急性肝内胆汁淤积幼鼠肠黏膜屏障损伤机制及益生菌对其干预的研究
|
摘要
第一部分
急性肝内胆汁淤积性黄疸幼鼠肠黏膜屏障损伤机制的研究
目的:为模拟人体淤胆型肝炎建立α-异硫氰酸萘酯(ANIT)诱导的急性肝内胆汁淤积性黄疸的幼鼠模型,研究急性肝内胆汁淤积性大鼠小肠粘膜屏障的变化及其机制。
方法:雄性三周龄SD大鼠ANIT50mg/kg一次性灌胃,建立急性肝内胆汁淤积动物模型,于灌胃后24、48、72小时观察各组大鼠血清总胆红素(TB)和丙氨酸转氨酶(ALT)的浓度,并采用免疫组化和Western blots免疫印迹法检测末端回肠黏膜紧密连接蛋白ZO-1(Zonula occludens-1),闭锁蛋白(Occludin),以及两种细胞因子核因子-κB (NF-κB)和肿瘤坏死因子-α(TNF-α)的分布和表达,并利用图像分析系统对Western blots图像结果进行定量分析。
结果:
1.灌服ANIT后,模型组大鼠血清ALT、TB逐渐升高,24h增加明显,48h达到高峰,72h开始下降。各时间点与对照组相比有明显差异(P<0.01)。
2. ZO-1和Occludin蛋白主要沿大鼠小肠黏膜上皮细胞膜的顶端呈线状分布,模型组大鼠24h时ZO-1和Occludin的阳性染色较对照组减少,48h减少最为明显,72h阳性染色有所恢复。Western blots结果与免疫组织化学结果相一致。各时间点与对照组相比有明显差异(P<0.01)。
3.模型组大鼠NF-κB和TNF-α蛋白表达与ZO-1和Occludin蛋白的表达呈负相关,于24h开始升高,48h达到最高点,72h开始有所下降。Western blots结果与免疫组织化学结果相一致。各时间点与对照组相比有明显差异(P<0.01)。
结论:ANIT诱导的急性肝内胆汁淤积发生时,NF-κB受刺激激活,导致炎症介质TNF-α释放增加,TNF-α可引起其他炎症介质释放增加并进一步再活化NF-κB,触发炎症介质的“瀑布样级联反应”从而导致炎症反应。由NF-κB和TNF-α介导的炎症反应引起小肠黏膜上皮紧密连接蛋白分布异常及数量改变,影响肠黏膜上皮屏障的完整性,破坏小肠黏膜屏障。
第二部分
益生菌对急性肝内胆汁淤积性黄疸幼鼠肠粘膜屏障影响
目的:研究双歧三联活菌(培菲康)对急性肝内胆汁淤积性大鼠小肠上皮细胞紧密连接蛋白ZO-1和Occludin表达的影响以及对细胞因子NF-κB和TNF-α表达的影响,从而探讨益生菌制剂对急性肝内胆汁淤积性黄疸幼鼠肠粘膜屏障的保护机制,为益生菌制剂在临床中的应用提供理论依据。
方法:雄性三周龄SD大鼠随机分为对照组、模型组和培菲康组,模型组和培菲康组均给予ANIT50mg/kg一次性灌胃,建立急性肝内胆汁淤积动物模型,培菲康组于造模前4天开始给予培菲康4.2×108个活菌数/kg/d灌胃大鼠。分别于造模后24、48、72小时三个时间点处死大鼠,取腹主动脉血检测血清TB和ALT水平,并取末端回肠黏膜组织,采用免疫组化和Western blots免疫印迹法检测紧密连接蛋白ZO-1, Occludin,以及细胞因子NF-κB和TNF-α的分布和表达,并利用图像分析系统对Western blots图像结果进行定量分析。
结果:
1.各时间点培菲康组大鼠血清ALT、TB较模型组明显降低(P<0.05)。
2.模型组大鼠24h时ZO-1和Occludin的阳性染色较对照组减少,48h减少最为明显,72h阳性染色有所恢复,而培菲康组大鼠各时间点ZO-1和Occludin的阳性染色和模型组相比均明显增多。Western blots结果与免疫组织化学结果相一致,模型组24h已经开始下降,48h达到最低,72h开始恢复,各时间点与对照组相比有明显差异(P<0.01);而培菲康组各时间点蛋白表达与模型组相应时间点数据相比有明显恢复(P<0.05)。
3.模型组大鼠NF-κB和TNF-α蛋白表达较对照组于24h开始升高,48h达到最高点,72h开始有所下降。Western blots结果与免疫组织化学结果相一致。各时间点与对照组相比有明显差异(P<0.01)。培菲康组大鼠NF-κB和TNF-α的蛋白表达与模型组大鼠在各时间点相比均明显降低(P<0.05)。
结论:双歧三联活菌能够增加急性肝内胆汁淤积性黄疸大鼠小肠黏膜上皮紧密连接蛋白ZO-1和Occludin的表达,同时能降低NF-κB和TNF-α两种细胞因子在肠道内的表达,从而降低肠道内炎症反应发生的几率,有助于恢复肠黏膜上皮屏障的完整性。
Part I
Investigation of the mechanism of the damage of intestinal mucosal barrier in rats with acute intrahepatic cholestasis
Objective: To investigate the changes of intestinal mucosal barrier in the rat models with acute intrahepatic cholestasis induced by alpha-haphtylisocyocyanate(ANIT), and explore its mechanisms.
Methods: A single dose (50 mg/kg) ofα- naphthylisothiocyanate (ANIT) was administered by gavage to each experimental rat to induce intrahepatic cholestasis. At 24h、48h and 72h after gavage, the levels of the serum total bilirubin (TB) and alanine aminotransferase(ALT) were detected and immunohistochemistry and western blot techniques were used to examine the distribution and expression of tight junction proteins—Zonula occludens-1 (ZO-1)、Occludin and two cell factors—nuclear transcription factor-kappa B (NF-κB)、tumor necrosis factor (TNF-α). And the results of Western blot were quantitative analysised by image analytical system.
Results:
1. After the administration of ANIT, the levels of serum ALT and TB in the model group increased gradually, reached the pinnache at 48h.The levels of serum ALT and TB in the model group at each time point were obviously higher than those in control group (P<0.01).
2. ZO-1 and Occludin were localized along the apical region of the lateral plasma membrane representing the region of tight junctions in surface and crypt epithelial cells. The positive stainings of ZO-1 and Occludin of model group at 24h after gavage, were decreased than those of control group, the decrease was most obviosly at 48h, and partly recovered at 72h. Western blot demonstrated consistent and significant reduction with immunohistochemistry. The protein expressions in model group were significantly lower than those in control group(P<0.01).
3. The expressions of NF-κB and TNF-αin model group were inverse correlation with the expressions of ZO-1 and Occludin. The expressions of NF-κB and TNF-αin model group were markedly higher than those in control group.
Conclusion: When Acute intrahepatic cholestasis induced by ANIT happened, NF-κB was activated and made the levels of TNF-αincreased. TNF-αcould release other mediators of inflammation and reactivated NF-κB. These could induce inflammatory reaction and the abnormal distribution of tight junction proteins and the alteration of their quantity, which affects the intestinal barrier integrity, resulting in impaired barrier function.
Part II
Effects of probiotics on the intestinal mucosal barrier in rats with experimental acute intrahepatic cholestasis
Objective: To study the effects of live combination bifidobacterium, lactobacillus and enterococcus(BIFICO) on the expressions of intestinal mucosal epithelium tight junction protein—ZO-1、Occludin and cytokine—NF-κB、TNF-αin rats with cholestasis and further discuss the protection of the probiotics to intestinal mucosal barrier, so as to provide the academic basis for its clinical uses.
Methods: Male SD rats of 3 weeks old were randomly divided into control group, model group and BIFICO group. Before making the animal model, BIFICO(4.2×108 viable bacterium counts/kg/d) were adminsterated to the rats in BIFICO group for 4 days. Model and control groups were fed by normal saline. All groups did not stop being administrated treating agent daily until executed. At the 5th day after administration, after fasting for 12h, model group and BIFICO group were intragastrically administrated ANIT(50mg/kg) for modeling. At 24h、48h and 72h after modeling, every 10 rats in each group were executed for taking abdominal aortal blood and terminal ileum tissue. The levels of serum TB and ALT were detected and immunohistochemistry and western blot techniques were used to examine the distribution and expression of tight junction proteins—ZO-1、Occludin and cell factors—NF-κB、TNF-α. And the results of Western blot were quantitative analysised by image analytical system.
Results:
1. The levels of serum ALT and TB in the BIFICO group at each time point were obviously lower than those in model group(P<0.05).
2. The positive stainings of ZO-1 and Occludin of model group at 24h after modeling, were decreased than those of control group, the decrease was most obviosly at 48h, and partly recovered at 72h. Western blot demonstrated consistent and significant reduction with immunohistochemistry. The protein expressions in BIFICO group have significant recovery compared to those in model group at each time point(P<0.05).
3. The protein expressions of NF-κB and TNF-αin BIFICO group were notably lower than those in model group at each time point(P<0.05). Conclusion: The results suggested that probiotics supplement can improve the expressions of ZO-1 and Occludin and at the same time decrease the expressions of NF-κB and TNF-αin rats with acute intrahepatic cholestasis, thereby it can cut down the probability of intestinal inflammatory reaction and conduce to improve the intestinal barrier function.
