胆汁内外引流术对解除梗阻性黄疸作用的实验研究
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摘要
【背景与目的】梗阻性黄疸患者术后并发症及死亡率较高。目前对于术前是否解除梗阻、解除梗阻的时机以及内外引流术哪种方式更好尚存在争议。我们之前研究发现,梗阻性黄疸大鼠肝脏枯否细胞产生大量具有细胞毒性的一氧化氮,胆汁内引流术可以逆转这种改变,而外引流却不能,但机理不清楚。本研究通过比较胆汁内外引流术对梗阻性黄疸大鼠血浆内毒素水平、血清细胞因子浓度及肝脏诱导型一氧化氮合酶(iNOS)表达水平的不同影响,进一步探讨胆汁内引流术解除术前黄疸优于外引流术的机制。
【材料与方法】采用成年SD雄性大鼠69只,随机分为四组,分别建立梗阻性黄疸(OJ,n=18)、胆汁内引流术(ID,n=18)、胆汁外引流术(ED,n=18)及假手术(SH,n=15)模型。第一次手术建立梗阻性黄疸模型;饲养7天后,第二次手术建立胆汁内、外引流模型。于第二次术后第7d留取血液标本及肝脏组织标本。通过鲎试验动态浊度法测定大鼠血浆内毒素(LPS)水平,采用双抗体夹心酶联免疫吸附法(ELISA)检测血清白介素-2(IL-2)、及白介素-6(IL-6)水平,并通过SABC免疫组化方法测定肝脏组织iNOS的表达情况。
【结果】成功建立了四组大鼠动物模型。梗阻性黄疸时,大鼠血浆内毒素水平(42.463 pg/mL±3.486 pg/mL)明显高于假手术对照组(4.136±2.002pg/mL)(OJ vs ED,P=0);血清IL-6及IL-2浓度升高(212.949 pg/mL±56.546pg/mL,212.718 pg/mL±62.419 pg/mL);肝组织iNOS表达阳性面积增加(30.539±6.255),平均光密度升高(0.296±0.055)。行胆汁外引流术后,大鼠内毒素血症得到改善(6.224±2.996 pg/mL)(ED vs OJ,P=0),血清IL-2及IL-6水平不降反升(264.890±62.322 pg/mL,269.363±76.199 pg/mL)(P=0.017,P=0.014),肝组织iNOS表达阳性面积及平均光密度亦增加(38.186±7.495,0.399±0.086)(P=0,P=0.004)。而通过胆汁内引流术解除黄疸后,大鼠血浆LPS及血清IL-6浓度均明显下降(4.190±1.970pg/mL,169.713±49.053 pg/mL)(ID vs OJ,P=0,P=0.014),几乎恢复至正常水平,与假手术对照组相比无明显差异(P=0.787,P=0.256);血清IL-2水平虽有所下降(184.313±52.408 pg/mL),但与梗阻性黄疸组相比,无统计学意义(P=0.106);肝脏iNOS表达明显受到抑制,阳性表达面积减少(16.571±2.044)(P=0.017),平均光密度下降(0.204±0.029)(P=0)。
【结论】胆汁内引流术可明显改善梗阻性黄疸时内毒素血症及细胞因子分泌紊乱,抑制肝脏iNOS表达;而胆汁外引流术作用不明显,甚至使大鼠免疫功能恶化,进一步证实胆汁内引流术解除黄疸优于外引流术。
[Backgrounds and Objective] Obstructive jaundice is associated with high postoperative complications and mortality. It is controversial whether or not to relieve the jaundice before operation and which method is better, internal biliary drainage or external biliary drainage. Our previous study has found that a great amount of cytotoxic nitric oxide was produced by Kupffer cells in rats with obstructive jaundice. The elevated nitric oxide could be suppressed by internal biliary drainage, but not by external drainage, although the mechanism remains unclear yet. The aims of the present study are to explore the effects of internal and external biliary drainages on the blood levels of endotoxin (LPS) and cytokines and the expression of inducible nitric oxide synthase (iNOS) by liver tissue in rats with obstructive jaundice, in order to investigate the mechanism of internal biliary drainage being superior to external drainage.
[Methods] Sixty-nine male adult Sprague-Dawley rats were randomly assigned to four groups: obstructive jaundice (OJ, n=18), internal biliary drainage (ID, n=18), external drainage (ED, n=18) and sham operation (SH, n=15). OJ was established by first operation. After seven days, both ID and ED were builded by another operation. On the 7th day after the second operation, the rats were succumbed and the specimens of blood and liver were collected. The level of serum endotoxin was detected by limulus test (LT). The concentrations of serum interlukin-2 (IL-2) and interlukin-6 (IL-6) were measured with enzyme linked immunosorbent assay (ELISA) and the iNOS expression of liver tissue was determined by SABC (Streptavidin Biotin Peroxidase complex technique) immunohistochemical method.
