胆汁酸在梗阻性黄疸小鼠肝部分切除术后肝再生中作用的研究

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。     

Short-term effects of external and internal biliary drainage on liver and cellular immunity in experimental obstructive jaundice

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.     

Reversibility of leukocyte dysfunction in rats with obstructive jaundice

BACKGROUND: The role of leukocytes in obstructive jaundice is obscure and the effect of relieving cholestasis on leukocyte function is unclear. We postulated that cholestasis affects systemic polymorphonuclear leukocyte function by deranging phagocytosis and hydrogen peroxide release and the leukocyte dysfunction is reversible by internal and external biliary drainage. MATERIALS AND METHODS: Sixty male Sprague Dawley rats were randomly assigned to four groups: obstructive jaundice (OJ), sham operation (SH), OJ with internal drainage (ID), and OJ with external drainage (ED). The phagocytic functions of neutrophils and monocytes in whole blood were measured with flow cytometry using fluorescent microspheres. Intracellular hydrogen peroxide production by leukocytes was assessed with flow cytometry using dihydrorhodamine-123 as probes. RESULTS: Leukocyte count and percentage of monocytes in rats with OJ was significantly increased compared with SH rats (P < 0.001). These elevations could be reversed by both ID and ED method (P < 0.001). The phagocytic function of neutrophils and monocytes was significantly depressed in OJ rats compared with that in SH rats (P < 0.001). After relief of the OJ, the suppressed phagocytic function of neutrophils and monocytes was completely improved in ID rats (ID versus OJ, P < 0.001), but only partially reversed in ED rats. The hydrogen peroxide production by monocytes and lymphocytes was significantly increased in OJ rats (P < 0.05). ID reversed the increased hydrogen peroxide generation (P < 0.05), but ED only partially did. CONCLUSIONS: In our rodent model of biliary obstruction, deranged phagocytosis, and hydrogen peroxide generation by leukocytes was found. Internal drainage is superior to external drainage for reversal of the distorted leukocyte function.     

肝细胞癌侵入胆管致阻塞性黄疸（附16例报告）

目的：探讨肝细胞癌侵入胆管致阻塞性黄疸的诊断与治疗。方法：对1989年1月－1998年12月收治的16例病人的诊断与治疗情况行回顾性分析，结果：术前确诊2例，误诊14例，行肝叶切除，胆管内肿瘤摘除，T管引流2例，胆管内肿瘤摘除，胆管支架及T管引流11例，肿物活检及T管引流2例，1例未及手术死亡，15例病人随访1－14个月，14例于术后6个月内死亡，1例随访14个月仍存活。结论：对黄疸伴有HBsAg阳性，AFOP阳性，肝内有占位，肝内外胆管扩张且其内有占位病变的病人，可诊断为本病，B超，CT，PTC，ERCP为诊断的主要手段。切除肝内原发性肿瘤，疏通胆道为手术治疗的最佳选择。     

Nonoperative internal drainage of obstructive common bile ducts.

A new nonoperative method for internal drainage of common bile duct obstructions by endoscopic retrograde cannulation of the papilla of Vater is described. After introduction of a tube in the common bile duct, a substantial decrease in serum activity of bilirubin, alkaline phosphatase, and gamma-glutamyl transferase was found. In addition, a rapid improvement of the clinical condition could be observed. No serious complications occurred. It is concluded that internal drainage of common bile duct obstructions might be of great value in the preoperative treatment of patients with common bile duct obstructions.     

阻塞性黄疸时肠粘膜免疫功能变化的实验研究

阻塞性黄疸(阻黄)病人机体免疫功能受到抑制。本实验目的是研究阻黄时肠粘膜免疫功能的改变。实验包括阻黄组和对照组,采用胆总管结扎制造阻黄模型,以胆汁外引流组作为对照,每组15只动物。制造阻黄模型后2周,取小肠检测肠液中分泌型IgA(S-IgA)浓度、肠粘膜内淋巴细胞体外刺激转化能力、粘膜固有层内淋巴细胞亚群。结果显示:与对照组相比,阻黄鼠肠液S-IgA浓度降低;肠粘膜内淋巴细胞刺激转化能力降低;粘膜固有层内含IgA浆细胞、CD4阳性和CD8阳性淋巴细胞数目减少,差别有显著性(P>0.05)。因此,我们认为阻黄时肠粘膜免疫功能受到明显抑制。     

