial antimicrobial peptide expression. J Immunol,2004,173: 5165-5170.
60. Cicala C, Morello S, Vellecco V, et al. Basal nitric oxide modulates vascular effects of a peptide activating protease-activated receptor 2. Cardiovascular Research,2003, 60:431-437
61. Citi S. The cytoplasmic plaque proteins of the tight junction. In:Tight Junctions (2nd ed.), edited by Anderson JM and Cereijido M. Boca Raton, FL:CRC,2001,231-264
62. Cocks T M, Sozzi V, Moffatt J D, et al. Protease-activated receptors mediate apamin-sensitive relaxation of mouse and guinea pig gastrointestinal smooth muscle. Gastroenterology,1999,116:586-92
63. Coelho A M, Vergnolle N, Guiard B, et al. Proteinases and proteinase-activated receptor 2; a possible role to promote visceral hyperalgesia.Gastroenterology,2000, 122:1035-1047
64. Collins J E, Bergeland M E, Bouley D, et al. Diarrhea associated with Clostridium perfringens type A enterotoxin in neonatal pigs. J Vet Diagn Invest,1989,1:351-353
65. Cordenonsi M, D'Atri F, Hammar E, et al. Cingulin contains globular and coiled-coil domains and interacts with ZO-1, ZO-2, ZO-3 and myosin. J Cell Biol,1999,147: 1569-1581
66. D'Andrea M R, Derian C K, Leturcq D, et al. Characterization of Protease-activated Receptor-2 Immunoreactivity in Normal Human Tissues. Journal of Histochemistry and Cytochemistry,1998,46:157-164
67. D'Andrea M R, Rogahn C J, Andrade-Gordon P. Localization of protease-activated receptors-1 and-2 in human mast cells:indications for an amplified mast cell degranulation cascade. Biotech Histochem,2000,75:85-90
68. Damiano B P, Cheung W M, Santulli R J, et al. Cardiovascular Responses Mediated by Protease-Activated Receptor-2 (PAR-2) and Thrombin Receptor (PAR-1) are Distinguished in Mice Deficient in PAR-2 or PAR-1. THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS,1999,288(2): 671-678
69. David C, Morrison, John L, et al. Endotoxins and disease mechanisms. Annual Review of Medicine,1987,38:417-432
70. Dean P, Kenny B. Intestinal barrier dysfunction by enteropathogenic Eseherichia coli is mediated by two effector molecuhs and a bacterial surface protein. Mol Microbiol, 2004,54(3):665-675
71. Derian C K, Eckardt A J, Andrade-Gordon P. Differential regulation of human keratinocyte growth and differentiation by a novel family of protease-activated receptors. Cell Growth Differ,1997,8:743-749
72. Dery O, Corvera C U, Steinhoff M, et al. Proteinase-activated receptors:novel mechanisms of signaling by serine proteases. American Journal of Physiology,1998, 274:1429-1452.
73. Ebnet K, Suzuki A, Ohno S, et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J,2001,14:3738-3748
74. Egesten A, Calafat J, Knol E F, et al. Subcellular localization of transforming growth factor-alpha in human eosinophil granulocytes. Blood,1996,87(9): 3910-3918
75. Evans D G, Evans D J, Tjoa W. Hemagglutination of human Group A erythrocytes by enterotoxigenic E. coli isolated from adults with diarrhea:correlation with colonization factor. Infect. Immun,1977,18:330-337
76. Eveline E, Schneeberger, Lynch R D. The tight junction:a multifunctional complex. Am J Physiol Cell Physiol,2004,286:C1213-C1228
77. Fasano A, Fiorentini C, Donelli G, et al. Zonula occludens toxin modulates tight junctions through p rotein kinase C-dependent actin reorganization in vitro. J Clin Invest,1995,96(6):710-720
78. Ferrell W R, Lockhart J C, Kelso E B, et al. Essential role for proteinaseactivated receptor-2 in arthritis. J Clin Invest,2003,111:35-41