[Results] Rat models were successfully established. After bile duct ligation, the level of plasma endotoxin was significantly elevated (42.463 pg/mL±3.486 pg/mL) compared with that in SH rats (4.136±2.002 pg/mL ) ( OJ vs ED, P=0 ) . The concentrations of serum IL-6 (212.949 pg/mL±56.546 pg/mL) and EL-2 (212.718 pg/mL±62.419 pg/mL) were also increased and the expression of liver iNOS became stronger in terms of staining area and mean optical density ( 30.539±6.255, 0.296±0.055 respectively ) . When ED was performed, rat endotoxemia was depressed (6.224±2.996 pg/ mL) (ED vs OJ, P=0) . However, the level of interlukin-2 and interlukin-6 was far from decrease and was significantly elevated (264.890±62.322 pg/mL, 269.363±76.199 pg/mL) (ED vs OJ, P=0. 017and P=0. 014 respectively). Meanwhile, the expression of liver iNOS i.e. the staining area (38.186±7.495) and mean optical density (0.399±0.086) was obviously stronger (ED vs OJ, P = 0 and P = 0. 004 respectively ). After relief of OJ by ID, the plasma endotoxin and IL-6 were decreased (4.190±1.970 pg/mL, 169.713±49.053 pg/mL) (ID vs OJ, P=0 and P=0. 014 respectively) and comparable to those in SH group (4.136±2.002 pg/mL, 145.308±38.757 pg/mL) (ID vs SH, P=0. 787 and P=0. 256 respectively ) . The concentration of serum EL-2 was decreased a little bit, but it was not statistically significant (ID vs OJ, P=0. 106 ) . The expression of liver iNOS was markedly suppressed. The staining area of iNOS was reduced (16.571±2.044) (ID vs OJ, P=0. 017 )and mean light optical decreased (0.204±0.029) (ID vs OJ, P=0) .
[Conclusions] Internal biliary drainage could reverse the endotoxemia, elevated serum inflammatory cytokines and the expression of iNOS of liver tissue in rats with obstructive jaundice. However, external biliary drainage failed to do that and even deteriorated it. This study further proved that internal biliary drainage is superior to external drainage in the relief of obstructive jaundice.
【材料与方法】采用成年SD雄性大鼠69只,随机分为四组,分别建立梗阻性黄疸(OJ,n=18)、胆汁内引流术(ID,n=18)、胆汁外引流术(ED,n=18)及假手术(SH,n=15)模型。第一次手术建立梗阻性黄疸模型;饲养7天后,第二次手术建立胆汁内、外引流模型。于第二次术后第7d留取血液标本及肝脏组织标本。通过鲎试验动态浊度法测定大鼠血浆内毒素(LPS)水平,采用双抗体夹心酶联免疫吸附法(ELISA)检测血清白介素-2(IL-2)、及白介素-6(IL-6)水平,并通过SABC免疫组化方法测定肝脏组织iNOS的表达情况。
【结果】成功建立了四组大鼠动物模型。梗阻性黄疸时,大鼠血浆内毒素水平(42.463 pg/mL±3.486 pg/mL)明显高于假手术对照组(4.136±2.002pg/mL)(OJ vs ED,P=0);血清IL-6及IL-2浓度升高(212.949 pg/mL±56.546pg/mL,212.718 pg/mL±62.419 pg/mL);肝组织iNOS表达阳性面积增加(30.539±6.255),平均光密度升高(0.296±0.055)。行胆汁外引流术后,大鼠内毒素血症得到改善(6.224±2.996 pg/mL)(ED vs OJ,P=0),血清IL-2及IL-6水平不降反升(264.890±62.322 pg/mL,269.363±76.199 pg/mL)(P=0.017,P=0.014),肝组织iNOS表达阳性面积及平均光密度亦增加(38.186±7.495,0.399±0.086)(P=0,P=0.004)。而通过胆汁内引流术解除黄疸后,大鼠血浆LPS及血清IL-6浓度均明显下降(4.190±1.970pg/mL,169.713±49.053 pg/mL)(ID vs OJ,P=0,P=0.014),几乎恢复至正常水平,与假手术对照组相比无明显差异(P=0.787,P=0.256);血清IL-2水平虽有所下降(184.313±52.408 pg/mL),但与梗阻性黄疸组相比,无统计学意义(P=0.106);肝脏iNOS表达明显受到抑制,阳性表达面积减少(16.571±2.044)(P=0.017),平均光密度下降(0.204±0.029)(P=0)。
【结论】胆汁内引流术可明显改善梗阻性黄疸时内毒素血症及细胞因子分泌紊乱,抑制肝脏iNOS表达;而胆汁外引流术作用不明显,甚至使大鼠免疫功能恶化,进一步证实胆汁内引流术解除黄疸优于外引流术。
[Backgrounds and Objective] Obstructive jaundice is associated with high postoperative complications and mortality. It is controversial whether or not to relieve the jaundice before operation and which method is better, internal biliary drainage or external biliary drainage. Our previous study has found that a great amount of cytotoxic nitric oxide was produced by Kupffer cells in rats with obstructive jaundice. The elevated nitric oxide could be suppressed by internal biliary drainage, but not by external drainage, although the mechanism remains unclear yet. The aims of the present study are to explore the effects of internal and external biliary drainages on the blood levels of endotoxin (LPS) and cytokines and the expression of inducible nitric oxide synthase (iNOS) by liver tissue in rats with obstructive jaundice, in order to investigate the mechanism of internal biliary drainage being superior to external drainage.
