急性胆道梗阻解除前后肝功能指标变化的实验及临床研究
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摘要
目的：胆道梗阻可导致全身多系统脏器受损，而肝脏是最先受累，其损害也最为严重。胆道梗阻后，反映肝脏功能的许多血清指标出现异常，梗阻解除后也随之恢复。近年来大量动物实验及临床研究对胆道梗阻解除前后肝功能指标的变化进行了研究，但急性胆道梗阻数小时内肝功能指标变化及通过内镜下十二指肠乳头括约肌切开术(EST)及网篮机械碎石术(EML)治疗后肝功能指标恢复情况报道少见。本实验通过动物实验及临床研究测定急性胆道梗阻及梗阻解除后肝功能指标的变化，来探讨急性胆道梗阻早期对肝脏的影响，并观察EST和EML对治疗胆道梗阻的效果和梗阻解除后肝功能恢复情况。
方法：1动物实验选用体重180-220克Wistar大鼠120只，雌雄各半，随机分为四组，每组30只。Ⅰ组(假手术组)，Ⅱ组(胆道梗阻0.5小时)，Ⅲ组(胆道梗阻1小时)，Ⅳ组(胆道梗阻2小时)。术前1％戊巴比妥钠麻醉成功后，无菌条件下，先行气管切开插管，再行剖腹手术，“0”号丝线双重结扎胆总管，制成胆道梗阻动物模型；Ⅰ组不结扎胆总管，Ⅱ组、Ⅲ组、Ⅳ组结扎胆总管。实验结束时下腔静脉取血3ml，行血清丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、总胆汁酸(TBA)，总胆红素(TBIL)、直接胆红素(DBIL)
中文摘要
及 5－胆红素（8EIL）检测。
2临床研究 25例急性胆道梗阻患者，男性 13例，女
性 12例，平均年龄 59岁，病程 lJ天，10例有胆囊切
除术史，并排除其影响肝功能的疾病。人院后根据病情行
十二指肠乳头括约肌切开术（EST入 网篮机械碎石术
旧ML）及内镜下鼻胆管引流（ENBD人 测定其术前及
术后 l、3、7天肝功能指标（ALT、TBA、TBIL、DBIL、
ALP、GGT）。
结果：l 动物实验（）胆道梗阻动物与对照组门
手术组）相比较，血清TBIL、DBIL及6EIL水平均明
显升高，P刃．of，并且各胆道梗阻组之间相比较，差异显
著，P＜O．05；＊81＊厅8L（＊厅）值亦明显升高，P＜0．05，
但各胆道梗阻组差异不显著，Ptoo刀5。＊）11组、Ill组、
IV组血清 ALT、GGT及 TBA水平较对照组明显升高，
P刃刀1，各组之间差异显著，＊功刀5。（）H组、m组
血清＊＊P水平较对照组略升高，但P＞0刀卜W组血清AL P
水平明显升高，P功．01。
2临床研究 门应5例患者中，17例行 EST及 E皿，
8例行EST、E皿及ENBD，术后腹痛缓解，黄疫逐渐消
退，体温降至正常。Q）胆遭梗阻患者术前ALT、hA、
TBIL、DBIL、ALP、GGT均显著高于正常值，术后上述
各值较术前均有不同程度下降，P功刀5。术后第1天，＊LT
较术前下降了39％，TBA下降了36％，TBIL下降了44％，
DBIL下降了 45％，ALP下降了门％，GGT下降 22％；
术后第3天较术前ALT下降60％，hA下降扣％，TBIL
下降 61％，DBIL下降 69％，ALP下降 33％，GGT下
2
中文摘要
降 40％；术后 7天较术前 ALT下降 79％，TBA下降刀％，
TBIL下降79％，DBIL下降90％，ALP下降47％，GGT
下降 56％。TBfr平均每日下降约为 11％，DBIL每日下降
门％，TBA每日下降10％，ALP每日下降7％，GGT每日
下降8％，相比较而言，ALP与GGT下降较为缓慢。
结论1本组动物实验表明急性胆道梗阻数小时内，
即可出现肝功能指标的变化，提示肝赃损害发生。
2临床观察表明内镜下胆道梗阻解除后肝脏功能能较
快得到恢复。内镜下十二指肠乳头括约肌切开术呸ST人
网篮机械碎石术压ML）及吴胆管引流压NBD）是有效
的胆道引流方法。一旦发生胆道梗阻应及时采耿治疗解除
梗阻，减轻对肝脏的损伤。
Objective: Biliary obstruction can lead to damages of multisystem organs and liver was the first influenced and the severest impaired. It was found that a lot of liver function markers were abnormal after biliary obstruction and recovered after relief of biliary obstruction. Recently a lot of experimental and clinical studies were performed on the changes of liver function markers before and after relief of biliary obstruction. But it was little known about the changes of liver function markers shortly after acute biliary obstruction, so was the changes of liver function markers after relief of biliary obstruction by endoscopics treatment. The aim of this study was to discuss the influence of acute biliary obstruction on liver by determining the changes of liver function markers before and after relief of acute biliary obstruction and observed the effect of EST and EML on relief of acute biliary obstruction.
