Experiment Study of The Anti-Oxidative Treatment in Biliary Tract with Pancreaticobiliary Maljunction_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CHEN Feng ¹ , TANG Lin ² , WANG Jian ³ , HUANG Shungen ³ , WANG Xingdong ³

1.Department of General Surgery， Shanghai 6th People’s Hospital， Shanghai 200233， China;;
2. The Academy of Basic Medicine， Nanjing University of Chinese Medicine， Nanjing 210046， Jiangsu Province， China;;
3. Department of General Surgery， Children Hospital Affiliated to Soochow University， Suzhou 215003， Jiangsu Province， China;

Corresponding author：

Keywords：

Pancreaticobiliary maljunction; Biliary tract injury; Animal model; Anti-oxidative; Melatonin

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Objective 　To evaluate the efficacy of anti-oxidative treatment in cats with pancreaticobiliary maljunction.
Methods 　Thirteen healthy cats as control group were made a model that resembling the common channel of pancreaticobiliary maljunction as in humans，and were divided randomly into two groups：7 cats in untreated group were not treated，6 cats in anti-oxidative group were treated with melatonin，vitamin C， and vitamin E. Six months later， the gallbladders of these animals were removed and histopathological changes were evaluated by pathological and electron microscopic examination. The level of MDA，amylase concentration in the gallbladder bile，and percentage of proliferating cell nuclear antigen （PNCA） positive cells were also test.
Results 　All cats had survived for 6 months after operation. The wall of gallbladder and the bile became thicker in untreated group than that in normal control group， and there were no significant differences between untreated group and anti-oxidative group. The gallbladder epithelium became villous in appearance in untreated group，although the epithelium of that in normal control group was flat with few folds. The epithelial cells of gallbladder arranged tightly in normal control group， while a significant change such as endoplasmic reticulum expanding， intercellular space broadening， and cellular nucleus deforming were observed in untreated group. The things in anti-oxidative group were better than untreated group. The amylase concentration in the gallbladder bile was （203.02±65.04）U in normal control group，（9 368.09±2 204.42） U in untreated group， and
（8 746.25±2 077.95） U in anti-oxidative group， respectively. The amylase concentration in untreated group and anti-oxidative group were higher than that in normal control group （P=0.003），and there was no significant difference between the untreated group and anti-oxidative group （P=0.642）. The percentage of PNCA positive cells was （7.29±2.70）% in normal control group，（54.71±10.90）% in untreated group, and （48.17±13.06）% in anti-oxidative group， respectively （F=48.11，P=0.001），and the percentage of PNCA positive cells in untreated group was higher than that in anti-oxidative group （P=0.001）. The level of MDA was （1.095±0.653） nmol/mg prot in normal control group，（2.745±1.533） nmol/mg prot in untreated group, and （1.302±0.771） nmol/mg prot in anti-oxidative group， respectively （F=5.17，P=0.017）, and the level of MDA in untreated group was higher than that in anti-oxidative group （P=0.017）.
Conclusion 　The anti-oxidative treatment is effective to pancreaticobiliary maljunction.

Citation： CHEN Feng,TANG Lin,WANG Jian,HUANG Shungen,WANG Xingdong. Experiment Study of The Anti-Oxidative Treatment in Biliary Tract with Pancreaticobiliary Maljunction. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(10): 1069-1073. doi: Copy

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15.	Watanabe Y， Toki A， Todani T. Bile duct cancer developed after cyst excision for choledochal cyst[J]. J Hepatobiliary Pancreat Surg， 1999， 6(3)： 207-212.
16.	Kamisawa T， Okamoto A. Biliopancreatic and pancreatobiliary refluxes in cases with and without pancreaticobiliary maljunction：diagnosis and clinical implications[J]. Digestion， 2006， 73(4)： 228-236.
17.	Kamisawa T， Anjiki H， Egawa N， et al. Diagnosis and clinical implications of pancreatobiliary reflux[J]. World J Gastroenterol， 2008， 14(43)： 6622-6626.
18.	Kamisawa T， Takuma K， Anjiki H， et al. Pancreaticobiliary maljunction[J]. Clin Gastroenterol Hepatol， 2009， 7(11 Suppl)： S84-S88.
19.	Shibutani S， Takeshita M， Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG[J]. Nature， 1991， 349(6308)： 431-434.
20.	Thakor AS， Herrera EA， Serón-Ferré M， et al. Melatonin and vitamin C increase umbilical blood flow via nitric oxide-dependent mechanisms[J]. J Pineal Res， 2010， 49(4)： 399-406.
21.	Sharma MK， Buettner GR. Interaction of vitamin C and vitamin E during free radical stress in plasma：an ESR study[J]. Free Radic Biol Med， 1993， 14(6)： 649-653.
22.	Ames BN. Micronutrients prevent cancer and delay aging[J]. Toxicol Lett， 1998， 102(102-103)：5-18.
23.	Kirsh VA， Hayes RB， Mayne ST， et al. Supplemental and dietary vitamin E， beta-carotene， and vitamin C intakes and prostate cancer risk[J]. J Natl Cancer Inst， 2006， 98(4)： 245-254.
24.	Martínez-Cruz F， Osuna C， Guerrero JM. Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver：its prevention by melatonin， Vitamin E， and Vitamin C[J]. Neurosci Lett， 2006， 392(1-2)： 1-4.
25.	Factor VM， Laskowska D， Jensen MR， et al. Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model[J]. Proc Natl Acad Sci U S A， 2000， 97(5)： 2196-2201.