急性肝内胆汁淤积性黄疸幼鼠肠黏膜屏障损伤机制的研究
目的:为模拟人体淤胆型肝炎建立α-异硫氰酸萘酯(ANIT)诱导的急性肝内胆汁淤积性黄疸的幼鼠模型,研究急性肝内胆汁淤积性大鼠小肠粘膜屏障的变化及其机制。
方法:雄性三周龄SD大鼠ANIT50mg/kg一次性灌胃,建立急性肝内胆汁淤积动物模型,于灌胃后24、48、72小时观察各组大鼠血清总胆红素(TB)和丙氨酸转氨酶(ALT)的浓度,并采用免疫组化和Western blots免疫印迹法检测末端回肠黏膜紧密连接蛋白ZO-1(Zonula occludens-1),闭锁蛋白(Occludin),以及两种细胞因子核因子-κB (NF-κB)和肿瘤坏死因子-α(TNF-α)的分布和表达,并利用图像分析系统对Western blots图像结果进行定量分析。
结果:
1.灌服ANIT后,模型组大鼠血清ALT、TB逐渐升高,24h增加明显,48h达到高峰,72h开始下降。各时间点与对照组相比有明显差异(P<0.01)。
2. ZO-1和Occludin蛋白主要沿大鼠小肠黏膜上皮细胞膜的顶端呈线状分布,模型组大鼠24h时ZO-1和Occludin的阳性染色较对照组减少,48h减少最为明显,72h阳性染色有所恢复。Western blots结果与免疫组织化学结果相一致。各时间点与对照组相比有明显差异(P<0.01)。
3.模型组大鼠NF-κB和TNF-α蛋白表达与ZO-1和Occludin蛋白的表达呈负相关,于24h开始升高,48h达到最高点,72h开始有所下降。Western blots结果与免疫组织化学结果相一致。各时间点与对照组相比有明显差异(P<0.01)。
结论:ANIT诱导的急性肝内胆汁淤积发生时,NF-κB受刺激激活,导致炎症介质TNF-α释放增加,TNF-α可引起其他炎症介质释放增加并进一步再活化NF-κB,触发炎症介质的“瀑布样级联反应”从而导致炎症反应。由NF-κB和TNF-α介导的炎症反应引起小肠黏膜上皮紧密连接蛋白分布异常及数量改变,影响肠黏膜上皮屏障的完整性,破坏小肠黏膜屏障。
第二部分
益生菌对急性肝内胆汁淤积性黄疸幼鼠肠粘膜屏障影响
目的:研究双歧三联活菌(培菲康)对急性肝内胆汁淤积性大鼠小肠上皮细胞紧密连接蛋白ZO-1和Occludin表达的影响以及对细胞因子NF-κB和TNF-α表达的影响,从而探讨益生菌制剂对急性肝内胆汁淤积性黄疸幼鼠肠粘膜屏障的保护机制,为益生菌制剂在临床中的应用提供理论依据。
方法:雄性三周龄SD大鼠随机分为对照组、模型组和培菲康组,模型组和培菲康组均给予ANIT50mg/kg一次性灌胃,建立急性肝内胆汁淤积动物模型,培菲康组于造模前4天开始给予培菲康4.2×108个活菌数/kg/d灌胃大鼠。分别于造模后24、48、72小时三个时间点处死大鼠,取腹主动脉血检测血清TB和ALT水平,并取末端回肠黏膜组织,采用免疫组化和Western blots免疫印迹法检测紧密连接蛋白ZO-1, Occludin,以及细胞因子NF-κB和TNF-α的分布和表达,并利用图像分析系统对Western blots图像结果进行定量分析。
结果:
1.各时间点培菲康组大鼠血清ALT、TB较模型组明显降低(P<0.05)。
2.模型组大鼠24h时ZO-1和Occludin的阳性染色较对照组减少,48h减少最为明显,72h阳性染色有所恢复,而培菲康组大鼠各时间点ZO-1和Occludin的阳性染色和模型组相比均明显增多。Western blots结果与免疫组织化学结果相一致,模型组24h已经开始下降,48h达到最低,72h开始恢复,各时间点与对照组相比有明显差异(P<0.01);而培菲康组各时间点蛋白表达与模型组相应时间点数据相比有明显恢复(P<0.05)。
3.模型组大鼠NF-κB和TNF-α蛋白表达较对照组于24h开始升高,48h达到最高点,72h开始有所下降。Western blots结果与免疫组织化学结果相一致。各时间点与对照组相比有明显差异(P<0.01)。培菲康组大鼠NF-κB和TNF-α的蛋白表达与模型组大鼠在各时间点相比均明显降低(P<0.05)。
结论:双歧三联活菌能够增加急性肝内胆汁淤积性黄疸大鼠小肠黏膜上皮紧密连接蛋白ZO-1和Occludin的表达,同时能降低NF-κB和TNF-α两种细胞因子在肠道内的表达,从而降低肠道内炎症反应发生的几率,有助于恢复肠黏膜上皮屏障的完整性。
Part I
Investigation of the mechanism of the damage of intestinal mucosal barrier in rats with acute intrahepatic cholestasis
Objective: To investigate the changes of intestinal mucosal barrier in the rat models with acute intrahepatic cholestasis induced by alpha-haphtylisocyocyanate(ANIT), and explore its mechanisms.
Methods: A single dose (50 mg/kg) ofα- naphthylisothiocyanate (ANIT) was administered by gavage to each experimental rat to induce intrahepatic cholestasis. At 24h、48h and 72h after gavage, the levels of the serum total bilirubin (TB) and alanine aminotransferase(ALT) were detected and immunohistochemistry and western blot techniques were used to examine the distribution and expression of tight junction proteins—Zonula occludens-1 (ZO-1)、Occludin and two cell factors—nuclear transcription factor-kappa B (NF-κB)、tumor necrosis factor (TNF-α). And the results of Western blot were quantitative analysised by image analytical system.
Results:
1. After the administration of ANIT, the levels of serum ALT and TB in the model group increased gradually, reached the pinnache at 48h.The levels of serum ALT and TB in the model group at each time point were obviously higher than those in control group (P<0.01).
2. ZO-1 and Occludin were localized along the apical region of the lateral plasma membrane representing the region of tight junctions in surface and crypt epithelial cells. The positive stainings of ZO-1 and Occludin of model group at 24h after gavage, were decreased than those of control group, the decrease was most obviosly at 48h, and partly recovered at 72h. Western blot demonstrated consistent and significant reduction with immunohistochemistry. The protein expressions in model group were significantly lower than those in control group(P<0.01).
3. The expressions of NF-κB and TNF-αin model group were inverse correlation with the expressions of ZO-1 and Occludin. The expressions of NF-κB and TNF-αin model group were markedly higher than those in control group.
Conclusion: When Acute intrahepatic cholestasis induced by ANIT happened, NF-κB was activated and made the levels of TNF-αincreased. TNF-αcould release other mediators of inflammation and reactivated NF-κB. These could induce inflammatory reaction and the abnormal distribution of tight junction proteins and the alteration of their quantity, which affects the intestinal barrier integrity, resulting in impaired barrier function.
Part II
Effects of probiotics on the intestinal mucosal barrier in rats with experimental acute intrahepatic cholestasis
Objective: To study the effects of live combination bifidobacterium, lactobacillus and enterococcus(BIFICO) on the expressions of intestinal mucosal epithelium tight junction protein—ZO-1、Occludin and cytokine—NF-κB、TNF-αin rats with cholestasis and further discuss the protection of the probiotics to intestinal mucosal barrier, so as to provide the academic basis for its clinical uses.
Methods: Male SD rats of 3 weeks old were randomly divided into control group, model group and BIFICO group. Before making the animal model, BIFICO(4.2×108 viable bacterium counts/kg/d) were adminsterated to the rats in BIFICO group for 4 days. Model and control groups were fed by normal saline. All groups did not stop being administrated treating agent daily until executed. At the 5th day after administration, after fasting for 12h, model group and BIFICO group were intragastrically administrated ANIT(50mg/kg) for modeling. At 24h、48h and 72h after modeling, every 10 rats in each group were executed for taking abdominal aortal blood and terminal ileum tissue. The levels of serum TB and ALT were detected and immunohistochemistry and western blot techniques were used to examine the distribution and expression of tight junction proteins—ZO-1、Occludin and cell factors—NF-κB、TNF-α. And the results of Western blot were quantitative analysised by image analytical system.
Results:
1. The levels of serum ALT and TB in the BIFICO group at each time point were obviously lower than those in model group(P<0.05).
2. The positive stainings of ZO-1 and Occludin of model group at 24h after modeling, were decreased than those of control group, the decrease was most obviosly at 48h, and partly recovered at 72h. Western blot demonstrated consistent and significant reduction with immunohistochemistry. The protein expressions in BIFICO group have significant recovery compared to those in model group at each time point(P<0.05).
3. The protein expressions of NF-κB and TNF-αin BIFICO group were notably lower than those in model group at each time point(P<0.05). Conclusion: The results suggested that probiotics supplement can improve the expressions of ZO-1 and Occludin and at the same time decrease the expressions of NF-κB and TNF-αin rats with acute intrahepatic cholestasis, thereby it can cut down the probability of intestinal inflammatory reaction and conduce to improve the intestinal barrier function.
引文
[1] Garcia-Tsao G. Bacterial translocation: cause or consequence of decompensation in cirrhosis? J Hepatol 2001; 34: 150-155.
[2] Olah A, Belagyi T, Issekutz A, et al. Randomized clinical trial of special lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis [ J ]. Br J Surg, 2002, 89 ( 9) : 1103-1107.