Methods: 1 Experimental study Sixty male Wistar rats and sixty female Wistar rats weighing 180~220g were used in this study. Rats were randomly placed into four experimental groups: group I (N=30 , sham-operated ),
group II (N =30, half an hour after biliary obstruction ), groupIII(N =30, 1 hour after biliary obstruction ), group IV (N =30, 2 hours after biliary obstruction). After an overnight fast, bronchotomy were performed first and a catheter was placed into bronchus under 1% pentobarbital (30mg -kg) intraperitoneal injection anaesthesia. Through an upper midline laparotomy incision, common bile duct was double-ligated (CBDL). Group I only underwent a sham operation that consisted of bronchotomy and laparotomy without CBDL. Group II group III and group IVunderwent CBDL. At the end of the experiment , rats were sacrificed and blood samples were taken from the inferior vena cava. Liver function markers (serum bilirubin , total bile acid, alanine transaminase, alkaline phosphatase , Y -glutamyl transpeptidase )were determined.
2 Clinical study Twenty-five patients , 13 men and 12 women with acute biliary obstruction, were studied .The mean age was 52.5 years and the course of disease was from 1 day to 7days. Ten patitens had cholecystectomy previously. All patients underwent endoscopic sphincterotomy(EST) , mechanical lithotripsy (EML )and eight patients also underwent endoscopic nosabiliary catheter drainage (ENBD). Serum bilirubin, alanine transaminase (ALT) total bile acid (TBA), alkaline phosphatase (ALP) and y -glutamyl transpeptidase (GGT) were measured just before and 1st, 3rd and 7th days after releasing from biliary obstruction.
Results: 1 Experimental study (1) When compared with group I (sham-operated), the levels of serum bilirubku ALT and TBA increased significantly(P less than 0.01) among group IK III and IV and the differences among group II > group III and group IV were found to be significant (P less than 0.05). The ratio of DBIL/TBIL among group II -, group III and group IV also increased when compared with group I (P less than 0.05),but there was no difference among group IK group III and groupIV. (2) The levels of ALP in group II and group III increased slightly ,but there was no statistical significance when compared with group I . And only the level of ALP in group IV increased greatly when compared with group I (P less than 0.01).
2 Clinical study (1) hi all patients , seventeen patients underwent EST and EML and eight patients underwent EST , EML and ENBD. The pain of all patients were relieved after endoscopic treatments. (2) The levels of liver function markers after relief of biliary obstruction decreased significantly (p<0.05) . On the first day after endoscopic treatments, the level of ALT decreased by 39%, TBA decreased by 36%, TBIL decreased by 44%, DBIL decreased by 45%, ALP decreased by 17% and GOT decreased 22%.ON the third day ,ALT decreased by 60%, TBA decreased by 50%, TBIL decreased by 61%, DBIL decreased by 69%, ALP decreased by 33%, GOT
decreased by 40%. On the seventh day, ALT decreased by 79%, TBA decreased b
