内源性β—葡萄糖醛酸酶与原发性肝内胆管结石关系的研究
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摘要
目的：探讨内源性β—葡萄糖醛酸酶与原发性肝内胆管结石的关系。
方法：采用改良的Fishman方法测定原发性肝内胆管结石患者的胆汁及肝组织中内源性β—葡萄糖醛酸酶的活性。
结果：1．原发性肝内胆管结石患者结石侧胆管胆汁内源性β-G的活性明显高于对照组，而非结石侧胆管胆汁内源性β-G的活性与对照组无显著性差异。2．左肝结石患者的胆汁内源性β-G的活性左侧明显高于右侧，右肝结石患者的胆汁内源性β-G的活性右侧明显高于左侧，而左右肝同时有结石的患者左右侧胆汁内源性β-G的活性差别无显著性。3．左肝结石患者的肝组织内源性β-G的活性左侧明显高于右侧，右肝结石患者的肝组织内源性β-G的活性右侧明显高于左侧，而左右肝同时有结石的患者左右侧肝组织内源性β-G的活性差别无显著性。
结论：象外源性β-G一样，内源性β-G也可能参与原发性肝内胆管结石的成石过程。并且，原发性肝内胆管结石患者内源性β-G肝内分布存在差异，表现为结石侧内源性β-G较非结石侧明显升高，提示原发性肝内结石可能为肝
安徽医科大学硕士学位论文
内局限性病变，这为外科手术切肝治疗肝内胆管结石提供一定的理论基础。
Objective:To investigate the relationship between endogenous -glucuronidase( β-G) and the primary intrahepatic bile duct stone. Methods:The activity of endogenous β-G in bile and hepatic tissue from the paitents with the intrahepatic bile duct stone was measured by modified Fishman method..
Results:1 The activity of endogenous β-G in the bile from bile duct with intrahepatic bile duct stone was significantly higher than that of the control group,while the activity of endogenous β-G without intrahepatic bile duct stone was not significantly higher than that of the control group. 2 The activity of endogenous β-G in the bile of left hepatic duct with left intrahepatic bile duct stone was significantly higher than that of the right hepatic duct in the same patient, while right was significantly higher than that of the left when the patients with right intrahepatic bile duct stone. Meanwhile, it showed unsignificant difference between endogenous β-G activity of the bile from left intrahepatic bile duct and that of right intrahepatic bile duct. 3 The activity of endogenous β-G in the hepatic tissue of left hepatic duct from the patients with left intrahepatic bile duct stone was significantly higher than that of the right, while
the right was significantly higher than that of the left when the patients with right intrahepatic bile duct stone. Meanwhile, it showed unsignificant difference between endogenous β -G activity of the hepatic tissue from left hepatic tissue and that of right hepatic tissue.
Conclusions: Endogenous β-Glucuronidase( β -G) might be play a role in the formation of gallstone just as the exogenous β-Glucuronidase does. The activity of endogenous β -G was diference in different parts of the liver of the patients with intrahepatic bile duct stone.It showed that the activity of endogenous β -G with intrahepatic bile duct stone was significantly higher than that of the control group.It also hints that the formation of primary intrahepatic bile duct stone might be local pathological changes,which provided a rationale for the clinic to heal patients with intrahepatic bile duct stone with cutting part of the pathological liver.