胆道梗阻大鼠肝切除术后胆汁内引流和外引流对肝功能及肝再生的影响

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。     

硅胶管搭桥内引流治疗恶性肿瘤致阻塞性黄疸106例分析

目的 探讨晚期胆道、胰腺恶性肿瘤旁路内引流的治疗效果。方法 对106例不能手术切除根治的胆胰恶性肿瘤所引起的阻塞性黄疸病人,采用硅胶管搭桥旁路内引流术。结果 本组无手术死亡,术后黄疸完全消退达到92％,67例得到随访(63.2％)。术后平均生存期为12.3个月,与同期一组41例切除根治术比较(15.7个月),经统计学处理,无显著差异。结论 搭桥旁路内引流术治疗胆胰恶性肿瘤所致阻塞性黄疸,操作简单、创伤小、术后恢复快,不存在术后长期胆汁外流和终生带管等弊端,引流效果确实、可靠,不失为冶疗晚期胆胰恶性肿瘤可取方法。     

Internal biliary drainage improves decreased number of gut mucosal T lymphocytes and MAdCAM-1 expression in jaundiced rats

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.     

Management of Biliary and Duodenal Complications of Chronic Pancreatitis

Biliary stricture and duodenal obstruction have been increasingly recognized as complications of chronic pancreatitis. The anatomical relationship of the distal common bile duct and the duodenum with the head of the pancreas is the main factor for their involvement in chronic pancreatitis. In hospitalized patients with pancreatitis, the incidence of biliary stricture and duodenal obstruction is reported to be about 6% and 1.2%, respectively. For patients requiring an operation for chronic pancreatitis the incidence increases to 35% for biliary stricture and 12% for duodenal obstruction. Fibrosis around the distal common bile duct can cause stenosis with obstruction of bile flow. Clinically, the presentation of these patients ranges from being asymptomatic with elevated alkaline phosphatase or bilirubin, or both, to being septic with cholangitis. Jaundice, cholangitis, hyperbilirubinemia, and persistent elevation of serum alkaline phosphatase occur more frequently in patients with pancreatitis with a biliary stricture. A twofold elevation of alkaline phosphatase is a marker of possible common duct stenosis in patients with chronic pancreatitis. The incidence of both biliary cirrhosis and cholangitis in these patients is about 10%. ERCP reveals a characteristic long, smoothly tapered stricture of the intrapancreatic common bile duct. In duodenal obstruction, the factors that convert self-limiting edema to chronic fibrosis and stricture formation are unknown, but ischemia superimposed on inflammation may be the major cause. These patients present with a prolonged history of nausea and vomiting. Barium studies typically show a long constricting lesion of the duodenum, and endoscopy reveals reactive inflammatory changes in a narrowed duodenum. Operation is indicated in patients with common bile duct strictures secondary to chronic pancreatitis when there is evidence of cholangitis, biliary cirrhosis, common duct stones, progression of stricture, elevation of alkaline phophatase and/or bilirubin for over a month, and an inability to rule out cancer. The operation of choice is either choledochoduodenostomy or choledochojejunostomy. A cholecystoenterostomy is less favored because of its higher failure rate (23%). Endoscopic stenting plays a role in patients who are unfit for surgery, but it is not recommended as definitive therapy. For duodenal obstruction, failure to resolve the obstruction with 1–2 weeks of conservative therapy is an indication for bypass. The operation of choice is a gastrojejunostomy. Not uncommonly, combined obstruction of the pancreatic duct, common bile duct, and duodenum will develop. Combined drainage procedures or resection are used to manage these problems.     

Rapid increase in plasma levels of atrial natriuretic peptide after common bile duct ligation in the rabbit.