方法：1动物实验选用体重180-220克Wistar大鼠120只，雌雄各半，随机分为四组，每组30只。Ⅰ组(假手术组)，Ⅱ组(胆道梗阻0.5小时)，Ⅲ组(胆道梗阻1小时)，Ⅳ组(胆道梗阻2小时)。术前1％戊巴比妥钠麻醉成功后，无菌条件下，先行气管切开插管，再行剖腹手术，“0”号丝线双重结扎胆总管，制成胆道梗阻动物模型；Ⅰ组不结扎胆总管，Ⅱ组、Ⅲ组、Ⅳ组结扎胆总管。实验结束时下腔静脉取血3ml，行血清丙氨酸氨基转移酶(ALT)、γ-谷氨酰转肽酶(GGT)、碱性磷酸酶(ALP)、总胆汁酸(TBA)，总胆红素(TBIL)、直接胆红素(DBIL)
中文摘要
及 5－胆红素（8EIL）检测。
2临床研究 25例急性胆道梗阻患者，男性 13例，女
性 12例，平均年龄 59岁，病程 lJ天，10例有胆囊切
除术史，并排除其影响肝功能的疾病。人院后根据病情行
十二指肠乳头括约肌切开术（EST入 网篮机械碎石术
旧ML）及内镜下鼻胆管引流（ENBD人 测定其术前及
术后 l、3、7天肝功能指标（ALT、TBA、TBIL、DBIL、
ALP、GGT）。
结果：l 动物实验（）胆道梗阻动物与对照组门
手术组）相比较，血清TBIL、DBIL及6EIL水平均明
显升高，P刃．of，并且各胆道梗阻组之间相比较，差异显
著，P＜O．05；＊81＊厅8L（＊厅）值亦明显升高，P＜0．05，
但各胆道梗阻组差异不显著，Ptoo刀5。＊）11组、Ill组、
IV组血清 ALT、GGT及 TBA水平较对照组明显升高，
P刃刀1，各组之间差异显著，＊功刀5。（）H组、m组
血清＊＊P水平较对照组略升高，但P＞0刀卜W组血清AL P
水平明显升高，P功．01。
2临床研究 门应5例患者中，17例行 EST及 E皿，
8例行EST、E皿及ENBD，术后腹痛缓解，黄疫逐渐消
退，体温降至正常。Q）胆遭梗阻患者术前ALT、hA、
TBIL、DBIL、ALP、GGT均显著高于正常值，术后上述
各值较术前均有不同程度下降，P功刀5。术后第1天，＊LT
较术前下降了39％，TBA下降了36％，TBIL下降了44％，
DBIL下降了 45％，ALP下降了门％，GGT下降 22％；
术后第3天较术前ALT下降60％，hA下降扣％，TBIL
下降 61％，DBIL下降 69％，ALP下降 33％，GGT下
2
中文摘要
降 40％；术后 7天较术前 ALT下降 79％，TBA下降刀％，
TBIL下降79％，DBIL下降90％，ALP下降47％，GGT
下降 56％。TBfr平均每日下降约为 11％，DBIL每日下降
门％，TBA每日下降10％，ALP每日下降7％，GGT每日
下降8％，相比较而言，ALP与GGT下降较为缓慢。
结论1本组动物实验表明急性胆道梗阻数小时内，
即可出现肝功能指标的变化，提示肝赃损害发生。
2临床观察表明内镜下胆道梗阻解除后肝脏功能能较
快得到恢复。内镜下十二指肠乳头括约肌切开术呸ST人
网篮机械碎石术压ML）及吴胆管引流压NBD）是有效
的胆道引流方法。一旦发生胆道梗阻应及时采耿治疗解除
梗阻，减轻对肝脏的损伤。
Objective: Biliary obstruction can lead to damages of multisystem organs and liver was the first influenced and the severest impaired. It was found that a lot of liver function markers were abnormal after biliary obstruction and recovered after relief of biliary obstruction. Recently a lot of experimental and clinical studies were performed on the changes of liver function markers before and after relief of biliary obstruction. But it was little known about the changes of liver function markers shortly after acute biliary obstruction, so was the changes of liver function markers after relief of biliary obstruction by endoscopics treatment. The aim of this study was to discuss the influence of acute biliary obstruction on liver by determining the changes of liver function markers before and after relief of acute biliary obstruction and observed the effect of EST and EML on relief of acute biliary obstruction.
Methods: 1 Experimental study Sixty male Wistar rats and sixty female Wistar rats weighing 180~220g were used in this study. Rats were randomly placed into four experimental groups: group I (N=30 , sham-operated ),
group II (N =30, half an hour after biliary obstruction ), groupIII(N =30, 1 hour after biliary obstruction ), group IV (N =30, 2 hours after biliary obstruction). After an overnight fast, bronchotomy were performed first and a catheter was placed into bronchus under 1% pentobarbital (30mg -kg) intraperitoneal injection anaesthesia. Through an upper midline laparotomy incision, common bile duct was double-ligated (CBDL). Group I only underwent a sham operation that consisted of bronchotomy and laparotomy without CBDL. Group II group III and group IVunderwent CBDL. At the end of the experiment , rats were sacrificed and blood samples were taken from the inferior vena cava. Liver function markers (serum bilirubin , total bile acid, alanine transaminase, alkaline phosphatase , Y -glutamyl transpeptidase )were determined.
