Altered Serum Transforming Growth Factor-ß1 and Monocyte Chemoattractant Protein-1 Levels in Obstructive Jaundice

Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-ß1 (TGFß1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFß1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFß1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFß1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFß1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFß1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.     

Effect of Oral Glutamine Administration on Bacterial Tanslocation, Endotoxemia, Liver and Ileal Morphology, and Apoptosis in Rats with Obstructive Jaundice

Postoperative complications in patients with obstructive jaundice remain increased when associated with endotoxemia and the inflammatory response due to gut barrier failure. Administration of glutamine has been proposed to maintain the integrity of the gut mucosa and thus reduce bacterial translocation (BT), but the effects of this pretreatment on apoptosis and histologic morphology of various organs affected by BT in obstructive jaundice have not been studied. We therefore studied the effects of oral glutamine supplementation on endotoxemia, BT, liver and terminal ileal morphology, and apoptosis in an experimental model of obstructive jaundice. A total of 60 male Wistar rats were randomly divided into four groups of 15 each: I, controls; II, sham-operated; III, bile duct ligation (BDL); IV, BDL + glutamine (4.5 g/kg/day in drinking water). Ileal samples for histology, DNA and protein content, liver biopsies, mesenteric lymph nodes (MLNs) for culture, and portal and systemic blood samples for endotoxin measurements were obtained 10 days later. Compared to the controls, a significant increase in contaminated MLN and liver samples and increased endotoxemia were noted in group III (p < 0.01) but were significantly reduced in group IV (p < 0.05). Group IV also had a significantly higher number of mitoses per crypt (M/c) (p < 0.05), less apoptotic body counts (ABCs) (p < 0.05), and a higher DNA content than did group III (p < 0.05). Liver biopsies from group III displayed typical changes of large duct obstruction that significantly improved after glutamine treatment, with decreased ductular proliferation. We concluded that supplementation of oral glutamine in the presence of obstructive jaundice ameliorates BT, endotoxemia, and apoptosis and improves the ileal and liver histology.     

Effect of Probiotic Supplementation on Bacterial Translocation in Thermal Injury

Purpose To examine the effects of probiotic supplementation and enteral solutions containing glutamine and arginine on bacterial translocation (BT) and intestinal villous atrophy in thermal injury.Methods Forty male Sprague-Dawley rats weighing 200–250 g were divided into four groups of ten. Group 1 served as control group without thermal injury and was fed standard chow. Thermal injury was inflicted as a 30% scald burn in the other three groups. Group 2 was fed standard chow and group 3 was fed standard chow supplemented with a probiotic (Acidophilus plus) containing Bifidobacterium bifidum, Lactobacillus acidophilus, and Lactobacillus bulgaricus (2 × 10⁹ CFU/day) via an orogastric tube. Group 4 was fed only an enteral diet (Stresson multifiber) containing glutamine, arginine, and medium chain triglyceride, at 1 g/kg per day amino acid and 230 kcal/kg, for 7 days before thermal injury. All the animals were killed 24 h after thermal injury, and ileal segments were resected and examined histopathologically. To evaluate BT, samples from blood, mesenteric lymph nodes, and cecal content were cultured under aerobic and anaerobic conditions. Terminal ileum specimens were histologically examined to evaluate mucosal integrity.Results Significantly less BT was seen in groups 3 and 4 than in group 2 (P < 0.001). No significant difference was found between groups 3 and 4. Histological evaluation showed significant reduction in villous atrophy in groups 3 and 4.Conclusion Probiotic supplementation seems to reduce bacterial translocation and decrease intestinal mucosal atrophy in rats with thermal injury, as do enteral solutions with arginine and glutamine.     

Probiotic supplementation reduces the risk of bacterial translocation in experimental short bowel syndrome

Background/Purpose: Probiotics are live organisms that survive passage through the gastrointestinal tract and have beneficial effects on the host. Lactobacillus and Bifidobacterium have been recommended for cholesterol lowering, acute diarrhea, prevention of cancer, or inflammatory bowel disease. On the other hand, after massive bowel resection, bacterial overgrowth is frequent and favors bacterial translocation (BT). The possible beneficial effects of Bifidobacterium lactis (BL) administration on BT in experimental short bowel syndrome (SBS), have not been investigated. The aim of this study was to test the hypothesis that BL administration decreases BT in SBS in animals fed orally. Methods: One hundred twenty-eight adult Wistar rats fed orally with standard rat chow and tap water [ldquo ]ad libitum[rdquo ] were maintained in individual metabolic cages for 10 days and divided into 3 groups: control group (n = 71): nonmanipulated animals; RES group (n = 39): 80% gut resection from 10 cm beyond the angle of Treitz to 10 cm above the cecum; RES-PRO group (n = 18): same resection and daily 7.8 [times ] 10⁸ CFU B Lactis administration, after orogastric intubation. At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood specimens were recovered and cultured. Bacterial identification in blood was made by conventional methods, and MLN culture was considered positive with a growth over 100 CFU/g. Results: Bacterial translocation was detected in 6% of control group rats. The incidence of BT in the RES group was 87% (34 of 39), whereas only 50% (9 of 18) of RES-PRO animals had BT (P [lt ] .05). The relative risk reduction (RRR) was 0.43 (95% Cl 0.14 to 0.72), and the number needed to treat (NNT) was 3 (95% Cl 2 to 8). In other words, animals that received BL had the risk of BT reduced by 43% (RRR of 0.43), and of every 3 animals treated, 1 is expected to be free of BT (NNT of 3). Conclusion: Administration of B Lactis reduces the incidence of BT in adult Wistar rats after 80% gut resection.     