Previous studies have shown that common bile duct ligation in the rabbit is followed by a reduction of the extracellular water compartment. To further elucidate the mechanisms leading to volume depletion in this model, water and sodium balances and changes in plasma concentrations of atrial natriuretic peptide (ANP), vasopressin (ADH), plasma renin activity (PRA) and aldosterone (Ald) were investigated during the first 4 days after common bile duct ligation (group OJ,) or sham operation (group SO). Water and chow intakes were lower in group OJ (148 +/- 30 versus 226 +/- 40 mL/4 days; p = 0.004 and 12 +/- 9 versus 171 +/- 40 g/4 days; p = 0.0001). There were no differences in urine output. Sodium urinary losses were marginally higher in group OJ (12.4 +/- 7 versus 6.7 +/- 5 mEq/4 days; p = 0.06). Water balance was lower in group OJ (-50 +/- 56 versus 101 +/- 71 mL/4 days; p = 0.0001). At 24 hours, plasma ANP (41 +/- 7 versus 10.7 +/- 1 fmol/mL, p = 0.0001), ADH (21.8 +/- 7 versus 12.3 +/- 6 pg/mL, p = 0.008) and Ald (14.5 +/- 5 versus 3.7 +/- 3 ng/dL, p = 0.001) were higher in group OJ. These alterations persisted 72 hours after bile duct ligation, when a concomitant increase in PRA (10.7 +/- 5 versus 3 +/- 1.6 ng/dL, p = 0.006) was also observed. A group of pair-fed pair-watered sham-operated controls (group SO2, n = 13) showed a metabolic profile similar to group OJ but a low ANP concentration. Multiple venous sampling in five rabbits 24 hours after bile duct ligation showed the highest plasma levels of ANP in the aorta and infrarenal vena cava. These results suggest that common bile duct ligation in the rabbit is followed by marked hypodipsia and hypophagia, possibly mediated by ANP, leading to isotonic volume depletion and secondary activation of the water and sodium retaining hormones.     

腹腔镜胆总管探查术587例临床分析

目的总结腹腔镜胆总管探查术的治疗经验。方法对1992年6月至2006年5月在我院行腹腔镜胆总管探查术的587例患者的资料进行回顾性分析。结果585例患者行腹腔镜胆总管探查术成功,2例中转开腹,成功率99．7％;手术时间60～230min,平均85min。术后发生胆漏13例,十二指肠损伤1例,腹腔残石致引流管口脓肿形成1例,胆管残石35例,T管引流出钛夹3例。所有患者术后第2天进流质食物并下床活动,平均住院4．6d。结论腹腔镜胆总管探查术对于治疗胆管结石是安全有效的手术方式。     

腹腔镜胆囊切除术后胆道并发症的预防及治疗(附9例报告)

目的:探讨腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)胆道并发症的预防及治疗。方法:回顾分析1995年6月至2010年4月施行6 000例LC术后7例及外院转诊2例胆道损伤的原因及处理措施。结果:9例患者中2例胆漏,经保守治疗痊愈(B超下穿刺引流,内镜鼻胆管引流);1例肝总管横断伤因术后发现较晚、水肿严重,暂行高位胆管引流术;2例术中发现肝总管横断,中转开腹行肝总管空肠Roux-en-Y吻合术,痊愈出院,随访2年,无胆管狭窄;3例术后胆漏,开腹手术,2例胆囊管残端漏行胆囊管结扎术,1例右副肝管胆漏行右副肝管缝合"T"管引流术;1例胆囊管钛夹将胆总管成角钳夹,开腹取夹治愈。全组无死亡病例。结论:解剖变异、病变程度、技术因素是LC导致胆道损伤的常见原因。胆道损伤应及时发现,准确诊断,根据分型正确处理,才能获得满意的预后。     

Measurement of body water compartments after ligation of the common bile duct in the rabbit

To elucidate the pathogenesis of renal insufficiency associated with obstructive jaundice we have studied spontaneous water intake and body water compartments in rabbits undergoing common bile duct ligation. Total body water, extracellular water and plasma volume were measured by multi-isotope dilution technique. During the initial 6 postoperative days spontaneous water intake was 898 ml in sham operated animals (SO) but only 280 ml in jaundiced rabbits (OJ6) (P less than 0.01). Creatinine clearance was almost unchanged in SO but fell to 60 per cent of the preoperative values both in OJ6 and in paired-drink sham operated animals (SO2). There was a 15 per cent decrease in total body water (P less than 0.01) and a 24 per cent decrease in extracellular water (P less than 0.01) 6 days after bile duct ligation. There was a further reduction of the extracellular water to 35 per cent and a 15 per cent reduction of plasma volume 12 days after ligation. Water restriction mimicked the alterations in body composition produced by bile duct ligation. We conclude that bile duct ligation is associated with hypodypsia and a depletion of extracellular water and plasma volume. These alterations could explain the tendency to develop hypotension and renal failure which are associated with obstructive jaundice.     