2 Clinical study Twenty-five patients , 13 men and 12 women with acute biliary obstruction, were studied .The mean age was 52.5 years and the course of disease was from 1 day to 7days. Ten patitens had cholecystectomy previously. All patients underwent endoscopic sphincterotomy(EST) , mechanical lithotripsy (EML )and eight patients also underwent endoscopic nosabiliary catheter drainage (ENBD). Serum bilirubin, alanine transaminase (ALT) total bile acid (TBA), alkaline phosphatase (ALP) and y -glutamyl transpeptidase (GGT) were measured just before and 1st, 3rd and 7th days after releasing from biliary obstruction.
Results: 1 Experimental study (1) When compared with group I (sham-operated), the levels of serum bilirubku ALT and TBA increased significantly(P less than 0.01) among group IK III and IV and the differences among group II > group III and group IV were found to be significant (P less than 0.05). The ratio of DBIL/TBIL among group II -, group III and group IV also increased when compared with group I (P less than 0.05),but there was no difference among group IK group III and groupIV. (2) The levels of ALP in group II and group III increased slightly ,but there was no statistical significance when compared with group I . And only the level of ALP in group IV increased greatly when compared with group I (P less than 0.01).
2 Clinical study (1) hi all patients , seventeen patients underwent EST and EML and eight patients underwent EST , EML and ENBD. The pain of all patients were relieved after endoscopic treatments. (2) The levels of liver function markers after relief of biliary obstruction decreased significantly (p<0.05) . On the first day after endoscopic treatments, the level of ALT decreased by 39%, TBA decreased by 36%, TBIL decreased by 44%, DBIL decreased by 45%, ALP decreased by 17% and GOT decreased 22%.ON the third day ,ALT decreased by 60%, TBA decreased by 50%, TBIL decreased by 61%, DBIL decreased by 69%, ALP decreased by 33%, GOT
decreased by 40%. On the seventh day, ALT decreased by 79%, TBA decreased b
引文
1 王跃，石民生，杨翔，等。实验性胆道梗阻对多脏器损害的病理形态学研究。临床与实验病理学杂志，1996，12(3)：270
2 王宇明。内毒素所致肝损害机理的研究进展。国外医学·流行病学·传染病学册，1994，14：175
3 王宇明，丁健，顾长海，等。内毒素／肿瘤坏死因子所致肝细胞损害机制的体外研究。中华传染杂志，1996，14(1)：1～5
4 Bemelmens MH, Gouma DJ, Greve JW, et al. Cytokines tumor necrosis factor and interleukin-6 m experimental biliary obstruction in mice. Hepatology, 1992, 15: (10)1132～1136
5 王志伟，刘宪棠，黄宇琦，等。梗阻性黄疸患者血清肿瘤坏死因子生物学活性变化及其意义。广东医学，1998，19(7)：487～488
6 张蒙，苏映军，陈璧，等。内毒素及肿瘤坏死因子对肝细胞超微结构的影响。第四军医大学学报，1999，20(5)：389～391
7 Muriel P, Suarez OR.The role of lipid peroxidation in liver damage .Poli G ,Albano E ,Dianzam MU. Chem Phys Lipids, 1987,15(2-4): 117～142
8 Muriel P, Suarez OR.Role of lipid peroxidation in biliary obstruction in the rat.. J Appl toxicol, 1994, 14(6): 423～426
9 李靖，迟延邦，方学军。犬胆道梗阻后肝脏超氧化物歧化酶及过氧化脂质的损伤。中华普外基础与临床杂志，1998，5(3)：148～149
10 洪明理，黄向红，李云生，等。实验胆汁性肝硬化形成机制的病理研究。首都医科大学学报，1996，17(1)：36～39
11 Blandert N, Agrenil G. Presence of bilirubian linded covalently to albumin in serum of patients with cholestasis. Gastroenterology, 1982,34(8);1222～1224