79. Fiorucci S, Mencarelli A, Palazzetti B, et al. Proteinase-activated receptor 2 is an anti-inflammatory signal for colonic lamina propria lymphocytes in a mouse model of colitis. National Acad Sciences,2001,98(24):13936-13941
80. Francois Madec, Nathalie Bridoux, SteAphane Bounaix, et al. Experimental models of porcine post-weaning colibacillosis and their relationship to post-weaning diarrhoea and digestive disorders as encountered in the filed. Veterinary Microbiology,2000,72:295-310
81. Furuse M, Hirase T, Ltoh M, et al. Occludin:a novel integral membrane protein localizing at tight junctions, JCB vol,1993,123(6):1777-1788
82. Furuse M, Sasaki H, Fujimoto K, et al. A single gene product, claudin-1 or-2, reconstitutes tight junction strands and recruits occludin in fibroblasts. J Cell Biol, 1998,143:391-401
83. Gao C, Liu S, Hu H Z, et al. Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine. Gastroenterology,2002, 123:1554-1564
84. Garabal J I, Gonzalez E A, Vazquez F, et al. Serogroups of E. coli isolated from piglets in Spain. Vet. Microbiol,1996,48:113-123
85. Gerhard Rogler M D, Tilo Andus M D. Cytokines in Inflammatory Bowel Disease.world journal of surgery,1998,22:382-389
86. Giulia R, Iolanda M, Isabella V, et al. The effect of chitosan and other polycations on tight junction permeability in the human intestinal Caco22 cell line. J Nutr Biochem,2002,13(3):157-167
87. Gottardi C J, Arpin M, Fanning A S, et al. The junctionassociated protein, zonula occludens-1, localizes to the nucleus before the maturation and during the remodeling of cell-cell contacts, Proc Natl Acad Sci USA,1996,93:10779-10784
88. Green B T, Bunnett N W, Kulkarni-Narla A, et al. Intestinal type 2 proteinase-activated receptors:expression in opioid-sensitive secretomotor neural circuits that mediate epithelial ion transport. J Pharmacol Exp Ther,2000,295: 410-416
89. Gregouy M, Deitch. Role of the gut in multiple organ failure:bacterial translocation and permeability changes. World Journal of Surgery,1996,20:411-417
90. Griffin CT, Srinivasan Y, Zheng Y W, et al. A role for thrombin receptor signaling in endothelial cells during embryonic development. Science,2001,293:1666-1670
91. Haller D, Jobin C. Interaction between resident luminal bacteria and the host:can a healthy relationship turn sour? J Pediatr Gastroenterol Nutr,2004,38:123-136
92. Hampson D J. Alterations in piglet small intestinal structure at weaning. Res.Vet.Sci, 1986,40(1):32-40
93. Han X, Fink M P, Delude R L. Proinflammatory cytokines causeNO-dependent and-independent changes in exp ression and localization of tight junction p roteins in intestinal ep ithelial cells. Shock,2003,19(3):229-237
94. Harmsen M M, van Solt C B, Hoogendoorn A, et al. Escherichia coli F4 fimbriae specific llama single-domain antibody fragments effectively inhibit bacterial adhesion in vitro but poorly protect against diarrhoea. Veterinary Microbiology, 2005,111:89-98
95. He S, Aslam A, Gaca M D, et al. Inhibitors of tryptase as mast cell-stabilizing agents in the human airways:effects of tryptase and other agonists of proteinase-activated receptor 2 on histamine release. J Pharmacol Exp Ther,2004,309(1):119-126
96. Hirano K, Kanaide H. Role of Protease-activated Receptors in the Vascular System. Journal of Atheroclwrosis and Thrombosis,2003,10(4):211-225
97. Hirase T, Staddon J M, Saitou M, et al. Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci,1997,110:1603-1613