[Methods] Sixty-nine male adult Sprague-Dawley rats were randomly assigned to four groups: obstructive jaundice (OJ, n=18), internal biliary drainage (ID, n=18), external drainage (ED, n=18) and sham operation (SH, n=15). OJ was established by first operation. After seven days, both ID and ED were builded by another operation. On the 7th day after the second operation, the rats were succumbed and the specimens of blood and liver were collected. The level of serum endotoxin was detected by limulus test (LT). The concentrations of serum interlukin-2 (IL-2) and interlukin-6 (IL-6) were measured with enzyme linked immunosorbent assay (ELISA) and the iNOS expression of liver tissue was determined by SABC (Streptavidin Biotin Peroxidase complex technique) immunohistochemical method.
[Results] Rat models were successfully established. After bile duct ligation, the level of plasma endotoxin was significantly elevated (42.463 pg/mL±3.486 pg/mL) compared with that in SH rats (4.136±2.002 pg/mL ) ( OJ vs ED, P=0 ) . The concentrations of serum IL-6 (212.949 pg/mL±56.546 pg/mL) and EL-2 (212.718 pg/mL±62.419 pg/mL) were also increased and the expression of liver iNOS became stronger in terms of staining area and mean optical density ( 30.539±6.255, 0.296±0.055 respectively ) . When ED was performed, rat endotoxemia was depressed (6.224±2.996 pg/ mL) (ED vs OJ, P=0) . However, the level of interlukin-2 and interlukin-6 was far from decrease and was significantly elevated (264.890±62.322 pg/mL, 269.363±76.199 pg/mL) (ED vs OJ, P=0. 017and P=0. 014 respectively). Meanwhile, the expression of liver iNOS i.e. the staining area (38.186±7.495) and mean optical density (0.399±0.086) was obviously stronger (ED vs OJ, P = 0 and P = 0. 004 respectively ). After relief of OJ by ID, the plasma endotoxin and IL-6 were decreased (4.190±1.970 pg/mL, 169.713±49.053 pg/mL) (ID vs OJ, P=0 and P=0. 014 respectively) and comparable to those in SH group (4.136±2.002 pg/mL, 145.308±38.757 pg/mL) (ID vs SH, P=0. 787 and P=0. 256 respectively ) . The concentration of serum EL-2 was decreased a little bit, but it was not statistically significant (ID vs OJ, P=0. 106 ) . The expression of liver iNOS was markedly suppressed. The staining area of iNOS was reduced (16.571±2.044) (ID vs OJ, P=0. 017 )and mean light optical decreased (0.204±0.029) (ID vs OJ, P=0) .
[Conclusions] Internal biliary drainage could reverse the endotoxemia, elevated serum inflammatory cytokines and the expression of iNOS of liver tissue in rats with obstructive jaundice. However, external biliary drainage failed to do that and even deteriorated it. This study further proved that internal biliary drainage is superior to external drainage in the relief of obstructive jaundice.
引文
[1] Isenberg, G., Gouma, D.J., Pisters, P.W.. The on-going debate about perioperative biliary drainage in jaundiced patients undergoing pancreaticoduodenectomy. Gastrointest Endosc. 2002, 56: 310-315.
[2] Mayer R, Stranzl H, Prettenhofer U, et al. Palliative treatment of unresectable bile duct tumours. Acta Med Austriaca. 2003, 30:10-12.
[3] Tomazic A, Pleskovic A. Surgical outcome after pancreatoduodenectomy: effect of preoperative biliary drainage[J]. Hepatogastroenterology. 2006, 53(72): 944-946.
[4] Kamiya S, Nagino M, Kanazawa H, et al. The value of bile replacement during external biliary drainage: an analysis of intestinal permeability, integrity, and microflora. Ann Surg. 2004, 239:510-7.
[5] Mizuta A, Chijiiwa K, Saiki S, et al. Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal, external, or no biliary drainage. Eur Surg Res. 2002, 34: 291-299.
[6] Daglar GO, Kama NA, Atli M, et al. Effect of 5-lipoxygenase inhibition on Kupffer cell clearance capacity in obstructive jaundiced rats. J Surg Res. 2001, 96: 158-162.
[7] Assimakopoulos SF, Thomopoulos KC, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest. 2006, 36(3): 181-7.
[8] Assimakopoulos SF, Vagianos CE, Patsoukis N, et al. Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats. Acta Physiol Scand. 2004, 180:177-85.
[9] Li W, Sung JJ, Chung SC. Reversibility of leukocyte dysfunction in rats with obstructive jaundice. J Surg Res. 2004, 116(2):314-21.
[10] Mok KT, Wang BW, Chang HC, et al. External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice. Dig Dis Sci. 2001, 46:1864-70.
[11] Li W., Tse, J. Y., James, A. E., et al. Delivery and scavenging system for small animal inhalational anesthesia. J. Surg Res. 99: 175,2001.
[12] Li W, Chung, S.C.S. An improved rat model of obstructive jaundice and its reversal by internal and external drainage. J Surg Res. 2001, 101: 4-15.