[3] Rayes N, Seehofer D, Muller AR. Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery results of aprospective trial [ J ].Z Gastroenterol, 2002, 40 (10) : 869-876.
[4] Hillstrom J, Duane WC, Eckfeldt JH, et al. Lack of benefit of ursodeoxycholic acid in drug-induced cholestasis in the rat. Proc Soc Exp Biol Med, 1992; 200(1):122-126.
[5] Goldfarb S, Singer EJ, Popper H. Experimental cholangitis due to alpha- naphthylisothiocya-nate(ANIT). Am J Pahtol, 1962;40:685-698.
[6] Rolo AP, Oliweira PJ, Seica R, et al. Disruption of mitochondrial calcium homeostasis after chronic alpha-naphthylisothiocyanate administration: relevance for cholestasis. J Investing Med, 2002;50(3):193-200.
[7] Schaffner F, Scharnbeck HH, Hutterer F, et al. Mechanism of cholestasis. VII.a-Naphthylisothiocyanate-induced jaundice. Lab Invest. 1973;82:321-331.
[8] Krell H, Hoke H, Pfaff E. Development of intrahepatic cholestasis by a-Naphthylisothiocynate in rates. Gatroenterology. 1982;82:507-514.
[9] Connolly AK, Price SC, Connelly JC, et al. Early changes in bile duct lining cells and hepatocytes in rats treated with alpha-Naphthylisothioyanate. Toxicol Appl Pharmacol. 1988;93(2):208-219.
[10] Roth RA, Dahm LJ. Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate. Drug Metab Rev. 1997;29:153-165.
[11] Dietrich CG, Ottenhoff R, de Waart DR, et al. Role of MRP2 and GSH intrahepatic cycling of toxins. Toxicology. 2001;167:73-81.
[12] Jean PA, Bailie MB, Roth RA. 1-naphthylisothiocyanate-induced elevation of biliary glutathione. Biochem Pharmacol. 1995;49(2):197-202.
[13] Li MK, Crawford JM. The pathology of cholestasis. Semin Liver Dis. 2004;24(1):21-42.
[14] Santa Cruz V, Dugas TR, Kanz MF. Mitochondrial dysfunction occurs before transport or tight junction deficits in biliary epithelial cells exposed to bile from methylenedianiline-treated rats.Toxicol Sci. 2005;84(1):129-138.
[15] Roth RA, Dahm LJ. Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate. Drug Metab Rev. 1997;29:153-165.
[16] Dahm LJ, Schultze AE, Roth RA. An antibody to neutrophils attenuates alpha-naphthylisothiocyanate-induced liver injury. J Pharmacol Exp Ther. 1991;256(1):412-420.
[17] Hill DA, Roth RA. Alpha-naphthylisothiocyanate causes neutrophils release factors that are cytotoxic to hepatocytes. Toxicol Appl Pharmacol. 1998;148(1):169-175.
[18] Hill DA, Jean PA, Roth RA. Bile duct epithelial cells exposed to alpha- naphthylisothiocyanate produce a factor that causes neutron-phil-dependent hepatocellular injury in vitro. Toxicol Sci. 1999;47:18-25.
[19] Kongo M, Ohta Y, Nishida K, et al. An association between lipid peroxidation and ANIT induced hepaticellar injury in vitro. Toxicol Lett. 1999;105:103-110.
[20] Ohta Y, Kongo M, Sasaki E, et al. Change in hepatic antioxidant defense system with liver injury development in rats with a single a-naphthy-lisothiocyanate intoxication. Toxiology. 1999;139:265-275.
[21] Ohta Y, Kongo M, Kishikawa T, et al. Preventive effect of melatonin on the progression of A-naphthylisothiocyanate-induced acute liver injury in rats. J Pineal Res. 2003;34:185-193.
[22]黄欣,黄志华.微生态制剂对肝内胆汁淤积性肝损伤兔模型胆汁和血清TNF-α和IL-6的影响.中国微生态学杂志,2003,15(3):137-140.
[23]刘凡,王晓东,黄志华.可溶性细胞间黏附分子在急性肝内胆汁淤积模型中的表达.实用儿科临床杂志,2006;21(19)1303-1304.
[24] Xu J, Lee G, Wang H, et al. Limited role for CXC chemokines in the pathogenesis of alpha--naphthylisothiocyanate-induced liver injury. Am. J. Physiol. Gastrointest. Liver Physiol. 2004;287:734-741.
[25] Kim ND, Moon JO, Slitt AL, et al. Early growth response factor-1 is critical for cholestatic liver injury. Toxicol Sci. 2006;90(2):586-595.
[26] Wong V. Phosphorylation of occludin correlates with occludin localization and function at the tight junction. Am J Physiol, 1997, 273(6 Pt 1): C1859-C1867.
[27] Harari Y, Weisbrodt NW, Moody FG. Ileal mucosal response to bacterial toxin challenge. J Trauma 2000;49: 306-313.
[28] Kiyono H, Kweon MN, Hiroi T, Takahashi I. The mucosal immune system: from specialized immune defense to infl ammation and allergy. Acta Odontol Scand 2001; 59: 145-153.
[29] Assimakopoulos SF , Vagianos CE , Pat soukis N , et al . Evidence for intestinal oxidative st ress in obst ructive jaundice2induced gut barrier dysfunction in rat s. Acta Physiol Scand , 2004 , 180 : 177-185.
[30]朱维铭,李宁.肠内营养[J].中国实用外科杂志,2001,21 (8):506-510.
[31]于晓明,金宏,糜漫天.肠屏障功能的损伤与营养素防护[J].解放军预防医学杂志,2006,24(1):74-76.
[32] Reynolds JV, Murchan P, Leonard N, et al. Gut barrier failure in experimental obstructive jaundice. J Surg Res,1996, 62:11-16.
[33] Sileri P, Morini S, Sica GS, et al. Bacterial translocation and intestinal morphological findings in jaundiced rats. Dig Dis Sci, 2002, 47: 929-934.
[34] Gencay C, Kilicoglu SS, Kismet K, et al. Effect of honey on bacterial translocation and intestinal morphology in obstructive jaundice. World J Gastroenterol, 2008, 14(21):3410-3415.
[35] Parks RW, Stuart Cameron CH, Gannon CD, et al. Changes in gastrointestinal morphology associated with obstructive jaundice. J Pathol, 2000, 192(6): 526-532.
[36]岳茂兴.胃肠道功能障碍及衰竭的诊断和治疗.世界华人消化杂志2002; 10: 3-6.
[37] Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001;2: 285-293.
[38] Nusrat A, Parkos CA, Liang TW, Carnes DK, Madara JL. Neutrophil migration across model intestinal epithelia: monolayer disruption and subsequent events in epithelial repair. Gastroenterology 1997; 113: 1489-1500.
[39] Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 2000; 279: G851-857.
[40]宋红丽,吕飒,马力,李颖,刘沛. TNF-alpha影响肠黏膜上皮细胞间紧密连接蛋白的表达.世界华人消化杂志2004; 12: 1303-1306.
[41] Junichi L, Kazuaki U, Sachiko T, et al. Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization[J]. J Cell Biology, 2007,176(6): 779-786.
[42] Matter Ka, Balda MS. Signaling to and from tight junctions[J]. Nat Rev Mol Cell Biol, 2003, 4(3): 225-236.
[43] Michael B, Fallon AR, Balda MS, et al. Altered hepatic localization and expression of occluding after common bile duct ligation. Am J Physiol, 1995, 269(38): 1057-1062.
[44] Assimakopoulos SF, Scopa CD, Charonis A, et al. Experimental obstructive jaundice disrupts intestinal mucosal barrier by altering occludin expression: beneficial effect of bombesin and neurotensin. J Am Coll Surg, 2004,198(5): 748-757.
[45]陈振勇,冯贤松,周有生.梗阻性黄疸大鼠肠黏膜上皮紧密连接蛋白和MLCK的研究.中国普通外科杂志, 2008,17(2): 140-144.
[46] Yang R, Harad T, Li J, et al . Bile modulates intestinal epithelial barrier function via an ext racellular signal related kinase 1/2 dependent mechanism. Intensive Care Med, 2005, 31(5):709-717.
[47] Portincasa P, Grattagliano I, Testini M, et al. Parallel intestinal and liver injury during early cholestasis in the rat: modulation by bile salts and antioxidants. Free Radic Biol Med, 2007, 42: 1381-1391.
[48] Bemelmans MH, Gouma DJ, Greve JW, et al. Cytokines tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice. Hepatology, 1992, 15:1132-1136.
[49] Schmitz H, Fromm M, Bentzel CJ, et al. Tumor necrosis factor-alpha(TNFalpha) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. J Cell Sci, 1999, 112:137-146.
[50] Blikslager AT, Roberts MC. Nitric oxide and the intestinal epithelial barrier: does it protect or damage the gut? J Pediar Gastroenterol Nutr, 1997, 25: 439-440.
[51] Hiscott J, Kwon H, Genin P. Hostile takeovers: viral appropriation of the NF-kapppaB pathway. J Clin Invest,2001;107(2):143-151.
[52] DETHASE M, LIX, KARIN M. Kinase regulation in inflammatory response[J].Nature, 2000, 406 (27) : 267-268.
[53] NEISH A S, GEWIRTZA T, ZENG Hui, et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-aubiquitination[J]. Science,2000, 289: 1560-1563.
[54] Mankertz J, Tavalali S, Schmitz H, et al. Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci, 2000, 113:2085-2090.
