Effect of External Biliary Drainages on Tight Junctions of Intestinal Epithelia in Rats with Obstructive Jaundice_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Zhenyong , FENG Xiansong , YANG Peng , ZHOU Yousheng

Department of General Surgery, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China;

Corresponding author：

Keywords：

Obstructive jaundice; Bile; Intestinal mucosal barrier; Zona occludens-1; Occludin

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Objective To investigate the effects and mechanisms of bile on small intestine mucosal barrier.
Methods Fifty Wistar rats were assinged into 3 groups randomly: obstructive jaundice (OJ) group （n=20）, biliary external drainage group （n=20） and control group （n=10）. Ten days after operation, the plasma endotoxin level was determinated, the terminal ileum mucosas was obtained to be morphologically measured by light microscope, and immunohistochemistry and Western blot were uesd to examine the expressions of tight junction proteins zona occludens-1 (ZO-1) and occludin in the mucosas.
Results Atrophy significantly appeared in the distal ileum mucosas in OJ group. Compared with control group, the intestinal villus height, mucosa thickness and crypt depth in OJ group were obviously decreased 27.8%, 21.7%, and 25.4% (P=0.001, 0.001, 0.040). There were no differences between external drainage group and control group (P=0.050, 0.070, 0.080); While the values of external drainage group were significantly higher than those in OJ group (all P=0.001). The level of plasma endotoxin was up to (1.49±0.27) EU/ml in OJ group compared with control group 〔（0.27±0.09） EU/ml〕, P=0.001. In external drainage group, the value was （0.91±0.25） EU/ml, which was obviously higher than that in control group and lower than that in OJ group （all P=0.001）. Immunohistochemical study showed b positive expression of ZO-1 dropped from 7/10 in the control group to 6/20 in OJ group （P=0.040）, occludin expression was 8/10 in control group and 7/20 in OJ Group （P=0.020）; expressions of them in external drainage group 〔8/20 （P=0.100,0.210） and 9/20 （P=0.060, 0.200）〕 displayed no significant differences compared with the other twogroups. Quantitative testing of Western blot showed the expressions of ZO-1 and occludin in OJ group were significantly lower than those in control group (P=0.001, 0.010), the values in external drainage group were higher than those in OJ group （P=0.005, 0.014）. The expression of ZO-1 was lower in external drainage group than that in control group (P=0.001), and there was no significant difference of occludin between the two groups (P=0.062）.
Conclusion Lack of intestinal bile will undermine the intestinal tight junction protein composition, and make intestinal mucosal barrier impaired. The intestinal barrier more severely injured when biliary tract obstructs because of multiple factors. Bile plays an important role in the maintenance of intestinal mucosal barrier.

Citation： CHEN Zhenyong,FENG Xiansong,YANG Peng,ZHOU Yousheng. Effect of External Biliary Drainages on Tight Junctions of Intestinal Epithelia in Rats with Obstructive Jaundice. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(5): 454-458. doi: Copy

1.	Sano T, Ajiki T, Takeyama Y, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats [Ｊ]. Surgery, 2004; 136(3): 693-699.
2.	姜宪，姜旭，申蓉硕，等. 梗阻性黄疸大鼠血液中内毒素含量与组织形态学变化 [Ｊ]. 延边大学医学学报, 2006; 29(1): 16-19.
3.	Ogata Y, Nishi M, Nakayama H, et al. Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats [Ｊ]. J Surg Res, 2003; 115(1): 18-23.
4.	Assimakopoulos SF, Vagianos CE, Charonis A, et al. Intestinal failure in obstructive jaundice [Ｊ]. World J Gastroenterol, 2005; 11(24): 3806-3807.
5.	崔红元, 韦军民, 朱明炜. 梗阻性黄疸肠黏膜屏障损伤的研究现状 [Ｊ]. 中国临床营养杂志, 2007; 15(4): 242-246.
6.	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 [Ｊ]. 中国普通外科杂志, 2008; 17(2): 140-144.
7.	Sheen-Chen SM, Chen HS, Ho HT, et al. Effect of bile acid replacement on endotoxin-induced tumor necrosis factor-alpha production in obstructive jaundice [Ｊ]. World J Surg, 2002; 26(4): 448-450.
8.	Assimakopoulos SF, Scopa CD, Vagianos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice [Ｊ]. World J Gastroenterol, 2007; 13(48): 6458-6464.
9.	González-Mariscal L, Tapia R, Chamorro D. Crosstalk of tight junction components with signaling pathways [Ｊ]. Biochim Biophys Acta, 2008; 1778(3): 729-756.
10.	巩义春, 李闻. 胆汁内外引流术对梗阻性黄疸大鼠血内毒素、IL-2及IL-6的影响 [Ｊ]. 胃肠病学和肝病学杂志, 2008; 17(4): 329-331.
11.	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]. J Am Coll Surg, 2004; 198(5): 748-757.
12.	刘金钢, 那延立, 郭宏斌, 等. 生长激素减轻梗阻性黄疸时肠菌及内毒素移位的实验研究 [Ｊ]. 中国普外基础与临床杂志, 2002; 9(3): 172-174.
13.	Scopa CD, Koureleas S, Tsamandas AC, et al. Beneficial effects of growth hormone and insulin-like growth factor Ⅰ on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats [Ｊ]. J Am Coll Surg, 2000; 190(4): 423-431.
14.	刘国平, 周文平, 朱闻溪, 等. L-精氨酸对梗阻性黄疸大鼠肠道屏障的保护作用 [Ｊ]. 肝胆外科杂志, 2003; 11(2): 153-154, 152.
15.	田延锋, 李勇. 梗阻性黄疸对肠黏膜屏障功能的影响及药物干预 [Ｊ]. 河北医科大学学报, 2007; 28(2): 151-154.
16.	Margaritis VG, Filos KS, Michalaki MA, et al. Effect of oral glutamine administration on bacterial tanslocation, endotoxemia, liver and ileal morphology, and apoptosis in rats with obstructive jaundice [Ｊ]. World J Surg, 2005; 29(10): 1329-1334.
17.	张小明, 寇治民, 康二虎, 等. 褪黑素对大鼠梗阻性黄疸肾损害的保护作用 [Ｊ]. 中国普外基础与临床杂志, 2005; 12(1): 55-58.
18.	陈振勇, 冯贤松, 周有生, 等. 胆汁对梗阻性黄疸大鼠小肠上皮紧密连接的调控 [Ｊ]. 中国普通外科杂志, 2008; 17(8)： 760-763.