12 吴问汉，杨尹默，黄莛庭。梗阻性黄疸胆红素代谢的实验研究。中华外科杂志，2001，7(5)：288～291
13 Kountouras J, Scherer PJ, Billing BH. Effect of prolonged bile duct obstruction in the rat on the hepatic transport of bilirubin. Clin Sci, 1985, 68(3)341～347
14 黄恩芳，张文，高玲，等。干化学法与湿化学法检测血清胆红素的比较。陕西医学检验，2001，16(2)：12～14
15 Yamaguchi T, Terakado M, Horio-F, et al .Role of bilirubin as an antioxidant in ischemia-reperfusion of rat liver and inductiong of heme oxygenase .Biochem Biophys Res Commun, 1996,223(1)129～135
16 Ossola JO, Tomato ML. Heme oxygenase induction by UVA radiation. A response to oxidative stess in rat liver. Int J Biochem Cell Biol, 1998,30:285～292
17 徐学峥主编。生理化学与医学．第2版，北京：北京科学技术出版社，1987：346
18 林举义，周志华。血清总胆汁酸测定对肝胆疾病的临床意义。重庆医学，2000，29(4)：314～315
19 魏有仁，孙先高，蔡湄。血清总胆汁酸的酶法测定及其评价。中华医学检验杂志，1993，16(1)：11～13
20 Walkan RW. Alkaline phosphatase and cholestasis. Ann Clin Biochem, 1986,23(5):405～412
21 Toda G, Ikeda Y, Kako M et al. Mechanism of elevation of serum alkaline phosphatase activity in biliary obstruction: an experimental study .Clin Chim Acta, 1980, 107(1):85～76
22 Seeharam S et al. The mechanism of elevated alkaline phosphatase activity after bile duct ligation in the rat. Hepatology, 1986, 6(3):374-380
23 梁扩寰主编。肝脏病学1995年1版，北京：人民卫生出版社，1995：212。
24 张学文，何而斯泰，王春艳，等。肝病理形态学计量与其功能关系的研究。临床肝胆病杂志，1998，14(1)：93～95
25 顾生旺，戴琳，侯金林，骆抗先。血清谷丙转氨酶水平与肝脏病理改变程度相关性探讨。江苏医学杂志，2000，20(12)：955～956
2 王宇明。内毒素所致肝损害机理的研究进展。国外医学·流行病学·传染病学册，1994，14：175
3 王宇明，丁健，顾长海，等。内毒素／肿瘤坏死因子所致肝细胞损害机制的体外研究。中华传染杂志，1996，14(1)：1～5
4 Bemelmens MH, Gouma DJ, Greve JW, et al. Cytokines tumor necrosis factor and interleukin-6 m experimental biliary obstruction in mice. Hepatology, 1992, 15: (10)1132～1136
5 王志伟，刘宪棠，黄宇琦，等。梗阻性黄疸患者血清肿瘤坏死因子生物学活性变化及其意义。广东医学，1998，19(7)：487～488
6 张蒙，苏映军，陈璧，等。内毒素及肿瘤坏死因子对肝细胞超微结构的影响。第四军医大学学报，1999，20(5)：389～391
7 Muriel P, Suarez OR.The role of lipid peroxidation in liver damage .Poli G ,Albano E ,Dianzam MU. Chem Phys Lipids, 1987,15(2-4): 117～142
8 Muriel P, Suarez OR.Role of lipid peroxidation in biliary obstruction in the rat.. J Appl toxicol, 1994, 14(6): 423～426
9 李靖，迟延邦，方学军。犬胆道梗阻后肝脏超氧化物歧化酶及过氧化脂质的损伤。中华普外基础与临床杂志，1998，5(3)：148～149
10 洪明理，黄向红，李云生，等。实验胆汁性肝硬化形成机制的病理研究。首都医科大学学报，1996，17(1)：36～39
11 Blandert N, Agrenil G. Presence of bilirubian linded covalently to albumin in serum of patients with cholestasis. Gastroenterology, 1982,34(8);1222～1224
12 吴问汉，杨尹默，黄莛庭。梗阻性黄疸胆红素代谢的实验研究。中华外科杂志，2001，7(5)：288～291
13 Kountouras J, Scherer PJ, Billing BH. Effect of prolonged bile duct obstruction in the rat on the hepatic transport of bilirubin. Clin Sci, 1985, 68(3)341～347
14 黄恩芳，张文，高玲，等。干化学法与湿化学法检测血清胆红素的比较。陕西医学检验，2001，16(2)：12～14
15 Yamaguchi T, Terakado M, Horio-F, et al .Role of bilirubin as an antioxidant in ischemia-reperfusion of rat liver and inductiong of heme oxygenase .Biochem Biophys Res Commun, 1996,223(1)129～135
16 Ossola JO, Tomato ML. Heme oxygenase induction by UVA radiation. A response to oxidative stess in rat liver. Int J Biochem Cell Biol, 1998,30:285～292
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