[55] McCarthy KM, Skare IB, Stankewich MC,et al. Occludin is a functional component of the tight junction. J Cell Sci. 1996,109:2287-2298.
[56] Han X, Fink MP, Delude RL. Proinflammatory cytokines cause NO-dependent and–independent changes in expression and lacalization of tight junction proteins in intestinal epithelial cells. Shock. 2003,19(3):229-237.
[57] Sappington PL, Han X, Yang R, et al. Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated caco-2 enterocytic monolayers. J Pharmacol Exp Ther. 2003,304(1):464-476.
[58] Fasano A, Fiorentini C, Donelli G, et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization in vitro. J Clin Invest,1995, 96(6):710-720.
[59] Nakajima Y, Baudry N, Duranteau J, et al. Microcirculation in intestinal villi: a comparison between hemorrhagic and endotoxin shock. Am J Respir Crit Care Med, 2001, 164:1526-1530.
[60] Tsukamoto T, Nigam SK. Role of tyrosine phosphorylation in the reassembly of occludin and other tight junction proteins. Am J Physiol, 1999, 276: F737-F750.
[61] Wells CL, Jechorek RP, Erlandsen SL. Inhibitory effect of bile on bacterial invasion of enterocytes: possible mechanism for increased translocation associated with obstructive jaundice. Crit Care Med, 1995, 23: 301-307.
[62] Simonovic I, Rosenberg J, Koutsouris A, et al. Enteropathogenic Escherichia coil dephosphorylates and dissociates occludin from intestinal epithelial tight junctions.Cell Microbiol, 2000, 2: 305-315
[63] Assimakopoulos SF, Thomopoulos KC, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest, 2006,36: 181-187.
[64] Sakaguchi S, Furusawa S, Yokota K, et al. The enhancing effect of tumour necrosis factor alpha on oxidative stress in endotoxemia. Pharmacol Toxicol, 1996, 79: 259-265.
[65] Pata C, Caglikulekci M, Cinel L, et al. The effects of antithrombin-III on inducible nitric oxide synthesis in experimental obstructive jaundice. Pharmacol Res, 2002, 46:325-331.
[66] Tsuji K, Kubota Y, Yamamoto S, et al. Increased neutrophil chemotaxis in obstructive jaundice: an in vitro experiment in rats. J Gastroenterol Hepatol, 1999, 14: 457-463.
[67] Tsai LY, Lee KT, Lu FJ. Biochemical events associated with ligation of the common bile duct in Wistar rats. J Formos Med Assoc, 1997, 96: 17-22.
[68] Rao RK, Basuroy S, Rao VU, et al.Tyrosine phosphorylation and dissociation of occludin, ZO-1 and E-cadherin-beta-catenin complexes form the cytoskeleton by oxidative stress. Biochem J, 2002, 368: 471-481.
[69] Assimakopoulos SF, Scopa CD, Zervoudakis G, et al. Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice. Ann Surg, 2005, 241: 159-167.
[70] Rinne M, Kallimaki M,Arvilommi H,et al.Effect of probiotics and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral immune responses[J].J Pediatr,2005,147(2):186-191.
[71] Gill H S,Rutherfurd K J,Cross M L.Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes[J].J Clin Immunol,2001,21(4):264-271.
[72] Fujihashi K, Dohi T, Rennert PD et al. Peyer,s patches are required for oral toleranceto proteins[J]. Pnas, 2001, 98(6):3310-3315.
[73] Baia P, Ouyang Q, Xiao X R, et al. Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis [J].J Appl Microbiol, 2004,97(1):29-37.
[74] Andrew S. Neish, Andrew T. Gewirtz, Hui Zeng, et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-a ubiquitination. Science. 2000, 289:1560- 1563.
[75]周长玉,王江滨.益生菌治疗炎症性肠病的研究进展[J].国外医学消化系疾病分册,2004,24(3):172-174.
[76] Ewaschuk J B, Backer J L, Churchill T A, et al. Surface expression of Toll-like receptor 9 is up regulated on intestinal epithelial cells in response to pathogenic bacterial DNA[J].Infect Immun,2007,75(5):2572-2579.
[77] Resta-lenert S,Barrett K E.Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli(EIEC)[J]. Gut,2003,52(7): 988-997.
[78] Korzenik J R,Podolsky D K.Evolving knowledge and therapy of inflammatory bowel disease[J].Nat Rev Drug Discov,2006,5(3):197-209.
[79] Van Gossum A,Dewit O,Louis E,et al.Multicenter randomized controlled clinical trial of probiotics (Lactobacillus johnsonii,LA1) on early endoscop ic recurrence of Crohn′s disease after ileo-caecal resection[J].Inflamm Bowel Dis,2007,13(2):135- 142.
[80] Ko J S, Yang H R, Chang J Y, et al. Lactobacillus plantarum inhibits ep- ithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-alpha[ J ]. World J Gastroenterol, 2007, 13 (13) :1962-1975.
[81] Zyrek AA, Cichon C, Helms S, et al. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol.2007,9(3):804-816.
[82] Madsen K, Cornish A, Soper P, et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function[J]. Gastroenterology,2001,121:(3) 580-591.
[83] Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli(EIEC)[J].Gut, 2003,52 (7):988-997.
[84]王斌,但国蓉,等.乳杆菌黏附抑制致病性大肠杆菌对肠上皮样细胞侵袭的初步研究[ J ].解放军医学杂志, 2006, 31 (6):550-552.
[85]胡玉莲,黄志华,王晓东.双歧三联活菌片对淤胆幼鼠移行性肌电复合波影响及其干预胆汁淤积机制探讨[J].实用儿科临床杂志,2007,22(19):1487-1489.
[86] Neish A S, GewirtzAT, Zeng H, et al. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination[J].Science,2000,289 (5484):1560-1563.
[87] Bai A P, Ouyang Q, Xiao X R, et al. Probioticsmodulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis[J]. International Journal of Clinical Practice, 2006, 60(3):284-288.
[88] Kim Y G, Ohta T, Takahashi T, et al. Probiotic Lactobacillus casei activates innate immunity via NF-kappaB and p38 MAP kinase signaling pathways[J].Microbes & Infection, 2006, 8 (4):994-1005.
[89] Madsen K L, Doyle J S, Jewell L D, et al. Lactobacillus species prevents colitis in interleukin 10 gene2deficient mice [J]. Gastroenterology, 1999,116(5):1107-1114.
[90] Ko J S, Yang H R, Chang J Y, et al. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-alpha[ J ]. World J Gastroenterol, 2007,13(13):1962-1975.
[91] Bruewer M, Luegering A, Kucharzik T, et al. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms[J]. J Immunol, 2003, 171 (11):6164-6172.
[92] Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinalepithelial cells[J]. J Biol Chem, 2002, 277(52):50959-50965.
[93] Borruel N, CarolM, Casellas F, et al. Increased mucosal tumour necrosis factor alpha production in Crohn’s disease can be down-regulated ex vivo by probiotic bacteria [ J ]. Gut, 2002, 51(5):659-664.
[94] Carol M, Borruel N, Antolin M, et al. Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn’s disease[J]. Journal of Leukocyte Biology, 2006,79(5):917-922.
[95] Dubuquoy L, Jansson EA, Deeb S, et al. Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis[ J ]. Gastroenterology, 2003, 124(5):1265-1276.
[96] Kelly D, Campbell J I, King TP, et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytop lasmic shuttling of PPAR-gamma and RelA [ J ]. Nature Immunology, 2004, 5(1):104-112.
[97] Carmen Collado M, Jussi M, Seppo S. In vitro analysis of probiotic strain combinations to inhibit pathogen adhesion to human intestinalmucus[J].Food Res Intern,2007,40(5):629-636.
[98] Park J H, Umj I, Lee B J, et al. Encapsulated bifidobcterium bifidum potentiates intestinal IgA production[J].Cell Immunol,2002,219(1):22-27.
[99] Gionchetti P,Rizzello F,Helwigu,et al.Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial[J].Gastroenterology, 2003,124(5): 1202-1209.
[1] Liboni KC, Li N, Scumpia PO, Neu J. Glutamine modulates LPS-induced IL-8 production through IkappaB/NF-kappaB in human fetal and adult intestinal epithelium. J Nutr 2005; 135: 245-251.
[2]马涛,尤胜义.淋巴细胞凋亡,免疫抑制和脓毒症.国外医学?外科学分册2005; 32: 35-38.
[3]杨书良,李兰梅,陈育民.肠黏膜屏障的构成与功能研究进展.临床荟萃2008; 23: 1809-1811.
[4] Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut 2006; 55: 1512-1520.
[5] Barrett KE. New ways of thinking about (and teaching about) intestinal epithelial function. Adv Physiol Educ 2008; 32: 25-34.
[6] Deitch EA. Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings? Surgery 2002; 131:241-244.
[7]黎介寿.肠衰竭-概念:营养支持与肠黏膜屏障维护.肠外与肠内营养2004;11: 65-67.
[8] Walser EM, Nealon WH, Marroquin S, Raza S, Hernandez JA, Vasek J. Sterile fluid collections in acute pancreatitis: catheter drainage versus simple aspiration. Cardiovasc Intervent Radiol 2006; 29:102-107.
[9]刘春峰,袁壮.内脏缺血缺氧代谢障碍在SIRS和MODS中的作用[J ] .小儿急救医学,2000 ,7 (4) :180-182.