肝癌合并胆管癌栓的外科手术治疗疗效分析

目的分析肝癌合并胆管癌栓外科手术治疗效果。方法回顾性分析2006年1月~2014年9月于我院接受手术治疗的100例肝癌合并胆管癌栓患者的临床资料。结果①所有患者均根据肝癌类型选择合适的手术方式,其中接受根治性手术58例,包括肿瘤局部切除术+胆总管切开取栓+T管引流术18例,肝叶切除+胆总管切开取栓术+T管引流术40例;接受姑息性手术42例,其中胆总管切开取栓+T管引流术+患侧肝动脉结扎术28例,胆总管切开取栓+T管引流术14例;手术整体切除率为70.00%。②不同外科手术方式治疗肝癌合并胆管癌栓术后并发症发生率相近;③根治性手术患者术后1年、术后2年总生存率为65.52%、44.83%,均高于姑息性手术的19.05%、7.14%,对比差异有统计学意义(P0.05)。结论对无手术禁忌症的肝癌合并胆管癌栓患者建议尽可能行根治性手术治疗,以提高患者术后生存率。     

经皮胆总管探查内置管内引流术治疗胆道多发结石

目的 探讨经皮胆总管探查、内置管内引流手术治疗胆道多发结石的临床效果.方法 回顾性分析2002年3月至2010年9月解放军第四五一医院收治的962例胆总管结石患者的临床资料.全组患者均行LC,采用自制器械行胆总管探查,将内置管放置在胆总管和十二指肠内以内引流胆汁,通过十二指肠注水的膨抽试验确认内置管放入十二指肠,术后30 d经十二指肠镜拔出内置管.结果 全组患者中成功完成经皮胆总管探查、内置管内引流手术864例,中转开腹42例,中转腹腔镜胆总管T管外引流56例.864例患者手术时间为20～72 min,平均手术时间为(36±18)min;术后住院时间为(6.6±2.1)d;术后出现腹膜后腔脓肿经局部引流治疗痊愈2例,出现胆汁漏经保守治疗痊愈32例;术后30 d 862例患者通过B超检查随访,其中603例发现胆总管内置管影像,经十二指肠镜拔出内置管,1例内置管回缩胆总管经EST取出,258例内置管自然脱落.864例患者术后随访1～3年无胆管狭窄,26例胆总管复发结石经EST取出.结论 经皮胆总管探查、内置管内引流手术是治疗胆道多发结石的一种安全而简便的微创方法.

Abstract：

Objective To investigate the efficacy of laparoscopic percutaneous common bile duct exploration (LPCBDE) with internal draining tube placement for the treatment of cholelithiasis. Methods The clinical data of 962 patients with choledocholithiasis who were admitted to the No. 451 Hospital of PLA were retrospectively analyzed. A self-made internal draining tube was placed in the common bile duct and duodenum to drain bile internally. The correct position of the internal draining tube was comfirmed by injecting water into and draining water from duodenum. The internal draining tube was pulled out with the help of duodenoscope at 30 days after the operation. Results LPCBDE with internal draining tube placement was successfully performed on 864 patients. Forty-two patients were transferred to open surgery, and 56 patients were transferred to receive LPCBDE with T-tube drainage. The mean operation time was (36 ± 18) minutes (range, 20-72 minutes), and the length of postoperative hospital stay was (6.6 ±2.1)days. Two patients were complicated with retroperitoneal abscess and they were cured by puncture and drainage, 32 patients were complicated with bile leakage and they were cured by conservative treatment. A total of 862 patients were followed up by B ultrasound at 30 days after the operation. The internal draining tube which was confirmed in the common bile duct was extracted with duodenoscope in 603 patients; the internal draining tube which was drawn back in 1 patient was removed with endoscopic sphincterotomy ( EST); the internal draining tube was removed naturally in 258 patients. The follow-up period ranged from 1 to 3 years, 26 patients had recurrent cholelithiasis and they were treated by EST. Conclusions LPCBDE with internal draining tube placement is a safe and minimally invasive method for the treatment of cholelithiasis.     