98. Hirota Y, Osuga Y, Hirata T, et al. Activation of protease-activated receptor 2 stimulates proliferation and interleukin (IL)-6 and IL-8 secretion of endometriotic stromal cells. Human Reproduction,2005,20(12):3547-3553
99. Hoevel T, Macek R, Mundigl O, et al. Expression and targeting of the tight junction protein CLDN1 in CLDN1-negative human breast tumor cells. Journal of Cellular Physiology,2002,191(1):60-68
100.Hollenberg M, Compton S J. International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors. PHARMACOLOGICAL REVIEWS,2002,54(2): 203-217
101.Hoogerwerf W A, Zou L, Shenoy M, et al. The proteinase-activated receptor2 is involved in nociception. J Neurosci,2001,21:9036-9042
102.Horiuchi T, Weller P F. Expression of vascular endothelial growth factor by human eosinophils:upregulation by granulocyte macrophage colony-stimulating factor and interleukin-5. Am J Respir cell Mol Biol,1997,17(1):70-77
103.Hou L, Kapas S, Cruchley A T, et al. Immunolocalization of proteaseactivated receptor-2 in skin:receptor activation stimulates interleukin-8 secretion by keratinocytes in vitro. Immunology,1998,94:356-362
104.Howells G L, Macey M G, Chinni C, et al. Proteinase-activated receptor-2: expression by human neutrophils. J Cell Sci,1997,110:881-887
105.Hwa J J, Ghibaudi L, Williams P, et al. Evidence for the presence of a proteinase activated receptor distinct from the thrombin receptor in vascular endothelial cells. Circ Res,1996,78:581-588
106.Imberechts H, De Greve H, Linterman P. The pathogenesis of edema disease in swine. Vet. Microbiol,1992,31:221-233
107.1osub R, Klug J, Fijak M, et al. Development of testicular inflammation in the rat involves activation of proteinase-activated receptor-2. J Pathol,2006,208:686-98
108.Jacob C, Cottrell G S, Gehringer D, et al. c-Cb1 Mediates Ubiquitination, Degradation, and Down-regulation of Human Protease-activated Receptor 2. The Journal of Biological Chemistry,2005,280:16076-16087
109.Junghyun Kim, Changsun Choi, Chanhee Chae. Prevalence of eaeA+Escherichia coli isolated from pigs with diarrhea. J Vet Diagn Invest,2001,13:355-356
110.Kahn M L, Zheng Y W, Huang W, et al. A dual thrombin receptor system for platelet activation. Narure,1998,394:690-694
111.Kanke T, Scott R, Macfarlane, et al. Proteinase-activated Receptor-2-mediated Activation of Stress-activated Protein Kinases and Inhibitory kB Kinases in NCTC 2544 Keratinocytes. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2001, 276(34):31657-31666
112.Kawabata A, Kinoshita M, Nishikawa H, et al. The protease-activated receptor-2 agonist induces gastric mucus secretion and mucosal cytoprotection. J.Clin.Invest, 2001,107(11):1443-1450
113.Kawabata A, Kuroda R, Nishida M, et al. Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland:Immunolocalization and involvement of nitric oxide in the evoked amylase secretion. Life sciences,2002,71(20):2435-2446
114.Kawabata A, Morimoto N, Nishikawa H, et al. Activation of Protease-Activated Receptor-2 (PAR-2) Triggers Mucin Secretion in the Rat Sublingual Gland. Biochemical and Biophysical Research Communications,2000,270(1): 298-302
115.Kawabata A, Saifeddine M, Al-Ani B, et al. Evaluation of proteinase-activated receptor-1 (PAR1)agonists and antagonists using a cultured cell receptor desensitization assay:activation of PAR2 by PAR1 targeted ligands. Journal of Pharmacology and Experimental Therapeutics,1999,288:358-70.