1. Sano T, Ajiki T, Takeyama Y, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats [Ｊ]. Surgery, 2004; 136(3): 693-699.
2. 姜宪，姜旭，申蓉硕，等. 梗阻性黄疸大鼠血液中内毒素含量与组织形态学变化 [Ｊ]. 延边大学医学学报, 2006; 29(1): 16-19.
3. Ogata Y, Nishi M, Nakayama H, et al. Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats [Ｊ]. J Surg Res, 2003; 115(1): 18-23.
4. Assimakopoulos SF, Vagianos CE, Charonis A, et al. Intestinal failure in obstructive jaundice [Ｊ]. World J Gastroenterol, 2005; 11(24): 3806-3807.
5. 崔红元, 韦军民, 朱明炜. 梗阻性黄疸肠黏膜屏障损伤的研究现状 [Ｊ]. 中国临床营养杂志, 2007; 15(4): 242-246.
6. 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 [Ｊ]. 中国普通外科杂志, 2008; 17(2): 140-144.
7. Sheen-Chen SM, Chen HS, Ho HT, et al. Effect of bile acid replacement on endotoxin-induced tumor necrosis factor-alpha production in obstructive jaundice [Ｊ]. World J Surg, 2002; 26(4): 448-450.
8. Assimakopoulos SF, Scopa CD, Vagianos CE. Pathophysiology of increased intestinal permeability in obstructive jaundice [Ｊ]. World J Gastroenterol, 2007; 13(48): 6458-6464.
9. González-Mariscal L, Tapia R, Chamorro D. Crosstalk of tight junction components with signaling pathways [Ｊ]. Biochim Biophys Acta, 2008; 1778(3): 729-756.
10. 巩义春, 李闻. 胆汁内外引流术对梗阻性黄疸大鼠血内毒素、IL-2及IL-6的影响 [Ｊ]. 胃肠病学和肝病学杂志, 2008; 17(4): 329-331.
11. 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]. J Am Coll Surg, 2004; 198(5): 748-757.
12. 刘金钢, 那延立, 郭宏斌, 等. 生长激素减轻梗阻性黄疸时肠菌及内毒素移位的实验研究 [Ｊ]. 中国普外基础与临床杂志, 2002; 9(3): 172-174.
13. Scopa CD, Koureleas S, Tsamandas AC, et al. Beneficial effects of growth hormone and insulin-like growth factor Ⅰ on intestinal bacterial translocation, endotoxemia, and apoptosis in experimentally jaundiced rats [Ｊ]. J Am Coll Surg, 2000; 190(4): 423-431.
14. 刘国平, 周文平, 朱闻溪, 等. L-精氨酸对梗阻性黄疸大鼠肠道屏障的保护作用 [Ｊ]. 肝胆外科杂志, 2003; 11(2): 153-154, 152.
15. 田延锋, 李勇. 梗阻性黄疸对肠黏膜屏障功能的影响及药物干预 [Ｊ]. 河北医科大学学报, 2007; 28(2): 151-154.
16. Margaritis VG, Filos KS, Michalaki MA, et al. Effect of oral glutamine administration on bacterial tanslocation, endotoxemia, liver and ileal morphology, and apoptosis in rats with obstructive jaundice [Ｊ]. World J Surg, 2005; 29(10): 1329-1334.
17. 张小明, 寇治民, 康二虎, 等. 褪黑素对大鼠梗阻性黄疸肾损害的保护作用 [Ｊ]. 中国普外基础与临床杂志, 2005; 12(1): 55-58.
18. 陈振勇, 冯贤松, 周有生, 等. 胆汁对梗阻性黄疸大鼠小肠上皮紧密连接的调控 [Ｊ]. 中国普通外科杂志, 2008; 17(8)： 760-763.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of External Biliary Drainages on Tight Junctions of Intestinal Epithelia in Rats with Obstructive Jaundice

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