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1.
BACKGROUND: A simple and reproducible rat model that allows studies of the reversal of obstructive jaundice (OJ) by internal (ID) and external (ED) drainage is not available at present. METHODS: OJ was induced in rats by double ligation and division of the common bile duct. To minimize tissue handling and dissection the duodenum was extracted with a ophthalmic muscle hook and the common bile duct isolated using very fine forceps. One week after bile duct ligation, ID was accomplished by implanting a length of infant feeding tube between the dilated bile duct and the duodenum. ED was achieved by placing a PVC tube into the dilated bile duct and exteriorizing the other end at the nape of the neck. RESULTS: Minimal adhesions were found around the dilated common bile duct, which made relaparotomy for drainage easy. Alanine transaminase, total bilirubin, alkaline phosphatase, and gamma-glutamyltransferase were significantly raised after bile duct ligation. All parameters returned to control levels after ID for 7 days. In the ED group plasma albumin was significantly decreased and alkaline phosphatase remained marginally elevated. CONCLUSIONS: We have developed a simple and reproducible rat model that allows for the study of reversal of OJ by ID or ED. We also demonstrated that ID is superior to ED in reversing impaired liver function in OJ.  相似文献   

2.
目的:探讨胆汁酸(CA)在梗阻性黄疸(OJ)小鼠肝部分切除术后肝再生中的作用及机制。 方法:180只健康雄性小鼠随机均分为6组,分别行假手术(对照组)、胆总管结扎(OJ组)、胆总管结扎并于7 d加行外引流(ED组)、胆总管结扎+0.2%CA灌胃并7 d后加行外引流(ED+0.2%CA组)、胆总管结扎+1%CA灌胃并于7 d后加行外引流(ED+1%CA组)、胆总管结扎并于7 d后加行内引流(ID组),各组分别于实验第14天行70%肝切除,且各外引流组改行内引流。检测各组肝切除术后不同时间点肝再生率与肝组织增殖细胞核抗原Ki-67表达、叉状头盒M1b基因(Foxm1b)mRNA相对表达、成纤维细胞生长因子受体4(FGFR4)蛋白表达,并观察部分组肝细胞原位凋亡情况。 结果:除对照组外,肝再生率、肝组织Ki-67阳性表达率、Foxm1b mRNA及FGFR4蛋白表达在其余各组均由高到低依次为:ID组>ED+0.2%CA组>ED组>OJ组>ED+1%CA组,组间差异均有统计学意义(均P<0.05);ID组与对照组间各指标差异均无统计学意义(均P>0.05);肝细胞凋亡率由高到低依次为:ED+1%C组>ED组>ED+0.2%CA组>对照组,组间差异均有统计学意义(均P<0.05)。 结论:内引流通过减少内源性CA的丢失有利于肝切除后肝再生;外源性低浓度CA可以恢复外引流引起的肝再生障碍,可能与其上调Foxm1b与FGFR4的表达从而促进肝再生有关。  相似文献   

3.
Background/Purpose The effects of preoperative biliary drainage for obstructive jaundiced patients are controversial. Although experimental studies have proven the benefit of internal biliary drainage (ID) over external biliary drainage (ED), ID has several clinical problems, such as clogging or tube replacement. The aim of this study was to determine whether there were any differences in T-cell function, liver function, and histology, between rats in ID and ED groups in short-term experiments.Methods Following bile duct ligation (BDL) for 14 days, rats in the ED and ID groups had 7 days of ED and 7 days of ID, respectively. Normal rats were used as negative controls (control group). For positive controls, we used a group with BDL and no drainage (BDL group). Serum bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were measured, splenic T-cell proliferation was assayed to check cellular immunity, and liver histology was examined.Results Recovery of bilirubin and ALT was similar in the ED and ID groups. Recovery of AST was worse in the ID group than in the ED group, but the difference was not statistically significant. Levels of ALP in the BDL and ID groups were significantly higher than those in the control and ED groups. Rats in the BDL group showed a significant decrease in T-cell function compared to the control group. The ED group showed better recovery of T-cell function than the ID group in the 7 days after relief of obstructive jaundice. The livers in the ID group demonstrated histologically moderate interface hepatitis with periportal inflammation and lymphocyte infiltration, which strongly suggested incomplete tube obstruction, but those in the ED group showed minimal change.Conclusions ED is superior to ID concerning the recovery of cellular immunity and liver inflammation in the short-term after relief from biliary obstruction in this model. As the patency of the tube is well maintained in ED compared to ID, patency of the tube is essential to obtain good recovery of cellular immunity, irrespective of the drainage method.  相似文献   