方法：采用改良的Fishman方法测定原发性肝内胆管结石患者的胆汁及肝组织中内源性β—葡萄糖醛酸酶的活性。
结果：1．原发性肝内胆管结石患者结石侧胆管胆汁内源性β-G的活性明显高于对照组，而非结石侧胆管胆汁内源性β-G的活性与对照组无显著性差异。2．左肝结石患者的胆汁内源性β-G的活性左侧明显高于右侧，右肝结石患者的胆汁内源性β-G的活性右侧明显高于左侧，而左右肝同时有结石的患者左右侧胆汁内源性β-G的活性差别无显著性。3．左肝结石患者的肝组织内源性β-G的活性左侧明显高于右侧，右肝结石患者的肝组织内源性β-G的活性右侧明显高于左侧，而左右肝同时有结石的患者左右侧肝组织内源性β-G的活性差别无显著性。
结论：象外源性β-G一样，内源性β-G也可能参与原发性肝内胆管结石的成石过程。并且，原发性肝内胆管结石患者内源性β-G肝内分布存在差异，表现为结石侧内源性β-G较非结石侧明显升高，提示原发性肝内结石可能为肝
安徽医科大学硕士学位论文
内局限性病变，这为外科手术切肝治疗肝内胆管结石提供一定的理论基础。
Objective:To investigate the relationship between endogenous -glucuronidase( β-G) and the primary intrahepatic bile duct stone. Methods:The activity of endogenous β-G in bile and hepatic tissue from the paitents with the intrahepatic bile duct stone was measured by modified Fishman method..
Results:1 The activity of endogenous β-G in the bile from bile duct with intrahepatic bile duct stone was significantly higher than that of the control group,while the activity of endogenous β-G without intrahepatic bile duct stone was not significantly higher than that of the control group. 2 The activity of endogenous β-G in the bile of left hepatic duct with left intrahepatic bile duct stone was significantly higher than that of the right hepatic duct in the same patient, while right was significantly higher than that of the left when the patients with right intrahepatic bile duct stone. Meanwhile, it showed unsignificant difference between endogenous β-G activity of the bile from left intrahepatic bile duct and that of right intrahepatic bile duct. 3 The activity of endogenous β-G in the hepatic tissue of left hepatic duct from the patients with left intrahepatic bile duct stone was significantly higher than that of the right, while
the right was significantly higher than that of the left when the patients with right intrahepatic bile duct stone. Meanwhile, it showed unsignificant difference between endogenous β -G activity of the hepatic tissue from left hepatic tissue and that of right hepatic tissue.
Conclusions: Endogenous β-Glucuronidase( β -G) might be play a role in the formation of gallstone just as the exogenous β-Glucuronidase does. The activity of endogenous β -G was diference in different parts of the liver of the patients with intrahepatic bile duct stone.It showed that the activity of endogenous β -G with intrahepatic bile duct stone was significantly higher than that of the control group.It also hints that the formation of primary intrahepatic bile duct stone might be local pathological changes,which provided a rationale for the clinic to heal patients with intrahepatic bile duct stone with cutting part of the pathological liver.
引文
1. Ho KJ. Activation of human beta-glucuronidase by murine monoclonal antibodiesandbovineserumalbumininanuncompetitivefashion.Biochem Mol Biol Int 1995,36(6): 1277-1286
2．杨波，张弘，朱善德等。人肝组织内源性β-葡萄糖醛酸苷酶与胆红素结石关系的免疫电镜观察．中华医学杂志，1999，79(7)：513．
3. Ho KJ. Pathogenesis of the formation of pigment gallstones. The role of human biliary β—glucuronidase. Med Today, 1992, 159:694-697.
4．傅贤波，周孝思，张挽华，等。胆红素钙的沉淀过程及胆汁酸盐对其影响。中华外科杂志，1984，22(5)：266．
5. Maki T. Pathogenesis of calcium bilirubinate gallstones; role ofE coli β-glucuronidase and coagulation by inorganic ions polyelectrocyte and agitation(J).Ann Surg, 1966,164(1): 90.
6. Finch P J, Ryan FP, Rogers K. Gastric enzymes as a screening test for gastric cancer. Gut,1987;28:319.
7. Weidener, Semole JP, Welch WR, et al. Tumor angiogenesis and metastasis cerrelation in invasive breast carcinoma. N Engl J Med, 1991,324:1.
8. Ho KJ. A large scaled purification of β—glucuronidase from human liver by immunoaffinity chromatography. Boitech Applied Biochem, 1991, 14:296-298.
9. Bagshow KD. Antibody directed enzymes revive anti-cancer prodrugs concept[J]. Br J Cancer, 1987,56:531-534.
10. Ho KJ.. Studies on the effects of pH and bile acids in regard to human beta-glucuronidase role in the pathogenesis of cholelithiasis. Biochim Biophys Acta 1085, 827(3):197-206.