[13] Sewnath ME, Karsten TM, Prins MH, et al. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann. Surg. 2002, 236: 17-27.
[14] Pisters PW, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann. Surg. 2001, 234: 47-55.
[15] Povoski SP, Karpeh MSJ, Conlon KC, et al. Association of pre-operative biliary drainage with postoperative outcome following pancreaticoduodenectomy. Ann. Surg. 1999, 230: 131-42.
[16] Mok KT, Wang BW, Chang HC, et al. External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice. Dig Dis Sci. 2001, 46:1864-70.
[17] Tomazic A, Pleskovic A. Surgical outcome after pancreatoduodenectomy: effect of preoperative biliary drainage. Hepatogastroenterology. 2006, 53: 944-946.
[18] Duffas JP, Suc B, Msika S, et al. A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy. Am J Surg. 2005,189: 720-729.
[20] Sano T, Ajiki T, Takeyama TY, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats. Surg. 2004, 136:693-699.
[21] Kimmings AN, van Deventer SJ, Obertop H, et al. Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage[J].Gut.2000,46(5):725-731.
[22]Miyaso H,Morimoto Y,Ozaki M,et al.Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation:possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes[J].Gastroenterol Hepatol.2005,20(12):1859-1866.
[23]Reynolds JV,Murchan P,Leonard N,et al.Gut barrier failure in experimental obstructive jaundice[J].J Surg Res.1996,62(1):11-16.
[24]Neil SO,Hunt J,Filk ins J,et al.Obstructive jaundice in rats results in exaggerated hepatic production of tumor necrosis factor-alpha and systemic and tissue tumor necrosis factor-alpha levels after endotoxin.Surgery.1997,122:281
[25]Su GL,Klein RD,Aminlari A,et al.Kupffer cell activation by lipopolysaccharide in rats:role for lipopolysaccharide binding protein and Toll-like receptor 4[J].Hepatology.2000,31(4):932-936.
[26]Dobrovolskaia M,Vogel SN.Toll-like receptors,CD14,and macrophage activation and deactivation by LPS[J].Microbes Infect.2002,4(9):903-914.
[27]Yuceyar H,Kokuludag A,Coker A,et al.The serum levels of soluble interleukin-2 receptor levels in patients with obstructive jaundice[J].Hepatogastroenterology.1996,43(10):949-953.
[28]Sano T,Ajiki T,Takeyama TY,et al.Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1expression in jaundiced rats[J].Surgery,2004,136(3):693-699.
[29]Lentsch AB,Edwards MJ,Sims DE,et al.N omega—nitro—L—arginine methyl ester inhibits inflammatory liver injury induced by interleukin-2[J],J Leukoc Biol.1998,63(1):22-30.
[30]侯森林,乔占英,康建省等.支架与手术引流对梗阻性黄疸患者免疫功能的影响[J].中华消化内镜杂志.2005,22(1):46-47.
[1]郭宇廷,余秀专,周怀文等.一氧化氮在梗阻性黄疸患者肝损伤中的作用及其意义.肝胆外科杂志.2004,12:458-460.
[2]Utkan T,Sarioglu Y,Utkan NZ,et al.Vascular smooth muscle reactivity and endothelium derived relaxing factor in experimental obstructive jaundice.Arch Physiol Biochem.1996,104:30-35.
[3]Li W,Chan ACW,Lau JYW,et al.Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice:Effect of internal and external drainage.Journal of Gastroenterology and Hepatology 2004,19:160-165.
[4]杨文军,雷正是,李代渝,等.一氧化氮、内皮素21在内毒素所致肝脏损伤中的作用机制研究[J].肝胆外科杂志.2002,10(1):68-70.
[5]Meng Y,Yang YS,Li W.Internal biliary drainage is superior to external drainage in reversing the serum tumor necrosis factor-alpha and the expression of inducible nitric oxide synthase mRNA by Kupffer cells in rats with obstructive jaundice.Gastrointestinal Endoscopy.2007;65(supplement).
[6]Rnonld D,Curran MD,Timothy R,et al.Multiple cytokines are required induce hepatocyte nitric oxide production and inhibit total protein synthesis.Ann Surg.1990,10:462-4691.
[7]E.Ohta M,Yamaguchi S,Gotoh N,et al.Pathogenesis of portal hypertensive gastropathy:a clinical and experimental review.Surgery.2002,131(1 pt 2):165-170.
[8]Arriero MM,Lopez-Farre A,Fryeiro O,et al.Expression of inducible nitric oxide synthase in the liver of bile duct-ligated Wistar rats with modulation by lymhomononuclear cells.Surgery.2001,129(3):255-66.
[9]Sano T,Ajiki T,Takeyama TY,et al.Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats. Surgery. 2004, 136:693-699.
[1] Tomioka M, Iinuma H, Okinaga K. Impaired kupffer cell function and effect of immunotherapy in obstructive jaundice. J Surg Res. 2000, 92:276-282.
[2] Assimakopoulos SF, Thomopoulos KC, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest. 2006, 36(3): 181-7.
[3] Assimakopoulos SF, Vagianos CE, Patsoukis N, et al. Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats. Acta Physiol Scand. 2004,180:177-85.