4.
目的:探讨不同胆汁引流方式对梗阻性黄疸(OJ)大鼠肠黏膜功能的影响及其机制。 方法:将60只SD大鼠采用胆总管结扎法制作OJ模型,1周后随机均分为无引流组(不行胆汁引流术),内引流组(行胆汁内引流术)和外引流组(行胆汁外引流术),引流时间1周。以20只假手术大鼠为对照组,实验共2周,结束时分别用ELISA法和Western blot法检测各组血清内毒素水平和小肠黏膜组织闭锁蛋白(occludin)及闭锁小带蛋白1(ZO-1)的表达,并观察小肠黏膜组织形态学改变。 结果:大鼠造模后出现明显的OJ表现,二次手术后,内引流组大鼠一般情况明显好于无引流组和外引流组。无引流组和外引流组OJ大鼠血清内毒素水平明显升高,与对照组比较,差异均有统计学意义(均P<0.01),而无引流组与外引流组间内毒素水平差异无统计学意义(P>0.05);内引流组OJ大鼠血清内毒素水平较无引流组和外引流组明显下降(均P<0.01),与对照组水平无统计学差异(P>0.05)。与对照组比较,无引流组和外引流组OJ大鼠小肠黏膜组织occludin及ZO-1蛋白表达均明显降低(均P<0.01),且外引流组两者表达水平降低较无引流组更为明显(均P<0.01);内引流组OJ大鼠的occludin及ZO-1的表达水平明显高于无引流组和外引流组(均P<0.01),且基本接近对照组(均P>0.05)。病理学观察显示,无引流组和外引流组OJ大鼠肠黏膜结构破坏,大量或中量炎性细胞浸润,而内引流组OJ大鼠组肠黏膜结构完整,仅见少量炎性细胞浸润。 结论:胆汁内引流对OJ大鼠肠黏膜屏障具有保护作用,其机制可能与胆汁维持肠黏膜上皮细胞间紧密连接相关蛋白的表达有关。  相似文献   

5.

目的:探讨不同胆汁引流方式对梗阻性黄疸(OJ)大鼠肠黏膜的影响及机制。 方法:将80只SD大鼠随机均分为假手术组、OJ模型组(模型组)、OJ模型+胆汁内引流组(内引流组);OJ模型+胆汁外引流组(外引流组)。实验共2周,结束时,处死各组大鼠,观察胃黏膜形态学变化,检测血清内毒素、内皮素1(ET-1),胃黏膜ET-1、内皮素受体A(ET-A)mRNA表达。 结果:除假手术组外,各组大鼠均有不同程度的胃黏膜损伤,但内引流组的损伤情况明显较模型组与外引流组为轻;与假手术组比较,模型组和外引流组大鼠血清内毒素、ET-1和胃黏膜ET-1水平和ET-A mRNA表达明显升高,差异均有统计学意义(均P<0.05),内引流组以上指标轻度升高,差异无统计学意义(均P>0.05)。 结论:胆汁内引流对OJ大鼠胃黏膜有保护作用,机制可能与其降低ET-1水平和ET-A的表达有关。