11. Osnes T, Sandstad O. beta-Glucuronidase in common duct bile, methodological aspects, variation of pH optima and relation to gallstones. cand J Clin Lab Invest, 1997,57(4):307-315.
12. Oyabu, et al. Nonbacterial transformation of bilirubin in bile. Dig Dis Sci, 1987,32:809-816.
13. Ho, KJ, Hsu SC. Chen JS, Ho LH. Human biliary beta-glucuronidase correlation of its activity with deconjugation of bilirubin in the bile. Eur J Clin Invest, 1986, 6(5):361-367.
14. Ho YC, Ho KJ. Measure of human beta-glucuronidas of its activity in gallbladder bile devoid of intrinsic interference. Dig Dis Sci, 1988,33(4)435-442.
15．黄志强，杨可贞，孟宪钧，等。胆汁β-葡萄糖醛酸酶活性的意义。中华外科杂志，1982，20(1)：49-52．
16．王宏林，郭仁宣，刘小芳，等。乙肝病毒感染者胆汁及血清内源性β-葡萄糖醛酸酶含量与胆红素结石的关系。中华肝胆外科杂志，2001，7(6)：346．
17. Masion A. Hepatitis B virus: replication in diverse cell types during chronic hepatitis B virus infection. Hepatology, 1993,18:781-789.
18. Heathcote EJ, Cauch-Dudek K, Walker V, et al. The Canadian multicenter double blind randomized controlled trial of ursodeoxycholic acid in primary biliary cirrosis. Hepatology, 1999,24:1149,
19. HO KJ. Development and opimization of an enyme-linked immunosorbent assay employing two murine monoclonal antibodies for absolute quantitation of human beta-glucuronidas.Biotech Applied Biochem, 1992,16:1-10.
20．赵青川，樊代明，李开宗，等。ELISA法观察组织源性β-G在原发性肝内胆管结石中的变化。中华肝胆外科杂志。1998，4(5)：25
21．李宁，肖路加，陈世玮，等。胆红素钙结石兔模型β-葡萄糖醛酸酶的变化。华西医科大学学报，1990，21(2)：185-187．
22．杨波，朱善德，杜晓炬，等。肝组织内源性β-葡萄糖醛酸酶与胆红素结石关系的免疫电镜研究．中华外科杂志2000，6(2)：123-125
23. Chen CY, Shiesh SC,Tsao HC, et al. Human biliary beta-glucuronidase activity before and after relief of bile duct obstruction: is it the major role in the formation of pigment gallstones? J Gastroenterol Hepatol. 2000, 15(9): 1071-1075.
24. Stewart L, Oesterle AL, Erdan I, et al. Pathogenesis of pigment gallstones in Western societies the central role of bacteria. J Gastrointest Surg, 2002, 6(6):891-903.
25. Chen CY, Shiesh SC, Lin XZ. Biliary sludge and pigment stone formation in bile duct-ligated guinea pigs. Dig Dis Sci, 1999,44(1):203-209.
26．陈锡谋，黄淑玉，叶惠华，等。非胆道疾病患者胆汁中β-葡萄糖醛酸酶活力测定及临床意义。中华消化杂志，1991，11：363．
2．杨波，张弘，朱善德等。人肝组织内源性β-葡萄糖醛酸苷酶与胆红素结石关系的免疫电镜观察．中华医学杂志，1999，79(7)：513．
3. Ho KJ. Pathogenesis of the formation of pigment gallstones. The role of human biliary β—glucuronidase. Med Today, 1992, 159:694-697.
4．傅贤波，周孝思，张挽华，等。胆红素钙的沉淀过程及胆汁酸盐对其影响。中华外科杂志，1984，22(5)：266．
5. Maki T. Pathogenesis of calcium bilirubinate gallstones; role ofE coli β-glucuronidase and coagulation by inorganic ions polyelectrocyte and agitation(J).Ann Surg, 1966,164(1): 90.