[10] Secchi A ,Ortanderl JM ,Schmidt W, et al . Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats [J] . J Surg Res ,2000 ,89 (1):26-30.
[11] Boros M , Takaichi S , Hatanaka K. Ischemic time-dependent microvascular changes and reperfusion injury in the rat small intestine[J].J Surg Res,1995,59 (2):311-320.
[12] Mitsuoka H ,Schmid2Schonbein GW. Mechanisms for blockade of in vivo activator production in the ischemic intestine and multiorgan failure[J].S hock ,2000 ,14 (5):522-527.
[13]张嘉,刘瑞林,刘牧林.肠道屏障功能损伤机制的研究进展.蚌埠医学院学报2005; 30: 277-279.
[14]刘晓臣,彭燕.肠屏障功能障碍与重症急性胰腺炎.世界华人消化杂志2006; 14: 3131-3135.
[15] Vallance BA, Dijkstra G, Qiu B, van der Waaij LA, van Goor H, Jansen PL, Mashimo H, Collins SM. Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity. Am J Physiol Gastrointest Liver Physiol 2004; 287: G865-G74.
[16]王嘉川.内毒素血症在重症肝炎发病中的作用.寄生虫与感染性疾病2006; 4: 40-41.
[17]高金生,时志民,韩转叶,李校天,杨书良.肝硬化肠黏膜屏障损伤患者血浆D-乳酸、二胺氧化酶及内毒素的变化.临床荟萃2009; 24: 219-221.
[18]蒋朱明,于康.肠黏膜屏障损害与肠外和肠内营养[J].外科理论与实践,2000,5 (1) ;54-56.
[19] De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients:effect of glutamine. Crit Care Med 2005; 33:1125-1135.
[20] Singleton KD, Wischmeyer PE. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia. Shock 2006; 25: 295-299.
[21] Ikeda H, Suzuki Y, Suzuki M , et al . Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/ reperfusion injury to the rat intestinal epithelium[J ] . Gut ,1998 ,42 (4) :530-537.
[22]王兴鹏,王冰娴,吴恺,等.细胞凋亡在急性坏死型胰腺炎早期肠黏膜上皮细胞死亡中的作用[J ] .中华消化杂志,2001 ,21(5):267-270.
[23]周德俊,王鹏志,朱理玮,等. Bcl22基因在供体小肠缺血再灌注损伤中作用的实验研究[J ] .中华普通外科杂志,1999 ,14(1):76-77.
[24] Hawrelak JA, Myers SP. The causes of intestinal dysbiosis: a review. Altern Med Rev 2004; 9: 180-197.
[25] Kanauchi O, Mitsuyama K, Araki Y, Andoh A.Modification of intestinal flora in the treatment of inflammatory bowel disease. Curr Pharm Des 2003; 9:333-346.
[26] Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics.Gastroenterology 2004; 126: 1620-1633.
[27] Dotan I, Rachmilewitz D. Probiotics in inflammatory bowel disease: possible mechanisms of action. Curr Opin Gastroenterol 2005; 21: 426-430.
[28]李兰娟.感染与微生态学.第1版.北京:人民卫生出版社, 2002: 295-300.
[29] Lewis K, Caldwell J, Phan V, et al. Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-alpha.Am J Physiol Gastrointest Liver Physiol 2008; 294:G669-G678.
[30]白爱平.炎症性肠病肠黏膜屏障损伤机制.世界华人消化杂志2008; 16: 3187- 3191.
[31]何新颖,唐志鹏,张亚丽.肠上皮屏障与炎症性肠病研究进展.世界华人消化杂志2008; 16: 3316-3320.
[32] [32] Hoyt DB ,J unger WG,Loomis WH , et al . Effects of trauma on immune cell function : Impairment of intracellular calcium signaling[J ].S hock ,1994,2 (1):23-28.
[33]于勇,盛志勇,田惠民,等.大鼠烫伤后肠道免疫屏障损伤的实验研究[J ] .中华整形烧伤外科杂志,1996 ,12 (2) :86-89.
[34] Chen LW,Hsu CM ,Huang J K, et al . Effects of bombesin on gut mucosal immunity in rats after thermal injury[J ]. J Formos Med Assoc,2000 ,99 (6):491-498.
[35] Wang X , Andersson R. Soltesz V , et al . Gut origin sepsis, Macrophage function ,and oxygen extraction associated with acute pancreatitis in the rat [J ].World J Surg, 1996, 20 (3):299-308.
[36]陈意生,史景泉.多器官功能障碍综合征的病理基础[J].创伤外科杂志,2001,3 (1):72-74.
[37]陈德昌.多器官功能障碍综合征[A].见:吴阶平,裘法祖主编.黄家驷外科学[M].第6版.北京:人民卫生出版社,2000 :400-429.
[1] Vining DJ,Gelfand DW,Bechtold RE,et al.Technical feasibility of colon imaging with helical CT and virtual reality.AJR,1994,162:104-118.
[2]李子平,许达生,孟悛非,等.CT仿真内窥镜成像技术临床应用的初步探讨.中华放射学杂志,1998,32:104-107.
[3]张镭,瞿晓力,李杰,等.CT仿真结肠内窥镜的临床应用研究.中华放射学杂志,1999,33:171-174.
[4] Sudha Anupindi,James Perumpillichira,Esther J,et al. Low-dose CT colonography in children:initial experience,technical feasibility,and utility.Pediatr Radiol, 2005, 35:518-524.
[5] Capu?ay CM, Carrascosa PM, Bou-Khair A,Low radiation dose multislice CT colonography in children: Experience after 100 studies. Eur J Radiol.2005 56(3): 398-402.
[6] Hara AK,Johnson CD,MacCarty RL,et al. Incidental extracolonic findings at CT colonography. Radiology,2000,215(2):353-357.
[7] Hara AK,Johnson CD,MacCarty RL,et al. CT colonography: single- versus multi-detector row imaging. Radiology,2001,219(2):461-465.
[8] Fenlon HM,Nunes DP,Schroy PC 3rd,et al. A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med,1999,341(20): 1496-1503.
[9] Fletcher JG,Johnson CD,Welch TJ,et al. Optimization of CT colonography technique: prospective trial in 180 patients. Radiology,2000,216(3):704-711.
[10] Yee J,Akerbar GA,Hung RK,et al.Characteristics of CT colonography for the detection of colorectal neoplasia in 300 patients.Radiology,2001,219:685.
[11] Laghi A,Iannaccone R,Carbone I, et al.Multislice spiral CT colonography for the detection of colorectal polyps and neoplasms.Radiology,2001,221:307.
[12] Fenlon HM, McAneny DB,Nunes DP,et al. Occlusive colon carcinoma: virtual colonoscopy in the preoperative evaluation of the proximal colon. Radiology,1999,210(2):423-428.
[13] Royster AP,Fenlon HM,Clarke PD,et al. CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation.AJR Am J Roentqenol,1997,169(5):1237-1242.
[14]余深平,李子平,许达生,等.大肠充气螺旋CT扫描图像后处理功能的临床应用[J].中华放射学杂志,2000,34(5):295-299.
[15]张晓鹏,徐刚,徐舟,等.胃肠道螺旋CT三维成像方法及临床应用评价[J] .中华放射学杂志,2000,34(5):308-312.
[16] Carrascosa P, Capunay C, Bou-Khair A,et al.Virtual colonoscopy:is it a useful method in pediatrics? First experience (abstr).Eur Radiol,2001 (Supplement 1):322.
[17]翟晓力,张镭,翟仁友,等. CT结肠造影技术的临床初步应用—并与双对比钡灌肠对照[J].中华放射学杂志,2000,34(5):300-303.
[18] Chung DJ,Huh KC,Choi WJ,et al.CT colonography using 16-MDCT in the evaluation of colorectal cancer.Am J Roentgenol,2005,184(1):98-103.
[19] Dachman AH, Zalis ME. Quality and consistency in CT colonography and research reporting.Radiology 2004,230:319-323.
[20] Cotton PB, Durkalski VL, Pineau BC, et al. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA 2004,291(14):1713-1719.
[21] Luo MY, Shan H, Yao LQ, et al. Postprocessing techniques of CT colonography in detection of colorectal carcinoma. World J Gastroenterol 2004,10(11):1574-1577.
[22] Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003,349:2191- 2200.
[23] Carrascosa P, Capunay C, Castiglioni R, et al. Virtual colonoscopy. Experience in 500 patients. Acta Gastroenterol Latinoam 2003,33(3):145-149.
[24]许达生,余深平.进一步提高结肠CT仿真内窥镜的诊断水平[J ].中华放射学杂志,2000,34(5):293-294.
[2] Olah A, Belagyi T, Issekutz A, et al. Randomized clinical trial of special lactobacillus and fibre supplement to early enteral nutrition in patients with acute pancreatitis [ J ]. Br J Surg, 2002, 89 ( 9) : 1103-1107.
[3] Rayes N, Seehofer D, Muller AR. Influence of probiotics and fibre on the incidence of bacterial infections following major abdominal surgery results of aprospective trial [ J ].Z Gastroenterol, 2002, 40 (10) : 869-876.
[4] Hillstrom J, Duane WC, Eckfeldt JH, et al. Lack of benefit of ursodeoxycholic acid in drug-induced cholestasis in the rat. Proc Soc Exp Biol Med, 1992; 200(1):122-126.
[5] Goldfarb S, Singer EJ, Popper H. Experimental cholangitis due to alpha- naphthylisothiocya-nate(ANIT). Am J Pahtol, 1962;40:685-698.