116.Kawao N, Sakaguchi Y, Tagome A, et al. Protease-activated receptor-2 (PAR-2) in the rat gastric mucosa:immunolocalization and facilitation of pepsin/pepsinogen secretion. Br J Pharmacol,2002,135(5):1292-1296
117.Kim J A, Choi S C, Yun K J, et al. Expression of protease-activated receptor 2 in ulcerative colitis. Inflammatory Bowel Diseases,2006,9(4):224-229
118.Komuro T, Miwa S, Minowa T, et al. The involvement of a novel mechanism distinct from the thrombin receptor in the vasocontraction induced by trypsin. Br J Pharmacol,1997,120:851-856
119.Kong W, McConalogue K, Khitin L M, et al. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci USA,1997, 94:8884-8889
120.Koo B H, Chung K H, Hwang K C, et al. Factor Xa induces mitogenesis of coronary artery smooth muscle cell via activation of PAR-2. FEBS Lett,2002,523:85-89
121.LanRS, Knight D A, Stewart G A, et al. Role of PGE(2) in protease-activated receptor-1,-2 and-4 mediated relaxation inthe mouse isolated trachea. Br J Pharmacol,2001,132:93-100
122.Levine M M. Escherichia Coli that cause diarrhea:enterotoxigenic,enteropa thogenic,enteroinvasive, enterohemorrhaic and enteroadherent. J.Int:Dis,1987,155: 377-389
123.Lichtenberger L M, Graziani L A, Dial E J, et al. Role of surface-active phospholipids in gastric cytoprotection. Science,1983,219(4590):1327-1329
124.Lindner J R, Kahn M L, Coughlin S R, et al. Delayed onset of inflammation in protease-activated receptor-2-deficientmice. J Immunol,2000,165:6504-6510
125.Lourbakos A, Chinni C, Thompson P, et al. Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis. FEBS Lett,1998,435:45-48
126.Lourbarkos A, Potemba J, Travis J, et al. Arginine-specific proteinase from Porphyromonas gingivalis activates proteinase-activated receptors on human oral epithelial cells and induces interlukin-6 secretion. Infect Immun,2001,69: 5121-5130.
127.Luk G D, Bayless T M, Baylin S B. Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity. J Clin Invest,1980,66(1): 66-70
128.Luk G D, Bbyleg T M, Bbylin S B. Plasma postheparin diamine oxidase sensitive p rovocative test for quantitating length of acute intestinal mucosal injury in the rat. J. clinical investigation,1983,71(5):1305-1308
129.Macfarlane S R, Seatter M J, Kanke T, et al. Proteinase-activated receptors. Pharmacol Rev,2001,53:245-282
130.Madara J L. ntestinal absorptive cell tight junctions are linked to cytoskeleton. Am J Physiol Cell Physiol,1987,253:C171-C175
131.Mahan D C, Lepine A J. Effect of pig weaning weight and associated feeding programs on subsequent performance to 105 kilograms body weight. J.Anim.Sci, 1991,69:1370-1378
132.Mainuos M R, Deitch E A, Block E F, et al. Baeterial translocation and potential role in the pathogenesis of multiple organ failure. J Intentive Care Med,1992,7: 101
133.Manela F D, Ren J, Gao J, et al. Calcitionin gene-related peptide modulates acid-regulation of somatostatatin and gastrin release from rat autrum. Gastroenterology,1995,109(3):701-706
134.Mankertz J, Tavalali S, Schmitz H, et al. Expression from the human occluding promoter is affected by tumor necrosis factor and interferon. J Cell Sci,2000,113: 2085-2090
135.Mari B, Guerin S, Far D F, et al. Thrombin and trypsin-induced Ca2+ mobilization in human T cell lines through interaction with different protease-activated receptors. FASEB J,1996,10:309-316
136.Mc Crachen B A, Spurlock M E, Roos M A, et al. Weaning anorexia may contribute to local in flammation in the piglet small intestine. Journal of Nutrition,1999,129: 613-619
137.Mclean P G, Aston D, Sarkar D, et al. Protease-activated receptor-2 activation causes EDHF-like coronary vasodilation:selective preservation in ischemia/reperfusion injury:involvement of lipoxygenase products, VR1 receptors, and C-fibers. Cirec Res,2002,90(4):465-472
138.Moffatt J D, Jeffrey K L, Cocks T M.Protease-activated receptor-2 activating peptide SLIGRL inhibits bacterial lipopolysaccharide-induced recruitment of polymorphonuclear leukocytes into the airways of mice. Am J Respir Cell Mol Biol, 2002,26:680-684
139.Miike S, Me William A S, Kita H. Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2. J Immunol,2001,167:6615-6622
140.Mirza H, Yatsula V, Bahou W F. The proteinase activated receptor-2 (PAR-2) mediates mitogenic responses in human vascular endothelial cells. J Clin Inves, 1996,97:1705-1714
141.Montalto M, Cuoco L, Ricci R, et al. Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease. Digestion, 2002,65 (4):227.