三镜同期手术扩大一期缝合术应用范围238例报告

目的 总结运用腹腔镜、胆道镜、十二指肠镜（三镜）同期手术治疗胆囊结石、胆总管结石和乳头狭窄,及扩大一期缝合术应用范围的经验.方法 腹腔镜下行 LC、胆总管切开、胆道镜取石、液电碎石,经腹胆道镜钳道插入输尿管导管或斑马导丝至十二指肠腔,经口十二指肠镜行乳头切开术,一期缝合胆总管切口.结果 扩大一期缝合术应用范围 238 例,术中成功切除胆囊和取净胆总管结石238 例（ 100.0% ）.236 例（ 99.2% ）乳头狭窄切开成功,直接施行一期缝合术,2 例（ 0.8% ）乳头狭窄切开失败者改为 T 管引流术.术后发生轻症胰腺炎 4 例（ 1.7% ）;发生胆漏 7 例（ 2.9% ）,经腹腔引流管引流治愈;无肠穿孔、胆管穿孔、大出血、重症胰腺炎等并发症,无死亡.结论 选择适宜的患者,采用三镜同期手术扩大一期缝合术应用范围是可行、有效和安全的.     

局部胆管内压大小及持续时间对犬胆管壁的影响

目的探讨局部胆管内压大小及持续时间对犬胆管壁的影响。方法设计并自制一内置入式胆管扩张器,体外测试扩张气囊内压力与注水容积及囊径的关系。将20只杂交犬随机分为五组,A组为假手术组仅在胆总管内放置胆管扩张器;B、C组分别向扩张气囊内注水0.1ml、0.2ml（球囊压力分别为0.24Kpa、0.58Kpa）扩张胆总管10min后抽空气囊并留置胆管扩张器作胆汁引流;D、E组分别向扩张气囊内注水0.1ml、0.2ml扩张胆总管后,不抽空气囊并留置作胆汁引流。各组分别术后7天再次剖腹。观察各组扩张前后血清总胆红素（TB）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）值及胆管直径（BD）变化、胆管壁及肝组织学改变。结果与A组比较,C组扩张后BD增宽（P〈0.05）。D组扩张后BD显著增宽（P〈0.01）,E组扩张后TB、ALT、AST均增高（P〈0.01）。A、B组胆管壁组织学无明显变化,C组胆管壁粘膜充血水肿,部分粘膜脱落,D组胆管直径增粗及胆管壁增厚,E组胆管壁部分坏死,与网膜或十二指肠粘连。结论局部胆管内压大小及持续时间对犬胆管壁的影响存在双向互变关系,正常胆管壁在一定的时间内可承受一定的局部胆管内压而不致发生胆管壁的病理变化,适宜的局部胆管内压可引起局部胆管及其上游胆管壁扩张,反之,胆管壁可出现破坏性改变。     

不同胆汁引流方式对梗阻性黄疸大鼠肠黏膜屏障功能的影响及机制

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。     

Development and reversal of endotoxemia and endotoxin-related death in obstructive jaundice

Gut-derived endotoxemia has been implicated in postoperative complications in patients with jaundice. It is thought that absence of bile in the gut predisposes to portal absorption of endotoxin and endotoxemia is reversed by oral bile salt replacement or internal biliary drainage and return of bile to the gut, but not by external drainage. We believe that the importance of gastrointestinal bile flow has been overestimated and biliary obstruction and the integrity of hepatocyte and Kupffer cell function are more important in the development and reversal of endotoxemia. In experiment 1, serum endotoxin concentrations were measured in control rats (n = 10) after choledochovesical fistula (n = 15) and bile duct ligation (n = 15) and after relief of biliary obstruction by internal drainage (choledochoduodenostomy; n = 8) and sterile external drainage (choledochovesical fistula; n = 8), with a quantitative limulus assay. In experiment 2, mortality rates were measured in similar groups 48 hours after administration of oral endotoxin (5 mg/100 gm) and intravenous lead acetate (5 mg/100 gm). Bilirubin levels were elevated in bile duct ligation (192 +/- 13 mumols/L) compared with control animals and those with choledochovesical fistula, internal drainage, and external drainage (10.6 +/- 1.5 mumols/L). In experiment 1, significant portal endotoxemia and systemic endotoxemia occurred in bile duct ligation (portal, 130.4 +/- 12.9 pg/ml; systemic, 91.8 +/- 11.0 pg/ml) but not in choledochovesical fistula (portal, 49.3 +/- 17.1 pg/ml; systemic, 27.2 +/- 11.5 pg/ml). Relief of obstruction by both internal and external drainage reversed endotoxemia. In experiment 2, significant death occurred in bile duct ligation (13 of 15) but not in choledochovesical fistula (3 of 15), and relief of obstruction by both internal and external drainage prevented death. These results confirm that biliary obstruction is a more important factor than is gastrointestinal bile flow in the development and reversal of endotoxemia.