[6] Rolo AP, Oliweira PJ, Seica R, et al. Disruption of mitochondrial calcium homeostasis after chronic alpha-naphthylisothiocyanate administration: relevance for cholestasis. J Investing Med, 2002;50(3):193-200.
[7] Schaffner F, Scharnbeck HH, Hutterer F, et al. Mechanism of cholestasis. VII.a-Naphthylisothiocyanate-induced jaundice. Lab Invest. 1973;82:321-331.
[8] Krell H, Hoke H, Pfaff E. Development of intrahepatic cholestasis by a-Naphthylisothiocynate in rates. Gatroenterology. 1982;82:507-514.
[9] Connolly AK, Price SC, Connelly JC, et al. Early changes in bile duct lining cells and hepatocytes in rats treated with alpha-Naphthylisothioyanate. Toxicol Appl Pharmacol. 1988;93(2):208-219.
[10] Roth RA, Dahm LJ. Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate. Drug Metab Rev. 1997;29:153-165.
[11] Dietrich CG, Ottenhoff R, de Waart DR, et al. Role of MRP2 and GSH intrahepatic cycling of toxins. Toxicology. 2001;167:73-81.
[12] Jean PA, Bailie MB, Roth RA. 1-naphthylisothiocyanate-induced elevation of biliary glutathione. Biochem Pharmacol. 1995;49(2):197-202.
[13] Li MK, Crawford JM. The pathology of cholestasis. Semin Liver Dis. 2004;24(1):21-42.
[14] Santa Cruz V, Dugas TR, Kanz MF. Mitochondrial dysfunction occurs before transport or tight junction deficits in biliary epithelial cells exposed to bile from methylenedianiline-treated rats.Toxicol Sci. 2005;84(1):129-138.
[15] Roth RA, Dahm LJ. Neutrophil- and glutathione-mediated hepatotoxicity of alpha-naphthylisothiocyanate. Drug Metab Rev. 1997;29:153-165.
[16] Dahm LJ, Schultze AE, Roth RA. An antibody to neutrophils attenuates alpha-naphthylisothiocyanate-induced liver injury. J Pharmacol Exp Ther. 1991;256(1):412-420.
[17] Hill DA, Roth RA. Alpha-naphthylisothiocyanate causes neutrophils release factors that are cytotoxic to hepatocytes. Toxicol Appl Pharmacol. 1998;148(1):169-175.
[18] Hill DA, Jean PA, Roth RA. Bile duct epithelial cells exposed to alpha- naphthylisothiocyanate produce a factor that causes neutron-phil-dependent hepatocellular injury in vitro. Toxicol Sci. 1999;47:18-25.
[19] Kongo M, Ohta Y, Nishida K, et al. An association between lipid peroxidation and ANIT induced hepaticellar injury in vitro. Toxicol Lett. 1999;105:103-110.
[20] Ohta Y, Kongo M, Sasaki E, et al. Change in hepatic antioxidant defense system with liver injury development in rats with a single a-naphthy-lisothiocyanate intoxication. Toxiology. 1999;139:265-275.
[21] Ohta Y, Kongo M, Kishikawa T, et al. Preventive effect of melatonin on the progression of A-naphthylisothiocyanate-induced acute liver injury in rats. J Pineal Res. 2003;34:185-193.
[22]黄欣,黄志华.微生态制剂对肝内胆汁淤积性肝损伤兔模型胆汁和血清TNF-α和IL-6的影响.中国微生态学杂志,2003,15(3):137-140.
[23]刘凡,王晓东,黄志华.可溶性细胞间黏附分子在急性肝内胆汁淤积模型中的表达.实用儿科临床杂志,2006;21(19)1303-1304.
[24] Xu J, Lee G, Wang H, et al. Limited role for CXC chemokines in the pathogenesis of alpha--naphthylisothiocyanate-induced liver injury. Am. J. Physiol. Gastrointest. Liver Physiol. 2004;287:734-741.
[25] Kim ND, Moon JO, Slitt AL, et al. Early growth response factor-1 is critical for cholestatic liver injury. Toxicol Sci. 2006;90(2):586-595.
[26] Wong V. Phosphorylation of occludin correlates with occludin localization and function at the tight junction. Am J Physiol, 1997, 273(6 Pt 1): C1859-C1867.
[27] Harari Y, Weisbrodt NW, Moody FG. Ileal mucosal response to bacterial toxin challenge. J Trauma 2000;49: 306-313.
[28] Kiyono H, Kweon MN, Hiroi T, Takahashi I. The mucosal immune system: from specialized immune defense to infl ammation and allergy. Acta Odontol Scand 2001; 59: 145-153.
[29] Assimakopoulos SF , Vagianos CE , Pat soukis N , et al . Evidence for intestinal oxidative st ress in obst ructive jaundice2induced gut barrier dysfunction in rat s. Acta Physiol Scand , 2004 , 180 : 177-185.
[30]朱维铭,李宁.肠内营养[J].中国实用外科杂志,2001,21 (8):506-510.
[31]于晓明,金宏,糜漫天.肠屏障功能的损伤与营养素防护[J].解放军预防医学杂志,2006,24(1):74-76.
[32] Reynolds JV, Murchan P, Leonard N, et al. Gut barrier failure in experimental obstructive jaundice. J Surg Res,1996, 62:11-16.
[33] Sileri P, Morini S, Sica GS, et al. Bacterial translocation and intestinal morphological findings in jaundiced rats. Dig Dis Sci, 2002, 47: 929-934.
[34] Gencay C, Kilicoglu SS, Kismet K, et al. Effect of honey on bacterial translocation and intestinal morphology in obstructive jaundice. World J Gastroenterol, 2008, 14(21):3410-3415.
[35] Parks RW, Stuart Cameron CH, Gannon CD, et al. Changes in gastrointestinal morphology associated with obstructive jaundice. J Pathol, 2000, 192(6): 526-532.
[36]岳茂兴.胃肠道功能障碍及衰竭的诊断和治疗.世界华人消化杂志2002; 10: 3-6.
[37] Tsukita S, Furuse M, Itoh M. Multifunctional strands in tight junctions. Nat Rev Mol Cell Biol 2001;2: 285-293.
[38] Nusrat A, Parkos CA, Liang TW, Carnes DK, Madara JL. Neutrophil migration across model intestinal epithelia: monolayer disruption and subsequent events in epithelial repair. Gastroenterology 1997; 113: 1489-1500.
[39] Nusrat A, Turner JR, Madara JL. Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. Am J Physiol Gastrointest Liver Physiol 2000; 279: G851-857.
[40]宋红丽,吕飒,马力,李颖,刘沛. TNF-alpha影响肠黏膜上皮细胞间紧密连接蛋白的表达.世界华人消化杂志2004; 12: 1303-1306.
[41] Junichi L, Kazuaki U, Sachiko T, et al. Requirement of ZO-1 for the formation of belt-like adherens junctions during epithelial cell polarization[J]. J Cell Biology, 2007,176(6): 779-786.
[42] Matter Ka, Balda MS. Signaling to and from tight junctions[J]. Nat Rev Mol Cell Biol, 2003, 4(3): 225-236.
[43] Michael B, Fallon AR, Balda MS, et al. Altered hepatic localization and expression of occluding after common bile duct ligation. Am J Physiol, 1995, 269(38): 1057-1062.
[44] Assimakopoulos SF, Scopa CD, Charonis A, et al. Experimental obstructive jaundice disrupts intestinal mucosal barrier by altering occludin expression: beneficial effect of bombesin and neurotensin. J Am Coll Surg, 2004,198(5): 748-757.
[45]陈振勇,冯贤松,周有生.梗阻性黄疸大鼠肠黏膜上皮紧密连接蛋白和MLCK的研究.中国普通外科杂志, 2008,17(2): 140-144.
[46] Yang R, Harad T, Li J, et al . Bile modulates intestinal epithelial barrier function via an ext racellular signal related kinase 1/2 dependent mechanism. Intensive Care Med, 2005, 31(5):709-717.
[47] Portincasa P, Grattagliano I, Testini M, et al. Parallel intestinal and liver injury during early cholestasis in the rat: modulation by bile salts and antioxidants. Free Radic Biol Med, 2007, 42: 1381-1391.
[48] Bemelmans MH, Gouma DJ, Greve JW, et al. Cytokines tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice. Hepatology, 1992, 15:1132-1136.
[49] Schmitz H, Fromm M, Bentzel CJ, et al. Tumor necrosis factor-alpha(TNFalpha) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. J Cell Sci, 1999, 112:137-146.
[50] Blikslager AT, Roberts MC. Nitric oxide and the intestinal epithelial barrier: does it protect or damage the gut? J Pediar Gastroenterol Nutr, 1997, 25: 439-440.
[51] Hiscott J, Kwon H, Genin P. Hostile takeovers: viral appropriation of the NF-kapppaB pathway. J Clin Invest,2001;107(2):143-151.
[52] DETHASE M, LIX, KARIN M. Kinase regulation in inflammatory response[J].Nature, 2000, 406 (27) : 267-268.
[53] NEISH A S, GEWIRTZA T, ZENG Hui, et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-aubiquitination[J]. Science,2000, 289: 1560-1563.
[54] Mankertz J, Tavalali S, Schmitz H, et al. Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci, 2000, 113:2085-2090.
[55] McCarthy KM, Skare IB, Stankewich MC,et al. Occludin is a functional component of the tight junction. J Cell Sci. 1996,109:2287-2298.