142.Morencos F C, Castano GDLH, Romas L M, et al. Small bowel bacterial overgrowth in patients with alcoholic cirrhosis. Dig Dis Sci,1996,41:552-556
143.Morrow C M K, Mruk D, Cheng C Y, et al. Claudin and occludin expression and function in the seminiferous epithelium. Phil Trans R Soc,2010,365:1679-1696
144.Mozsik G, Szolcsanyi J, Domotor A. Capsaicin research as a new tool to approach of the human gastrointestinal physiology, pathology and pharmacology. Inflammopharmacology,2008,15(6):232-245
145.Muza-Moons M M, Schneeberger E E, Hecht G A. Enteropathogenic Eschefichia coli infection leads to appearance of aberrant tight iunctions strands in the lateral membrane of intestinal eplthelial cells. Cell Microbiol,2004,6(8):783-93
146.Nagy B, Casey T A, Moon H W. henotype and genotype of E. coli isolated from pigs with ostweaning diarrhea in Hungary. J. Clin. Microbiol,1990,28: 651-653
147.Nasdala I, Wolburg-Buchholz K, Wolburg H, et al. A Transmembrane Tight Junction Protein Selectively Expressed on Endothelial Cells and Platelets. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2002,277(18):16294-16303
148.Nguyen T D, Moody M W, Steinhoff M, et al. Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2. J Clin Invest, 1999,103:261-269
149.Nishibori M, Mori S, Takahashi H K. Physiology and pathohysiology of proteinase activated receptors (PARs):PAR2 mediated proliferation of colon cancer cell. Pharmacol Sci,2005,97:25-30
150.Nishikawa H, Kawabata A, Kuroda R, et al. Characterization of protease-activated receptors in rat peritoneal mast cells. Jpn J Pharmacol,2000,82:74-77
151.Nysted S, Emilsson K, Wahlested C, et al. Molecular clonin of a potential proteinase activated receptor. Proc Natl Acad Sci USA,1994,91:9208-9212
152.Nystedt S, Ramakrishnan V, Sundelin J. The proteinaseactivated receptor 2 is induced by inflammatory mediators in human endothelial cells. Comparison with the thrombin receptor. J Biol Chem,996,271:14910-14915
153.Ohno T, Hattori Y, Komine R, et al. Roles of calcitonin gene related peptide in maintenance of gastric mucosal integrity and in enhancement of ulcer healing and angiogenesis. Gastroenterology,2008,134(1):215-225
154.Okamoto T, Nishibori M, Sawada K, et al. The effects of stimulating protease-activated receptor-1 and-2 in A172 human glioblastoma. J Neural Transm, 2001,108:125-140
155.Osek J. Prevalence of virulence factors of Escherichia coli strains isolated from diarrheic and healthy piglets after weaning. Veterinary Microbiology,1999,68: 209-217
156.Ossovskaya V S, Bunnet N W. Protease-activated receptors:contribution to physiology and disease. Physiol Rev,2004,84:579-621
157.Patel R T, Deen K I, Youngs D, et al. Interleukin 6 is a prognostic indicator of outcome in severe intra—abdominal sepsis. Br J Surg,1994,81 (9):1036-1038
158.Patel S K, Dotson J, Allen K P, et al.Identification and molecular charaterization of EatA,an autotransporter protein of enterotoxigenic Escherichia coli.Infect Imumun, 2004,72(3):1786-1794.
159.Pizzuti D, Bortolami M, Mazzon E, et al.Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten free diet. Dig Liver Dis,2004,36 (5):337
160.Ricciardolo F L, Steinhoff M, Amadesi S, et al. Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways. AmJ Respir Crit Care Med, 2000,161:1672-1680
161.Powell D W. Barrier function of ep ithelia. Am J Physiol Legacy Content,1981, 241(4):G2752288.