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6.
Children with cholestasis are susceptible to infective complications. This may be attributable to impaired host defense. We postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMN) function by impeding chemotaxis, phagocytosis, and superoxide release, which are all critical in eliciting an adequate immune response. Sprague Dawley rats (225 g) were assigned to three groups: bile duct ligated (BDL), sham (SH), and normal control (NC). On day 21 after operation, PMN and sera were isolated. Chemotactic response to C5a and FMLP (formyl-methionyl-leucyl-phenylalanine), superoxide release, and phagocytic uptake of 14C-labeled Staphylococcus aureus were performed on pooled PMN samples. Results were expressed as mean +/- SD. Serum bilirubin at day 21 was 6.3 +/- 2.9 v 0.1 +/- 0.1 and 0.1 +/- 0 mg/dL (P less than .01) in BDL, SH, and NC groups, respectively. Kinetic studies of PMN phagocytosis demonstrated impaired 14C S aureus uptake by BDL neutrophils at 60 (P less than .05), 90 (P less than .05), and 120 minutes (P less than .05) compared with SH and NC groups. No differences in PMN chemotactic response to C5a and FMLP was observed in BDL, SH and NC groups (43 +/- 14 v 40 +/- 12 and 33 +/- 1, and 43 +/- 20 v 43 +/- 14 and 28 +/- 1 cell per field, respectively). Zymosan stimulated superoxide release did not differ between groups (14.3 +/- 3.6 (BDL) v 15.1 +/- 8.7 (SH) and 12 +/- 2.0 (NC) nmol/30 min/mg cell protein, respectively. Thus, cholestasis impairs neutrophil phagocytosis in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

7.
This study evaluates the effect of experimental biliary obstruction by bile duct ligation (BDL) and biliary drainage on cell-mediated immunity in Wistar rats. Immune status has been assessed by a mitogen stimulation test of T lymphocytes with phytohaemagglutinin. Animals were followed for up to 35 days after BDL. Regression analysis showed a significant negative correlation between lymphocyte function and the period of jaundice (correlation coefficient -0.57, P less than 0.001). Following BDL for 21 days, groups of animals had internal biliary drainage for 7, 14 and 28 days, and external drainage for 14 days. Compared with obstructed animals, 14 days internal drainage was required to improve lymphocyte function (P less than 0.05). Animals which had 14 days of external drainage had significantly lower lymphocyte stimulation than internal drainage animals (P less than 0.05). The results demonstrate that obstructive jaundice produces a progressive reduction of T lymphocyte function. This can be reversed by biliary drainage, internal drainage being more effective than external drainage.  相似文献   

8.
目的:比较胆汁内引流和外引流对胆道梗阻大鼠肝切除术后肝功能及肝再生的影响。方法:将SD大鼠随机分为胆汁内引流组(ID组)、胆汁外引流组(ED组)、对照组,ID组和ED组均行胆总管结扎,对照组行假手术,各组均于术后72 h行部分(70%)肝切除,ID组和ED组同时分别行胆汁内引流与胆汁外引流。分别在肝切除术后0、1、2、3、7 d收集大鼠血清与残余肝组织,检测肝功能指标、肝组织有丝分裂细胞数以及增殖细胞核抗原(PCNA)的表达,并计算各组肝切除术后7 d残肝质量/体质量比值。结果:与对照组比较,ID组和ED组肝切除术后各时间点,血清总胆红素(TBIL)与谷草转氨酶(AST)均明显升高,而白蛋白(ALB)水平明显降低(均P0.05);ID组与ED组间比较,除TBIL水平无统计学差异外(均P0.05),其他两项指标ID组均优于ED组(均P0.05)。与对照组比较,ID组和ED组核分裂细胞数在肝切除术后大多数时间点均明显降低(均P0.05),但ID组核分裂细胞数多于ED组,在肝切除术后2、3 d差异有统计学意义(均P0.05)。肝切除术后,ID组和ED组肝组织PCNA表达量升高的速度与幅度均低于对照组(均P0.05),ID组升高的程度与衰退的速度大于ED组(均P0.05)。与对照组比较,ID组和ED组在肝切除术后7 d的残肝质量/体质量比值均降低(均P0.05),ID组的残肝质量/体重比值明显高于ED组(P0.05)。结论:胆道梗阻的大鼠部分肝切除术后,胆汁内引流可以改善术后肝功能,促进残余肝脏再生。  相似文献   