[56] Han X, Fink MP, Delude RL. Proinflammatory cytokines cause NO-dependent and–independent changes in expression and lacalization of tight junction proteins in intestinal epithelial cells. Shock. 2003,19(3):229-237.
[57] Sappington PL, Han X, Yang R, et al. Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated caco-2 enterocytic monolayers. J Pharmacol Exp Ther. 2003,304(1):464-476.
[58] Fasano A, Fiorentini C, Donelli G, et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization in vitro. J Clin Invest,1995, 96(6):710-720.
[59] Nakajima Y, Baudry N, Duranteau J, et al. Microcirculation in intestinal villi: a comparison between hemorrhagic and endotoxin shock. Am J Respir Crit Care Med, 2001, 164:1526-1530.
[60] Tsukamoto T, Nigam SK. Role of tyrosine phosphorylation in the reassembly of occludin and other tight junction proteins. Am J Physiol, 1999, 276: F737-F750.
[61] Wells CL, Jechorek RP, Erlandsen SL. Inhibitory effect of bile on bacterial invasion of enterocytes: possible mechanism for increased translocation associated with obstructive jaundice. Crit Care Med, 1995, 23: 301-307.
[62] Simonovic I, Rosenberg J, Koutsouris A, et al. Enteropathogenic Escherichia coil dephosphorylates and dissociates occludin from intestinal epithelial tight junctions.Cell Microbiol, 2000, 2: 305-315
[63] Assimakopoulos SF, Thomopoulos KC, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest, 2006,36: 181-187.
[64] Sakaguchi S, Furusawa S, Yokota K, et al. The enhancing effect of tumour necrosis factor alpha on oxidative stress in endotoxemia. Pharmacol Toxicol, 1996, 79: 259-265.
[65] Pata C, Caglikulekci M, Cinel L, et al. The effects of antithrombin-III on inducible nitric oxide synthesis in experimental obstructive jaundice. Pharmacol Res, 2002, 46:325-331.
[66] Tsuji K, Kubota Y, Yamamoto S, et al. Increased neutrophil chemotaxis in obstructive jaundice: an in vitro experiment in rats. J Gastroenterol Hepatol, 1999, 14: 457-463.
[67] Tsai LY, Lee KT, Lu FJ. Biochemical events associated with ligation of the common bile duct in Wistar rats. J Formos Med Assoc, 1997, 96: 17-22.
[68] Rao RK, Basuroy S, Rao VU, et al.Tyrosine phosphorylation and dissociation of occludin, ZO-1 and E-cadherin-beta-catenin complexes form the cytoskeleton by oxidative stress. Biochem J, 2002, 368: 471-481.
[69] Assimakopoulos SF, Scopa CD, Zervoudakis G, et al. Bombesin and neurotensin reduce endotoxemia, intestinal oxidative stress, and apoptosis in experimental obstructive jaundice. Ann Surg, 2005, 241: 159-167.
[70] Rinne M, Kallimaki M,Arvilommi H,et al.Effect of probiotics and breastfeeding on the bifidobacterium and lactobacillus/enterococcus microbiota and humoral immune responses[J].J Pediatr,2005,147(2):186-191.
[71] Gill H S,Rutherfurd K J,Cross M L.Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes[J].J Clin Immunol,2001,21(4):264-271.
[72] Fujihashi K, Dohi T, Rennert PD et al. Peyer,s patches are required for oral toleranceto proteins[J]. Pnas, 2001, 98(6):3310-3315.
[73] Baia P, Ouyang Q, Xiao X R, et al. Probiotics modulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis [J].J Appl Microbiol, 2004,97(1):29-37.
[74] Andrew S. Neish, Andrew T. Gewirtz, Hui Zeng, et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-a ubiquitination. Science. 2000, 289:1560- 1563.
[75]周长玉,王江滨.益生菌治疗炎症性肠病的研究进展[J].国外医学消化系疾病分册,2004,24(3):172-174.
[76] Ewaschuk J B, Backer J L, Churchill T A, et al. Surface expression of Toll-like receptor 9 is up regulated on intestinal epithelial cells in response to pathogenic bacterial DNA[J].Infect Immun,2007,75(5):2572-2579.
[77] Resta-lenert S,Barrett K E.Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli(EIEC)[J]. Gut,2003,52(7): 988-997.
[78] Korzenik J R,Podolsky D K.Evolving knowledge and therapy of inflammatory bowel disease[J].Nat Rev Drug Discov,2006,5(3):197-209.
[79] Van Gossum A,Dewit O,Louis E,et al.Multicenter randomized controlled clinical trial of probiotics (Lactobacillus johnsonii,LA1) on early endoscop ic recurrence of Crohn′s disease after ileo-caecal resection[J].Inflamm Bowel Dis,2007,13(2):135- 142.
[80] Ko J S, Yang H R, Chang J Y, et al. Lactobacillus plantarum inhibits ep- ithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-alpha[ J ]. World J Gastroenterol, 2007, 13 (13) :1962-1975.
[81] Zyrek AA, Cichon C, Helms S, et al. Molecular mechanisms underlying the probiotic effects of Escherichia coli Nissle 1917 involve ZO-2 and PKCzeta redistribution resulting in tight junction and epithelial barrier repair. Cell Microbiol.2007,9(3):804-816.
[82] Madsen K, Cornish A, Soper P, et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function[J]. Gastroenterology,2001,121:(3) 580-591.
[83] Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of infection with enteroinvasive Escherichia coli(EIEC)[J].Gut, 2003,52 (7):988-997.
[84]王斌,但国蓉,等.乳杆菌黏附抑制致病性大肠杆菌对肠上皮样细胞侵袭的初步研究[ J ].解放军医学杂志, 2006, 31 (6):550-552.
[85]胡玉莲,黄志华,王晓东.双歧三联活菌片对淤胆幼鼠移行性肌电复合波影响及其干预胆汁淤积机制探讨[J].实用儿科临床杂志,2007,22(19):1487-1489.
[86] Neish A S, GewirtzAT, Zeng H, et al. Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination[J].Science,2000,289 (5484):1560-1563.
[87] Bai A P, Ouyang Q, Xiao X R, et al. Probioticsmodulate inflammatory cytokine secretion from inflamed mucosa in active ulcerative colitis[J]. International Journal of Clinical Practice, 2006, 60(3):284-288.
[88] Kim Y G, Ohta T, Takahashi T, et al. Probiotic Lactobacillus casei activates innate immunity via NF-kappaB and p38 MAP kinase signaling pathways[J].Microbes & Infection, 2006, 8 (4):994-1005.
[89] Madsen K L, Doyle J S, Jewell L D, et al. Lactobacillus species prevents colitis in interleukin 10 gene2deficient mice [J]. Gastroenterology, 1999,116(5):1107-1114.
[90] Ko J S, Yang H R, Chang J Y, et al. Lactobacillus plantarum inhibits epithelial barrier dysfunction and interleukin-8 secretion induced by tumor necrosis factor-alpha[ J ]. World J Gastroenterol, 2007,13(13):1962-1975.
[91] Bruewer M, Luegering A, Kucharzik T, et al. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms[J]. J Immunol, 2003, 171 (11):6164-6172.
[92] Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinalepithelial cells[J]. J Biol Chem, 2002, 277(52):50959-50965.
[93] Borruel N, CarolM, Casellas F, et al. Increased mucosal tumour necrosis factor alpha production in Crohn’s disease can be down-regulated ex vivo by probiotic bacteria [ J ]. Gut, 2002, 51(5):659-664.
[94] Carol M, Borruel N, Antolin M, et al. Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn’s disease[J]. Journal of Leukocyte Biology, 2006,79(5):917-922.
[95] Dubuquoy L, Jansson EA, Deeb S, et al. Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis[ J ]. Gastroenterology, 2003, 124(5):1265-1276.
[96] Kelly D, Campbell J I, King TP, et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytop lasmic shuttling of PPAR-gamma and RelA [ J ]. Nature Immunology, 2004, 5(1):104-112.
[97] Carmen Collado M, Jussi M, Seppo S. In vitro analysis of probiotic strain combinations to inhibit pathogen adhesion to human intestinalmucus[J].Food Res Intern,2007,40(5):629-636.
[98] Park J H, Umj I, Lee B J, et al. Encapsulated bifidobcterium bifidum potentiates intestinal IgA production[J].Cell Immunol,2002,219(1):22-27.
[99] Gionchetti P,Rizzello F,Helwigu,et al.Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial[J].Gastroenterology, 2003,124(5): 1202-1209.
[1] Liboni KC, Li N, Scumpia PO, Neu J. Glutamine modulates LPS-induced IL-8 production through IkappaB/NF-kappaB in human fetal and adult intestinal epithelium. J Nutr 2005; 135: 245-251.
[2]马涛,尤胜义.淋巴细胞凋亡,免疫抑制和脓毒症.国外医学?外科学分册2005; 32: 35-38.
[3]杨书良,李兰梅,陈育民.肠黏膜屏障的构成与功能研究进展.临床荟萃2008; 23: 1809-1811.
[4] Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut 2006; 55: 1512-1520.
[5] Barrett KE. New ways of thinking about (and teaching about) intestinal epithelial function. Adv Physiol Educ 2008; 32: 25-34.
[6] Deitch EA. Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings? Surgery 2002; 131:241-244.
[7]黎介寿.肠衰竭-概念:营养支持与肠黏膜屏障维护.肠外与肠内营养2004;11: 65-67.