162.Robert H R. Inflammatory bowel disease Differential diagnosis and cancer of the small and large bowel. Digestive Diseases and Sciences,1985,30(12):1573-2568
163.Rolfe R D. The role of probiotic cultures in the control of gastrointestinal health. J Nutr,2000,130:396-402
164.Rosenfeld M G, Mermod J J, Amara S G, et al. Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing.Nature,1983, 304:129-315
165.Saifeddine M, Al-Ani B, Cheng C H, et al. Rat proteinase-activated receptor-2 (PAR-2):cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. British Journal of Pharmacology,1996,118:521-30
166.Sakakibara A, Furuse M, Saitou M, et al. Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol,1997,137:1393-1401
167.Sato K, Ninomiya H, Ohkura S, et al. Impairment of PAR-2-mediated relaxation system in colonic smooth muscle after intestinal inflammation. Br J Pharmacol, 2006,148(2):200-207
168.Schmidlin F, Amadesi S, Dabbagh K, et al. Proteaseactivated receptor 2 mediates eosinophil infiltration and hyperreactivity in allergic inflammation of the airway. J Immunol,2002,169:5315-5321
169.Schmidlin F, Amadesi S, Vidil R, et al. Expression and Function of Proteinase-activated Receptor 2 in Human Bronchial Smooth Muscle. Am. J. Respir. Crit.Care Med.,2001,164(7):1276-1281
170.Schneeberger E E, Lynch R D. The tight junction:a multifunctional complex. Am J Physiol Cell Physiol,2004,286(6):1213-1228.
171.Schultheiss M, Neumcke B, Richter H P. Endogenous trypsin receptors in Xenopus oocytes:linkage to internal calcium stores. Cell Mol Life Sci,1997,53:842-849
172.Scudamore C L, Jepson M A, Hirst B H, et al. The rat mucosal mast cell chymase, RMCP-Ⅱ, alters epithelial cell monolayer permeability in association with altered distribution of the tight junction proteins ZO-1 and occludin. Eur J Cell Biol,1998, 75(4):321
173.Sekiguchi F, Kawabata A. Protease-Activated Receptors (PARs) as Therapeutic Targets:Development of Agonists/Antagonists and Modulation of Gastrointestinal Functions. Drug Design Reviews-online,2004,1(4):287-294
174.Shifflett D E, Clayburgh D R, Koutsouris A, et al. Enteropathogenic E. coli disrupts tight junction barrier function and structure in vivo. Lab Invest,2005,85(10): 1304-1324
175.Shobha G, Narayan Raman, Simon J. Atkinson Rho GTPase signaling regulates tight junction assembly and p rotects tight junctions during ATP dep letion. Am J Physiol Cell Physiol,1999,275(3):C798-C809
176.Shpacovitch V M, Brzoska T, Bunnett N W, et al. Agonists of protease-activated receptor-2 induce cytokine release and upregulation of cell adhesion molecules in human dermal microvascular endothelial cells. J Invest Dermatol,2001,117:458-467
177.Smith R, Ransjo M, Tatarczuch L, et al. Activation of proteinase-activated receptor-2 leads to inhibition of osteoclast differentiation. J Bone Miner Res,2004,19:507-516.
178.Snoeck V, Huyghebaert N, Cox E, et al. Enteric-coated pellets of F4 fimbriae for oral vaccination of suckling piglets against enterotoxigenic Escherichia coli infections. Veterinary Immunology and Immunopathology,2003,96:219-227
179.Stanislaw J K. Gastric Cytoprotection. Scandinavian Journal of Gastroenterology, 1985,20(5):543-553
180.Steinhoff M, Buddenkotte J, Shpacovitch V, et al. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev,2005,26:1-43
181.Stenton G R, Nohara O, De'ry R E, et al. Proteinase-activated receptor (PAR)-1 and-2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 andPAR-2. J Pharmacol Exp Ther,2002,302:466-474
182.Storck J, Kusters B, Vahland M, et al. Trypsin induced von Willebrand factor release from human endothelial cells in mediated by P AR-2 activation. Thromb Res,1996, 84:463-473
183.Swisshelm K, Machl A, Planitzer S, et al. SEMP1, a senescence-associated cDNA isolated from human mammary epithelial cells, is a member of an epithelial membrane protein superfamily. Gene,1999/226(2):285-295