6. Finch P J, Ryan FP, Rogers K. Gastric enzymes as a screening test for gastric cancer. Gut,1987;28:319.
7. Weidener, Semole JP, Welch WR, et al. Tumor angiogenesis and metastasis cerrelation in invasive breast carcinoma. N Engl J Med, 1991,324:1.
8. Ho KJ. A large scaled purification of β—glucuronidase from human liver by immunoaffinity chromatography. Boitech Applied Biochem, 1991, 14:296-298.
9. Bagshow KD. Antibody directed enzymes revive anti-cancer prodrugs concept[J]. Br J Cancer, 1987,56:531-534.
10. Ho KJ.. Studies on the effects of pH and bile acids in regard to human beta-glucuronidase role in the pathogenesis of cholelithiasis. Biochim Biophys Acta 1085, 827(3):197-206.
11. Osnes T, Sandstad O. beta-Glucuronidase in common duct bile, methodological aspects, variation of pH optima and relation to gallstones. cand J Clin Lab Invest, 1997,57(4):307-315.
12. Oyabu, et al. Nonbacterial transformation of bilirubin in bile. Dig Dis Sci, 1987,32:809-816.
13. Ho, KJ, Hsu SC. Chen JS, Ho LH. Human biliary beta-glucuronidase correlation of its activity with deconjugation of bilirubin in the bile. Eur J Clin Invest, 1986, 6(5):361-367.
14. Ho YC, Ho KJ. Measure of human beta-glucuronidas of its activity in gallbladder bile devoid of intrinsic interference. Dig Dis Sci, 1988,33(4)435-442.
15．黄志强，杨可贞，孟宪钧，等。胆汁β-葡萄糖醛酸酶活性的意义。中华外科杂志，1982，20(1)：49-52．
16．王宏林，郭仁宣，刘小芳，等。乙肝病毒感染者胆汁及血清内源性β-葡萄糖醛酸酶含量与胆红素结石的关系。中华肝胆外科杂志，2001，7(6)：346．
17. Masion A. Hepatitis B virus: replication in diverse cell types during chronic hepatitis B virus infection. Hepatology, 1993,18:781-789.
18. Heathcote EJ, Cauch-Dudek K, Walker V, et al. The Canadian multicenter double blind randomized controlled trial of ursodeoxycholic acid in primary biliary cirrosis. Hepatology, 1999,24:1149,
19. HO KJ. Development and opimization of an enyme-linked immunosorbent assay employing two murine monoclonal antibodies for absolute quantitation of human beta-glucuronidas.Biotech Applied Biochem, 1992,16:1-10.
20．赵青川，樊代明，李开宗，等。ELISA法观察组织源性β-G在原发性肝内胆管结石中的变化。中华肝胆外科杂志。1998，4(5)：25
21．李宁，肖路加，陈世玮，等。胆红素钙结石兔模型β-葡萄糖醛酸酶的变化。华西医科大学学报，1990，21(2)：185-187．
22．杨波，朱善德，杜晓炬，等。肝组织内源性β-葡萄糖醛酸酶与胆红素结石关系的免疫电镜研究．中华外科杂志2000，6(2)：123-125
23. Chen CY, Shiesh SC,Tsao HC, et al. Human biliary beta-glucuronidase activity before and after relief of bile duct obstruction: is it the major role in the formation of pigment gallstones? J Gastroenterol Hepatol. 2000, 15(9): 1071-1075.
24. Stewart L, Oesterle AL, Erdan I, et al. Pathogenesis of pigment gallstones in Western societies the central role of bacteria. J Gastrointest Surg, 2002, 6(6):891-903.
25. Chen CY, Shiesh SC, Lin XZ. Biliary sludge and pigment stone formation in bile duct-ligated guinea pigs. Dig Dis Sci, 1999,44(1):203-209.
26．陈锡谋，黄淑玉，叶惠华，等。非胆道疾病患者胆汁中β-葡萄糖醛酸酶活力测定及临床意义。中华消化杂志，1991，11：363．