[4] Clements MD, McCaigue M, Erw in P, et al. Billiary decompression promote Kupffer cell recovery in obstructive jaundice.Gut. 1996, 38 (6): 925.
[5] Li W, Sung JJ, Chung SC. Reversibility of leukocyte dysfunction in rats with obstructive jaundice. J Surg Res. 2004,116(2):314-21.
[6] Su GL, Klein RD, Aminlari A, et al. Kupffer cell activation by lipopolysaccharide in rat: role for lipopolysaccharide binding protein and Toll - like receptor 4[J ]. Hepatology. 2000, 31 : 932 - 936.
[7] Dobrovolskaia M, Vogel SN. Toll - like receptors, CD14, and macrophage activation and deactivation by LPS [ J ]. Microbes Infect. 2002,4 : 903 - 914.
[8] Yorganci K, Baykal A, Kologlu M, et al. Endotoxin challenge causes a proinflammatory state in obstructive jaundice. J Invest Surg. 2004,17(3): 119-26.
[9] Hideaki M, Youinori M, Michttaka O, et al. Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes. Gastroenterology Hepatol. 2005, 20 (12) ,1859-1866.
[10] Kennedy JA, Clements WD. Characterization of the Kupffer cell response to exogenous in a rodent model of obstructive jaundice. J Surg. 1999, 86(5): 628-633.
[11] Okamura K, Noshima S, Esato K. Cytokine release during hypoxia reoxygenation by Kupffer cells in rats with obstructive jaundice. Surg Today, 1999,29(8):730-734.
[12]Kang BY,Chung SW,Im SY,et al.Sulfasalazine prevents T-helper 1immune response by suppressing interleukin-12 production in macrophages.Immunology.1999,98:98-103.
[13]Morgan DA,Ruscetti FW,Gallo R.Selectibe vitro growth of lymphocytes from normal human bone marrows.Science.1976,193:1007.
[14]Gaffen SL,Liu KD.Overview of interleukin-2 function,production and clinical applications[J].Cytokine.2004,28(3):109-123.
[15]Pender MP.Activation induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance[J].Immunol Cell Biol.1999,77(3):216-223.
[16]李桦,熊叔陶,罗毅等.阻塞性黄疸患者免疫状态及精氨酸免疫调节的研究.中华实验外科杂志.1994,11:1.
[17]Scott-Conner CE,Hall JJ,Anglin BL,et al.Serum and celluar factors in murine obstructive jaundice.Surgery.1994,115:77.
[18]Raitakari M,Brown RD,Sze D,et al,T-cell expansions in patients with multiple myeloma have a phenotype of cytotoxic T cells[J].Br J Haematol.2000,110(1):203-207.
[19]Kaya Y,Atac B,Murat K,et al.Endotoxin Challenge Causes a Proinflammatory State in Obstructive Jaundice[J].Invest Surg.2004,17:119-126.
[20]宫路路,林瑞新,文海荣等.精氨酸对恶性梗阻性黄疸患者肿瘤坏死因子-α和可溶性白细胞介素2受体的影响.肝胆外科杂志.2007,15(4):297-298.
[21]Murakami S,Satomi A,Ishida K,et al.Serum soluble interleukin-2 receptor concentrations in patients with gastric cancer.Cancer.1994,74:2745-2748.
[22]李炳辉,于忠信.在梗阻性黄疸大白鼠SIL-2的变化.黑龙江医药.2007,20(3),226-228。
[23]薛平,胡以则,卢海武等.恶性梗阻性黄疸内镜胆管引流对免疫功能的 影响.中华普通外科杂志.2000,15(6):377-378.
[24]Fausto N,Campbell JS,Riehle KJ.Liver regeneration.Hepatology.2006,43(2 Suppl 1):S45-53.
[25]Kerek M,Akyurek N,Sozuer EM,et al.Effects of recombinant platelet activateing factor acetylhydrolase in obstructive jaundice.Hepatogastroenterology.2003,50(52):1097-100.
[26]Kimura F,Miyazaki M,Suwa T,et al.Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy.J Gastroenterol Hepatol.2001,16:467-72.
[27]Kimmings AN,van Deventer SJ,Obertop H,et al.Endotoxin,cytokines,and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage.Gut.2000,46:725-31.
[28]Fumio K,Masaru M,Toshikazu S,et al.Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy.Gastroenterology and Hepatology,2001,16,467-472.
[29]Akiyama T,Hasegawa T,Sejima T,et al.Serum and bile interleukin 6 after percutaneous transhepatic cholangio-drainage.Hepatogastroenterology.1998,45:665-671.
[30]Kimura F,Miyazaki M,Suwa T et al.Serum interleukin-6 levels in patients with biliary obstruction.Hepatogastroenterology 1999,46:1613-1617.
[31]Padillo FJ,Andicoberry B,Muntane J.Cytokines and acute-phase response markers derangements in patients with obstructive jaundice.epatogastroenterology.2001,48(38):378-381.
[32]Liu TZ,Lee KT,Chern CL,et al.Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.Ann Clin Lab Sci.2001,31(4):383-90.