184.Syeda F, Grosjean J, Rebecca A, et al. Cyclooxygenase-2 Induction and Prostacyclin Release by Protease-activated Receptors in Endothelial Cells Require Cooperation between Mitogen-activated Protein Kinase and NF-KB Pathways. THE JOURNAL OF BIOLOGICAL CHEMISTRY,2006,281(17):11792-11804
185.Takagi K, Nakao M, Ogura Y, et al. Sensitive colorimetric assay of serum diamine oxidase. Clinica Chimica Acta,1994,226(1):67-75
186.Takaishi K, Sasaki T, Korani H, et al. Regulation of cell-cel adhesion by Rac and Rho small G proteins in MDCK cells. J Cell Biol,1997,139(8):1047-1059
187.Temkin V, Kantor B, Weg V, et al. Tryptase activates the mitogen-activated protein kinase/activator protein-1 pathway in human peripheral blood eosinophils, causing cytokine production and release. J Immunol,2002,169:2662-2669
188.Tina R D, Nicholas J L, Karen L H, et al. Interleukin-6 Causes Endothelial Barrier Dysfunction via the Protein Kinase C Pathway. the Annual Meeting of the Association for Academic Surgery,2001:15-17
189.Thomas A C, Cheryl J H, Robert A S, et al. Expression of Heat-Stable Enterotoxin STb by Adherent Escherichia coli Is Not Sufficient To Cause Severe Diarrhea in Neonatal Pigs. INFECTION AND IMMUNITY,1998,66(3):1270-1272
190.Tobias N M, Catherine S, Bradley M D. Zonula occludens-1 is a scaffolding protein for signalingmolecules. J Biol Chem,2002,277(28):24855-24858
191.Tobias N M, Jennifer H, Catherine S, et al. Gα12 regulates ep ithelial cell junctions through Src tyrosine kinases. Am J Physiol Cell Physiol,2003,285 (5): C1281-C1293
192.Vergnolle N, Ferazzini M, Buddenkotte J, et al. Proteinase-activated receptors:novel signals for peripheral nerves. TRENDS in Neurosciences,2003,26(9):496-500
193.Vergnolle N. Proteinase-activated receptor-2-activating peptides induce leukocyte rolling, adhesion, and extravasation in vivo. J Immunol,1999,163:5064-5069
194.Victor T, Du toit R, Van Zyl J, et al. Improved Method for the Routine Identification of Toxigenic Escherichia coli by DNA Amplification of a Conserved Region of the Heat-Labile Toxin A Subunit. JOURNAL OF CLINICAL MICROBIOLOGY,1991, 29(1):158-161
195.Vliagoftis H, Schwingshackl A, Miline C D, et al. Proteinase-activated receptor-2-mediated matrix metalloproteinase-9 release from airway epithelial cell. J Allergy Clin Immunol,2000,106(3):537-545
196.Vouret-Craviari V, Grall D, Van Obberghen-Schilling E. Modulation of rho GTPase activity in endothelial cells by selective proteinase-activated receptor (PAR) agonists. J Thromb Haemost,2003,1:1103-1111
197.VuTK, Hung D T, Wheaton V I, et al. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell,1991, 64(6):1057-1068
198.Wang Z, Wade P, Mandell K J, et al. Raf-1 represses expression of the tight junction protein occluding via activation of the zinc-finger transcription factor slug. Oncogene,2006,25(1):1-9
199.Wang Z, Wade P, Mandell K J, et al. The second loop of occludin is required for suppression of Rafl-induced tumor growth. Oncogene,2005,24(27):4412-4420
200.Wellock I J, Fortomaris P D, Houdijk J G M, et al. Effect of weaning age, protein nutrition and enterotoxigenic Escherichia coli challenge on the health of newly weaned piglets. Livestock Science,2007,108:102-105
201.Wittig W, Klie H, Gallien P, et al. Prevalence of the fimbrial antigens F18 and K88 enterotoxins and verotoxins among E. coli isolated from weaned pigs. Zbl. Bakt, 1995,283:95-104.
202.Wong V, Gumbiner B M. A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J Cell Biol,1997, 136:399-409
203.Youakim A, Ahdieh M. Interferon-gamma decreases barrier function in T84 cells by reducing ZO-1 levels and disrupting apical actin. Am J Physiol,1999,276:1279