9.
PURPOSE: Most volatile anesthetics are known to inhibit the oxidative and phagocytic function of neutrophils. In the present study, we investigated the effect of xenon on phagocytosis and respiratory burst activity of neutrophils and monocytes in human whole blood. METHODS: Heparinized whole blood from 22 healthy volunteers was incubated for 60 min in the presence of 65% xenon. Sixty-five percent nitrous oxide was used as a positive control to prove the reliability of our in vitro system. Phagocytosis of fluorescein isothiocyanate labelled, opsonized Escherichia coli (E. coli) by neutrophils and monocytes was measured using flow cytometry. After induction with either N-formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-12-myristate-13-acetate or opsonized E. coli, respiratory burst activity was assessed by measuring the oxidation of dihydrorhodamine 123 to rhodamine 123 with a flow cytometer. RESULTS: Exposure of human whole blood to xenon increased the percentage of neutrophils showing phagocytosis (94 +/- 3% vs 92 +/- 4%; P < 0.01), and the amount of ingested bacteria (P < 0.01). Respiratory burst activity in neutrophils and monocytes was not affected by xenon. Nitrous oxide significantly reduced the percentage of neutrophils showing respiratory burst after FMLP stimulation. Furthermore, E. coli-induced stimulation resulted in a decreased number of reacting neutrophils (84 +/- 15% vs 95 +/- 5%; P < 0.05) and monocytes (70 +/- 22% vs 83 +/- 11%; P < 0.05) as well as a reduced production of hydrogen peroxide in both cell lines compared to control. CONCLUSION: In contrast to nitrous oxide, xenon preserves neutrophil and monocyte antibacterial capacity in vitro.  相似文献   

10.
Sano T  Ajiki T  Takeyama Y  Kuroda Y 《Surgery》2004,136(3):693-699
BACKGROUND: Although the effect of preoperative biliary drainage in patients with obstructive jaundice is controversial, bacterial or endotoxin translocation is one of the main postoperative problem in jaundiced patients. Failure in gut barrier functions causes bacterial translocation; homing and distribution of T lymphocytes in the intestinal lamina propria are important for gut mucosal immune defense. This study was performed to examine whether bile regulates the numbers of T lymphocyte subsets or the expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in experimental jaundice in rats with and without external and internal biliary drainage. METHODS: Four groups of Wistar rats were used: those that received a sham operation (SHAM), common bile duct ligation (CBDL), CBDL followed by external drainage (ED), and CBDL followed by internal drainage (ID). Numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1-positive cells in the lamina propria were counted immunohistochemically in the specimens of jejunum and ileum of each group. Bacterial translocation was examined by culturing from the mesenteric lymph node complex isolated from rats in each group. RESULTS: A significant decrease in numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1-positive cells in the lamina propria was seen in obstructive jaundice, although numbers of peripheral blood lymphocytes increased in comparison with the sham-operated control. The numbers of CD4(+) and CD8(+) T lymphocytes and MAdCAM-1 expression in the lamina propria did not recover to a normal level after external drainage, but did so after internal drainage. Frequencies of bacterial translocation were high in the CBDL and ED group. In contrast, bacterial translocation was not present in any animals in the SHAM group and was at a low percentage in the ID group. CONCLUSIONS: Changes in the number of T lymphocytes and MAdCAM-1 expression are associated with the presence of bile in the gastrointestinal tract and are inversely correlated with the frequency of bacterial translocation induced by CBD ligation. MAdCAM-1 expression maintained by the presence of bile may regulate T-lymphocyte homing to the lamina propria in obstructive jaundice.  相似文献   

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