[33]李立,冉江华,陆晓青.检测阻塞性黄疸患者手术前后细胞因子的临床意义.中国普外基础与临床杂志.2000,7,3.
[34] Takaoka M, Kubota Y, Tsuji K,et al. Human neutrophil functions in obstructive jaundice. Hepatogastroenterology. 2001,48(37):71-75.
[35] Kimmings AN, Deventer SJ, Rauws EAJ, Huibregste K, Gouma DJ. Systemic inflammatory response in acute cholangitis and after subsequent treatment. Eur J Surg. 2000, 166:700-705.
[36] Bemelmans MH, Greve JW, Gouma DJ, et al. Increased concentrations of tumour necrosis factor (TNF) and soluble TNF receptors in biliary obstruction in mice; Soluble TNF receptors as prognostic factors for mortality. Gut. 1996, 38:447-453.
[37] Padillo FJ, Cruz A, Segura-J, et al. Anti-TNF-alpha treatment and bile duct drainage restore cellular immunity and prevent tissue injury in experimental obstructive jaundice. Int J Immunopathol Pharmacol. 2007,20(4):855-60.
[2] Mayer R, Stranzl H, Prettenhofer U, et al. Palliative treatment of unresectable bile duct tumours. Acta Med Austriaca. 2003, 30:10-12.
[3] Tomazic A, Pleskovic A. Surgical outcome after pancreatoduodenectomy: effect of preoperative biliary drainage[J]. Hepatogastroenterology. 2006, 53(72): 944-946.
[4] Kamiya S, Nagino M, Kanazawa H, et al. The value of bile replacement during external biliary drainage: an analysis of intestinal permeability, integrity, and microflora. Ann Surg. 2004, 239:510-7.
[5] Mizuta A, Chijiiwa K, Saiki S, et al. Differences in biliary lipid excretion after major hepatectomy in obstructive jaundiced rats with preoperative internal, external, or no biliary drainage. Eur Surg Res. 2002, 34: 291-299.
[6] Daglar GO, Kama NA, Atli M, et al. Effect of 5-lipoxygenase inhibition on Kupffer cell clearance capacity in obstructive jaundiced rats. J Surg Res. 2001, 96: 158-162.
[7] Assimakopoulos SF, Thomopoulos KC, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest. 2006, 36(3): 181-7.
[8] Assimakopoulos SF, Vagianos CE, Patsoukis N, et al. Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats. Acta Physiol Scand. 2004, 180:177-85.
[9] Li W, Sung JJ, Chung SC. Reversibility of leukocyte dysfunction in rats with obstructive jaundice. J Surg Res. 2004, 116(2):314-21.
[10] Mok KT, Wang BW, Chang HC, et al. External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice. Dig Dis Sci. 2001, 46:1864-70.
[11] Li W., Tse, J. Y., James, A. E., et al. Delivery and scavenging system for small animal inhalational anesthesia. J. Surg Res. 99: 175,2001.
[12] Li W, Chung, S.C.S. An improved rat model of obstructive jaundice and its reversal by internal and external drainage. J Surg Res. 2001, 101: 4-15.
[13] Sewnath ME, Karsten TM, Prins MH, et al. A meta-analysis on the efficacy of preoperative biliary drainage for tumors causing obstructive jaundice. Ann. Surg. 2002, 236: 17-27.
[14] Pisters PW, Hudec WA, Hess KR, et al. Effect of preoperative biliary decompression on pancreaticoduodenectomy-associated morbidity in 300 consecutive patients. Ann. Surg. 2001, 234: 47-55.
[15] Povoski SP, Karpeh MSJ, Conlon KC, et al. Association of pre-operative biliary drainage with postoperative outcome following pancreaticoduodenectomy. Ann. Surg. 1999, 230: 131-42.
[16] Mok KT, Wang BW, Chang HC, et al. External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice. Dig Dis Sci. 2001, 46:1864-70.
[17] Tomazic A, Pleskovic A. Surgical outcome after pancreatoduodenectomy: effect of preoperative biliary drainage. Hepatogastroenterology. 2006, 53: 944-946.
[18] Duffas JP, Suc B, Msika S, et al. A controlled randomized multicenter trial of pancreatogastrostomy or pancreatojejunostomy after pancreatoduodenectomy. Am J Surg. 2005,189: 720-729.
[20] Sano T, Ajiki T, Takeyama TY, et al. Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats. Surg. 2004, 136:693-699.
[21] Kimmings AN, van Deventer SJ, Obertop H, et al. Endotoxin, cytokines, and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage[J].Gut.2000,46(5):725-731.
[22]Miyaso H,Morimoto Y,Ozaki M,et al.Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation:possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes[J].Gastroenterol Hepatol.2005,20(12):1859-1866.
[23]Reynolds JV,Murchan P,Leonard N,et al.Gut barrier failure in experimental obstructive jaundice[J].J Surg Res.1996,62(1):11-16.
[24]Neil SO,Hunt J,Filk ins J,et al.Obstructive jaundice in rats results in exaggerated hepatic production of tumor necrosis factor-alpha and systemic and tissue tumor necrosis factor-alpha levels after endotoxin.Surgery.1997,122:281
[25]Su GL,Klein RD,Aminlari A,et al.Kupffer cell activation by lipopolysaccharide in rats:role for lipopolysaccharide binding protein and Toll-like receptor 4[J].Hepatology.2000,31(4):932-936.