[8] Walser EM, Nealon WH, Marroquin S, Raza S, Hernandez JA, Vasek J. Sterile fluid collections in acute pancreatitis: catheter drainage versus simple aspiration. Cardiovasc Intervent Radiol 2006; 29:102-107.
[9]刘春峰,袁壮.内脏缺血缺氧代谢障碍在SIRS和MODS中的作用[J ] .小儿急救医学,2000 ,7 (4) :180-182.
[10] Secchi A ,Ortanderl JM ,Schmidt W, et al . Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats [J] . J Surg Res ,2000 ,89 (1):26-30.
[11] Boros M , Takaichi S , Hatanaka K. Ischemic time-dependent microvascular changes and reperfusion injury in the rat small intestine[J].J Surg Res,1995,59 (2):311-320.
[12] Mitsuoka H ,Schmid2Schonbein GW. Mechanisms for blockade of in vivo activator production in the ischemic intestine and multiorgan failure[J].S hock ,2000 ,14 (5):522-527.
[13]张嘉,刘瑞林,刘牧林.肠道屏障功能损伤机制的研究进展.蚌埠医学院学报2005; 30: 277-279.
[14]刘晓臣,彭燕.肠屏障功能障碍与重症急性胰腺炎.世界华人消化杂志2006; 14: 3131-3135.
[15] Vallance BA, Dijkstra G, Qiu B, van der Waaij LA, van Goor H, Jansen PL, Mashimo H, Collins SM. Relative contributions of NOS isoforms during experimental colitis: endothelial-derived NOS maintains mucosal integrity. Am J Physiol Gastrointest Liver Physiol 2004; 287: G865-G74.
[16]王嘉川.内毒素血症在重症肝炎发病中的作用.寄生虫与感染性疾病2006; 4: 40-41.
[17]高金生,时志民,韩转叶,李校天,杨书良.肝硬化肠黏膜屏障损伤患者血浆D-乳酸、二胺氧化酶及内毒素的变化.临床荟萃2009; 24: 219-221.
[18]蒋朱明,于康.肠黏膜屏障损害与肠外和肠内营养[J].外科理论与实践,2000,5 (1) ;54-56.
[19] De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients:effect of glutamine. Crit Care Med 2005; 33:1125-1135.
[20] Singleton KD, Wischmeyer PE. Oral glutamine enhances heat shock protein expression and improves survival following hyperthermia. Shock 2006; 25: 295-299.
[21] Ikeda H, Suzuki Y, Suzuki M , et al . Apoptosis is a major mode of cell death caused by ischaemia and ischaemia/ reperfusion injury to the rat intestinal epithelium[J ] . Gut ,1998 ,42 (4) :530-537.
[22]王兴鹏,王冰娴,吴恺,等.细胞凋亡在急性坏死型胰腺炎早期肠黏膜上皮细胞死亡中的作用[J ] .中华消化杂志,2001 ,21(5):267-270.
[23]周德俊,王鹏志,朱理玮,等. Bcl22基因在供体小肠缺血再灌注损伤中作用的实验研究[J ] .中华普通外科杂志,1999 ,14(1):76-77.
[24] Hawrelak JA, Myers SP. The causes of intestinal dysbiosis: a review. Altern Med Rev 2004; 9: 180-197.
[25] Kanauchi O, Mitsuyama K, Araki Y, Andoh A.Modification of intestinal flora in the treatment of inflammatory bowel disease. Curr Pharm Des 2003; 9:333-346.
[26] Sartor RB. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics.Gastroenterology 2004; 126: 1620-1633.
[27] Dotan I, Rachmilewitz D. Probiotics in inflammatory bowel disease: possible mechanisms of action. Curr Opin Gastroenterol 2005; 21: 426-430.
[28]李兰娟.感染与微生态学.第1版.北京:人民卫生出版社, 2002: 295-300.
[29] Lewis K, Caldwell J, Phan V, et al. Decreased epithelial barrier function evoked by exposure to metabolic stress and nonpathogenic E. coli is enhanced by TNF-alpha.Am J Physiol Gastrointest Liver Physiol 2008; 294:G669-G678.
[30]白爱平.炎症性肠病肠黏膜屏障损伤机制.世界华人消化杂志2008; 16: 3187- 3191.
[31]何新颖,唐志鹏,张亚丽.肠上皮屏障与炎症性肠病研究进展.世界华人消化杂志2008; 16: 3316-3320.
[32] [32] Hoyt DB ,J unger WG,Loomis WH , et al . Effects of trauma on immune cell function : Impairment of intracellular calcium signaling[J ].S hock ,1994,2 (1):23-28.
[33]于勇,盛志勇,田惠民,等.大鼠烫伤后肠道免疫屏障损伤的实验研究[J ] .中华整形烧伤外科杂志,1996 ,12 (2) :86-89.
[34] Chen LW,Hsu CM ,Huang J K, et al . Effects of bombesin on gut mucosal immunity in rats after thermal injury[J ]. J Formos Med Assoc,2000 ,99 (6):491-498.
[35] Wang X , Andersson R. Soltesz V , et al . Gut origin sepsis, Macrophage function ,and oxygen extraction associated with acute pancreatitis in the rat [J ].World J Surg, 1996, 20 (3):299-308.
[36]陈意生,史景泉.多器官功能障碍综合征的病理基础[J].创伤外科杂志,2001,3 (1):72-74.
[37]陈德昌.多器官功能障碍综合征[A].见:吴阶平,裘法祖主编.黄家驷外科学[M].第6版.北京:人民卫生出版社,2000 :400-429.
[1] Vining DJ,Gelfand DW,Bechtold RE,et al.Technical feasibility of colon imaging with helical CT and virtual reality.AJR,1994,162:104-118.
[2]李子平,许达生,孟悛非,等.CT仿真内窥镜成像技术临床应用的初步探讨.中华放射学杂志,1998,32:104-107.
[3]张镭,瞿晓力,李杰,等.CT仿真结肠内窥镜的临床应用研究.中华放射学杂志,1999,33:171-174.
[4] Sudha Anupindi,James Perumpillichira,Esther J,et al. Low-dose CT colonography in children:initial experience,technical feasibility,and utility.Pediatr Radiol, 2005, 35:518-524.
[5] Capu?ay CM, Carrascosa PM, Bou-Khair A,Low radiation dose multislice CT colonography in children: Experience after 100 studies. Eur J Radiol.2005 56(3): 398-402.
[6] Hara AK,Johnson CD,MacCarty RL,et al. Incidental extracolonic findings at CT colonography. Radiology,2000,215(2):353-357.
[7] Hara AK,Johnson CD,MacCarty RL,et al. CT colonography: single- versus multi-detector row imaging. Radiology,2001,219(2):461-465.
[8] Fenlon HM,Nunes DP,Schroy PC 3rd,et al. A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med,1999,341(20): 1496-1503.
[9] Fletcher JG,Johnson CD,Welch TJ,et al. Optimization of CT colonography technique: prospective trial in 180 patients. Radiology,2000,216(3):704-711.
[10] Yee J,Akerbar GA,Hung RK,et al.Characteristics of CT colonography for the detection of colorectal neoplasia in 300 patients.Radiology,2001,219:685.
[11] Laghi A,Iannaccone R,Carbone I, et al.Multislice spiral CT colonography for the detection of colorectal polyps and neoplasms.Radiology,2001,221:307.
[12] Fenlon HM, McAneny DB,Nunes DP,et al. Occlusive colon carcinoma: virtual colonoscopy in the preoperative evaluation of the proximal colon. Radiology,1999,210(2):423-428.
[13] Royster AP,Fenlon HM,Clarke PD,et al. CT colonoscopy of colorectal neoplasms: two-dimensional and three-dimensional virtual-reality techniques with colonoscopic correlation.AJR Am J Roentqenol,1997,169(5):1237-1242.
[14]余深平,李子平,许达生,等.大肠充气螺旋CT扫描图像后处理功能的临床应用[J].中华放射学杂志,2000,34(5):295-299.
[15]张晓鹏,徐刚,徐舟,等.胃肠道螺旋CT三维成像方法及临床应用评价[J] .中华放射学杂志,2000,34(5):308-312.
[16] Carrascosa P, Capunay C, Bou-Khair A,et al.Virtual colonoscopy:is it a useful method in pediatrics? First experience (abstr).Eur Radiol,2001 (Supplement 1):322.
[17]翟晓力,张镭,翟仁友,等. CT结肠造影技术的临床初步应用—并与双对比钡灌肠对照[J].中华放射学杂志,2000,34(5):300-303.
[18] Chung DJ,Huh KC,Choi WJ,et al.CT colonography using 16-MDCT in the evaluation of colorectal cancer.Am J Roentgenol,2005,184(1):98-103.
[19] Dachman AH, Zalis ME. Quality and consistency in CT colonography and research reporting.Radiology 2004,230:319-323.
[20] Cotton PB, Durkalski VL, Pineau BC, et al. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA 2004,291(14):1713-1719.
[21] Luo MY, Shan H, Yao LQ, et al. Postprocessing techniques of CT colonography in detection of colorectal carcinoma. World J Gastroenterol 2004,10(11):1574-1577.
[22] Pickhardt PJ, Choi JR, Hwang I, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med 2003,349:2191- 2200.
[23] Carrascosa P, Capunay C, Castiglioni R, et al. Virtual colonoscopy. Experience in 500 patients. Acta Gastroenterol Latinoam 2003,33(3):145-149.
[24]许达生,余深平.进一步提高结肠CT仿真内窥镜的诊断水平[J ].中华放射学杂志,2000,34(5):293-294.