1. The Jananese Study Group on Pancreaticobiliary Maljunction（JSPBM）. Diagnostic criteria of pancreaticobiliary maljunction[J]. J Hep Bil Pancr Surg， 1994， 1(3)： 219-221.
2. 陈风，汪健，蒋晓飞，等. 急性胆源性胰腺炎和胰胆管合流异常的关系[J]. 肝胆胰外科杂志， 2009， 21(2)：98-100.
3. Kamisawa T， Tu Y， Nakajima H， et al. The presence of a common channel and associated pancreaticobiliary diseases：a prospective ERCP study[J]. Dig Liver Dis， 2007， 39(2)： 173-179.
4. Dowdy GS Jr， Waldron GW， Brown WG. Surgical anatomy of the pancreatobiliary ductal system. Observations[J]. Arch Surg， 1962， 84(4)：229-246.
5. 孟翔凌，何磊，徐阿曼. 等. 胰胆管合流异常的临床意义[J]. 中国普外基础与临床杂志， 2003， 10(5)：451-453.
6. Otani K， Shimizu S， Chijiiwa K， et al. Immunohistochemical detection of 8-hydroxy-2’-deoxyguanosine in gallbladder epithelium of patients with pancreaticobiliary maljunction[J]. Eur J Gastroenterol Hepatol， 2001， 13(11)： 1363-1369.
7. 何平，石景森，王作仁，等. 合并胰胆管合流异常时胆道疾病的手术选择[J]. 中国现代医学杂志， 2002， 12(6)： 105-106.
8. Seki M. Yanagisawa A. Ninomiya E. et al. Clinicopathology of pancreaticobiliary maljunction：relationship between alterations in background biliary epithelium and neoplastic development[J]. J Hepatobiliary Pancreat Surg， 2005， 12(3)： 254-262.
9. Kobayashi S， Ohnuma N， Yoshida H， et al. Preferable operative age of choledochal dilation types to prevent patients with pancreaticobiliary maljunction from developing biliary tract carcinogenesis[J]. Surgery， 2006， 139(1)： 33-38.
10. 陈风，吕毅，汪健，等. 胰胆管合流异常肝损伤的抗氧化治疗实验研究[J]. 肝胆胰外科杂志， 2011， 23(6)： 481-483.
11. Fumino S， Ono S， Kimura O， et al. Diagnostic impact of computed tomography cholangiography and magnetic resonance cholangiopancreatography on pancreaticobiliary maljunction[J]. J Pediatr Surg， 2011， 46(7)：1373-1378.
12. Kamisawa T， Takuma K， Itokawa F， et al. Endoscopic diagnosisof pancreaticobiliary maljunction[J]. World J GastrointestEndosc， 2011， 3(1)： 1-5.
13. Hori H， Ajiki T， Fujita T， et al. Double cancer of gall bladder and bile duct not associated with anomalous junction of the pancreaticobiliary duct system[J]. Jpn J Cli Oncol， 2006， 36(10)： 638-642.
14. 杨蕾，张斌，李长锋，等. 人胰胆管合流异常胆汁对胆管细胞的影响及其机理探讨[J]. 中国普外基础与临床杂志， 2007，14(6)： 648-651.
15. Watanabe Y， Toki A， Todani T. Bile duct cancer developed after cyst excision for choledochal cyst[J]. J Hepatobiliary Pancreat Surg， 1999， 6(3)： 207-212.
16. Kamisawa T， Okamoto A. Biliopancreatic and pancreatobiliary refluxes in cases with and without pancreaticobiliary maljunction：diagnosis and clinical implications[J]. Digestion， 2006， 73(4)： 228-236.
17. Kamisawa T， Anjiki H， Egawa N， et al. Diagnosis and clinical implications of pancreatobiliary reflux[J]. World J Gastroenterol， 2008， 14(43)： 6622-6626.
18. Kamisawa T， Takuma K， Anjiki H， et al. Pancreaticobiliary maljunction[J]. Clin Gastroenterol Hepatol， 2009， 7(11 Suppl)： S84-S88.
19. Shibutani S， Takeshita M， Grollman AP. Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG[J]. Nature， 1991， 349(6308)： 431-434.
20. Thakor AS， Herrera EA， Serón-Ferré M， et al. Melatonin and vitamin C increase umbilical blood flow via nitric oxide-dependent mechanisms[J]. J Pineal Res， 2010， 49(4)： 399-406.
21. Sharma MK， Buettner GR. Interaction of vitamin C and vitamin E during free radical stress in plasma：an ESR study[J]. Free Radic Biol Med， 1993， 14(6)： 649-653.
22. Ames BN. Micronutrients prevent cancer and delay aging[J]. Toxicol Lett， 1998， 102(102-103)：5-18.
23. Kirsh VA， Hayes RB， Mayne ST， et al. Supplemental and dietary vitamin E， beta-carotene， and vitamin C intakes and prostate cancer risk[J]. J Natl Cancer Inst， 2006， 98(4)： 245-254.
24. Martínez-Cruz F， Osuna C， Guerrero JM. Mitochondrial damage induced by fetal hyperphenylalaninemia in the rat brain and liver：its prevention by melatonin， Vitamin E， and Vitamin C[J]. Neurosci Lett， 2006， 392(1-2)： 1-4.
25. Factor VM， Laskowska D， Jensen MR， et al. Vitamin E reduces chromosomal damage and inhibits hepatic tumor formation in a transgenic mouse model[J]. Proc Natl Acad Sci U S A， 2000， 97(5)： 2196-2201.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Experiment Study of The Anti-Oxidative Treatment in Biliary Tract with Pancreaticobiliary Maljunction

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