[26]Dobrovolskaia M,Vogel SN.Toll-like receptors,CD14,and macrophage activation and deactivation by LPS[J].Microbes Infect.2002,4(9):903-914.
[27]Yuceyar H,Kokuludag A,Coker A,et al.The serum levels of soluble interleukin-2 receptor levels in patients with obstructive jaundice[J].Hepatogastroenterology.1996,43(10):949-953.
[28]Sano T,Ajiki T,Takeyama TY,et al.Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1expression in jaundiced rats[J].Surgery,2004,136(3):693-699.
[29]Lentsch AB,Edwards MJ,Sims DE,et al.N omega—nitro—L—arginine methyl ester inhibits inflammatory liver injury induced by interleukin-2[J],J Leukoc Biol.1998,63(1):22-30.
[30]侯森林,乔占英,康建省等.支架与手术引流对梗阻性黄疸患者免疫功能的影响[J].中华消化内镜杂志.2005,22(1):46-47.
[1]郭宇廷,余秀专,周怀文等.一氧化氮在梗阻性黄疸患者肝损伤中的作用及其意义.肝胆外科杂志.2004,12:458-460.
[2]Utkan T,Sarioglu Y,Utkan NZ,et al.Vascular smooth muscle reactivity and endothelium derived relaxing factor in experimental obstructive jaundice.Arch Physiol Biochem.1996,104:30-35.
[3]Li W,Chan ACW,Lau JYW,et al.Superoxide and nitric oxide production by Kupffer cells in rats with obstructive jaundice:Effect of internal and external drainage.Journal of Gastroenterology and Hepatology 2004,19:160-165.
[4]杨文军,雷正是,李代渝,等.一氧化氮、内皮素21在内毒素所致肝脏损伤中的作用机制研究[J].肝胆外科杂志.2002,10(1):68-70.
[5]Meng Y,Yang YS,Li W.Internal biliary drainage is superior to external drainage in reversing the serum tumor necrosis factor-alpha and the expression of inducible nitric oxide synthase mRNA by Kupffer cells in rats with obstructive jaundice.Gastrointestinal Endoscopy.2007;65(supplement).
[6]Rnonld D,Curran MD,Timothy R,et al.Multiple cytokines are required induce hepatocyte nitric oxide production and inhibit total protein synthesis.Ann Surg.1990,10:462-4691.
[7]E.Ohta M,Yamaguchi S,Gotoh N,et al.Pathogenesis of portal hypertensive gastropathy:a clinical and experimental review.Surgery.2002,131(1 pt 2):165-170.
[8]Arriero MM,Lopez-Farre A,Fryeiro O,et al.Expression of inducible nitric oxide synthase in the liver of bile duct-ligated Wistar rats with modulation by lymhomononuclear cells.Surgery.2001,129(3):255-66.
[9]Sano T,Ajiki T,Takeyama TY,et al.Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats. Surgery. 2004, 136:693-699.
[1] Tomioka M, Iinuma H, Okinaga K. Impaired kupffer cell function and effect of immunotherapy in obstructive jaundice. J Surg Res. 2000, 92:276-282.
[2] Assimakopoulos SF, Thomopoulos KC, Patsoukis N, et al. Evidence for intestinal oxidative stress in patients with obstructive jaundice. Eur J Clin Invest. 2006, 36(3): 181-7.
[3] Assimakopoulos SF, Vagianos CE, Patsoukis N, et al. Evidence for intestinal oxidative stress in obstructive jaundice-induced gut barrier dysfunction in rats. Acta Physiol Scand. 2004,180:177-85.
[4] Clements MD, McCaigue M, Erw in P, et al. Billiary decompression promote Kupffer cell recovery in obstructive jaundice.Gut. 1996, 38 (6): 925.
[5] Li W, Sung JJ, Chung SC. Reversibility of leukocyte dysfunction in rats with obstructive jaundice. J Surg Res. 2004,116(2):314-21.
[6] Su GL, Klein RD, Aminlari A, et al. Kupffer cell activation by lipopolysaccharide in rat: role for lipopolysaccharide binding protein and Toll - like receptor 4[J ]. Hepatology. 2000, 31 : 932 - 936.
[7] Dobrovolskaia M, Vogel SN. Toll - like receptors, CD14, and macrophage activation and deactivation by LPS [ J ]. Microbes Infect. 2002,4 : 903 - 914.
[8] Yorganci K, Baykal A, Kologlu M, et al. Endotoxin challenge causes a proinflammatory state in obstructive jaundice. J Invest Surg. 2004,17(3): 119-26.
[9] Hideaki M, Youinori M, Michttaka O, et al. Obstructive jaundice increases sensitivity to lipopolysaccharide via TLR4 upregulation: Possible involvement in gut-derived hepatocyte growth factor-protection of hepatocytes. Gastroenterology Hepatol. 2005, 20 (12) ,1859-1866.
[10] Kennedy JA, Clements WD. Characterization of the Kupffer cell response to exogenous in a rodent model of obstructive jaundice. J Surg. 1999, 86(5): 628-633.
[11] Okamura K, Noshima S, Esato K. Cytokine release during hypoxia reoxygenation by Kupffer cells in rats with obstructive jaundice. Surg Today, 1999,29(8):730-734.
[12]Kang BY,Chung SW,Im SY,et al.Sulfasalazine prevents T-helper 1immune response by suppressing interleukin-12 production in macrophages.Immunology.1999,98:98-103.
[13]Morgan DA,Ruscetti FW,Gallo R.Selectibe vitro growth of lymphocytes from normal human bone marrows.Science.1976,193:1007.
[14]Gaffen SL,Liu KD.Overview of interleukin-2 function,production and clinical applications[J].Cytokine.2004,28(3):109-123.
[15]Pender MP.Activation induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance[J].Immunol Cell Biol.1999,77(3):216-223.
[16]李桦,熊叔陶,罗毅等.阻塞性黄疸患者免疫状态及精氨酸免疫调节的研究.中华实验外科杂志.1994,11:1.
[17]Scott-Conner CE,Hall JJ,Anglin BL,et al.Serum and celluar factors in murine obstructive jaundice.Surgery.1994,115:77.
[18]Raitakari M,Brown RD,Sze D,et al,T-cell expansions in patients with multiple myeloma have a phenotype of cytotoxic T cells[J].Br J Haematol.2000,110(1):203-207.
[19]Kaya Y,Atac B,Murat K,et al.Endotoxin Challenge Causes a Proinflammatory State in Obstructive Jaundice[J].Invest Surg.2004,17:119-126.
[20]宫路路,林瑞新,文海荣等.精氨酸对恶性梗阻性黄疸患者肿瘤坏死因子-α和可溶性白细胞介素2受体的影响.肝胆外科杂志.2007,15(4):297-298.
[21]Murakami S,Satomi A,Ishida K,et al.Serum soluble interleukin-2 receptor concentrations in patients with gastric cancer.Cancer.1994,74:2745-2748.
[22]李炳辉,于忠信.在梗阻性黄疸大白鼠SIL-2的变化.黑龙江医药.2007,20(3),226-228。
[23]薛平,胡以则,卢海武等.恶性梗阻性黄疸内镜胆管引流对免疫功能的 影响.中华普通外科杂志.2000,15(6):377-378.
[24]Fausto N,Campbell JS,Riehle KJ.Liver regeneration.Hepatology.2006,43(2 Suppl 1):S45-53.
[25]Kerek M,Akyurek N,Sozuer EM,et al.Effects of recombinant platelet activateing factor acetylhydrolase in obstructive jaundice.Hepatogastroenterology.2003,50(52):1097-100.
[26]Kimura F,Miyazaki M,Suwa T,et al.Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy.J Gastroenterol Hepatol.2001,16:467-72.
[27]Kimmings AN,van Deventer SJ,Obertop H,et al.Endotoxin,cytokines,and endotoxin binding proteins in obstructive jaundice and after preoperative biliary drainage.Gut.2000,46:725-31.
[28]Fumio K,Masaru M,Toshikazu S,et al.Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy.Gastroenterology and Hepatology,2001,16,467-472.
[29]Akiyama T,Hasegawa T,Sejima T,et al.Serum and bile interleukin 6 after percutaneous transhepatic cholangio-drainage.Hepatogastroenterology.1998,45:665-671.
[30]Kimura F,Miyazaki M,Suwa T et al.Serum interleukin-6 levels in patients with biliary obstruction.Hepatogastroenterology 1999,46:1613-1617.
[31]Padillo FJ,Andicoberry B,Muntane J.Cytokines and acute-phase response markers derangements in patients with obstructive jaundice.epatogastroenterology.2001,48(38):378-381.
[32]Liu TZ,Lee KT,Chern CL,et al.Free radical-triggered hepatic injury of experimental obstructive jaundice of rats involves overproduction of proinflammatory cytokines and enhanced activation of nuclear factor kappaB.Ann Clin Lab Sci.2001,31(4):383-90.
[33]李立,冉江华,陆晓青.检测阻塞性黄疸患者手术前后细胞因子的临床意义.中国普外基础与临床杂志.2000,7,3.
[34] Takaoka M, Kubota Y, Tsuji K,et al. Human neutrophil functions in obstructive jaundice. Hepatogastroenterology. 2001,48(37):71-75.
[35] Kimmings AN, Deventer SJ, Rauws EAJ, Huibregste K, Gouma DJ. Systemic inflammatory response in acute cholangitis and after subsequent treatment. Eur J Surg. 2000, 166:700-705.
[36] Bemelmans MH, Greve JW, Gouma DJ, et al. Increased concentrations of tumour necrosis factor (TNF) and soluble TNF receptors in biliary obstruction in mice; Soluble TNF receptors as prognostic factors for mortality. Gut. 1996, 38:447-453.
[37] Padillo FJ, Cruz A, Segura-J, et al. Anti-TNF-alpha treatment and bile duct drainage restore cellular immunity and prevent tissue injury in experimental obstructive jaundice. Int J Immunopathol Pharmacol. 2007,20(4):855-60.