Gut glutamine metabolism at different stages of sepsis in rats

Abstract. Purpose: To investigate gut glutamine metabolism and determine the effects of glutamine supplementation in different stages of sepsis in a rat model. Methods: Sepsis was induced by cecal ligation and puncture (CLP), and control rats underwent a sham operation. In the first experiment, a continuous infusion of normal saline was started at the end of the operation. Intestinal blood flow, glutamine concentrations of the abdominal aorta and superior mesenteric vein (SMV) were measured, and gut glutamine extraction and flux were calculated 5 h after the sham operation, and 5 and 20 h after CLP, being groups Ia (n= 9), Ib (n= 8), and Ic (n= 8), respectively. In the second experiment, animals received a continuous infusion of alanyl-glutamine instead of normal saline and were divided into groups IIa (n= 8), IIb (n= 8), and IIc (n= 6). The same parameters were measured in each group and compared with those of the corresponding group in the first experiment. Results: In the first experiment, no significant difference in SMV blood flow was seen among the groups. The arterial glutamine concentration was increased in group Ic (P < 0.05) compared with that in groups Ia and Ib. Gut glutamine extraction was significantly increased in group Ib (P < 0.01) and significantly decreased in group Ic (P < 0.05) compared with that in group Ia. In the second experiment, gut glutamine flux was significantly increased in group Ilb (P < 0.01) compared with that in group Ib, but the increase did not reach statistical significance between groups Ia and IIa or between groups Ic and IIc. Conclusion: These results indicate that intestinal glutamine uptake is increased and glutamine utilization is enhanced by glutamine supplementation in early sepsis. Received: August 24, 2001 / Accepted: March 5, 2002     

Glucan and glutamine reduce bacterial translocation in rats subjected to intestinal ischemia-reperfusion.

Intestinal ischemia/reperfusion (I/R) may induce bacterial translocation (BT). Glutamine (GLN)-enriched nutrition decreases BT. However, little is known about the effect of glucan (GL) in BT. This study investigated the combined effect of GL/GLN on BT, intestinal damage, and portal blood cytokines in animals under I/R. Four groups of 10 rats each were subjected to 60 min of intestinal ischemia and 120 min of reperfusion. The control group (group 1) received only rat food/water, group 2 received glutamine via gavage, group 3 received subcutaneuos soluble (1, 3)-d-glucan, and group 4 received GL + GLN. A sham group (group 5) served as a normal control. Bacterial cultures of ileum, mesenteric lymph nodes (MLN), liver and lung biopsies, histological changes of ileum, and serum cytokines variables were examined after I/R. Data were analyzed by analysis of variance (ANOVA) and the Newman-Keuls test. Results showed that GLN, GL, and GL/GLN significantly reduced BT to MLN, liver, and lung. BT was more attenuated after GL treatment than GLN (P < .05). Rats treated with both GL and GLN exhibited lower bacterial colony counts than the ones treated only with GLN or GL. Severe mucosal damage on histological findings was shown in group 1, but these findings were significantly ameliorated (P < .05) in groups 3 and 4. Tumor necrosis factor (TNF)-a and interleukin (IL)-6 levels in portal serum were significantly reduced and IL-10 was increased by GL and GLN treatment. In conclusion, the use of GL was more effective than GLN in reducing BT, intestinal damage, and cytokine levels after I/R. Additionally, the combination of GL and GLN improved results.     

Effects of Antibiotics and <Emphasis Type="Italic">Saccharomyces boulardii</Emphasis> on Bacterial Translocation in Burn Injury

Purpose To investigate the effects of antibiotics and the probiotic, Saccharomyces boulardii, on indigenous microflora and bacterial translocation (BT) in burned rats.Methods Twenty-three male albino rats were divided into a sham burn group (group 1, n = 7) exposed to 21°C water, a burn + antibiotic group (group 2, n = 8), and a burn + antibiotic + S. boulardii group (group 3, n = 8) exposed to 95°C water for 10s, producing a full-thickness burn to 30% of the total body surface area. Ampicillin-sulbactam (1000mg/kg per day) was given as two doses via an orogastric feeding tube to groups 2 and 3. Saccharomyces boulardii (1mg/g body weight per day) was given as two doses via the same route to group 3. All rats were killed on the fifth day postburn and cultures of the mesenteric lymph nodes, liver, spleen, blood, and cecal contents were done.Results The incidences of BT were 0% (0/7) in group 1, 87.5% (7/8) in group 2, and 37.5% (3/8) in group 3. A significant increase in the BT incidence was found in group 2 (P 0.01), while a significant decrease was found in group 3 when compared with group 1. The total bacteria count of cecal flora was significantly lower in group 3 than in group 1 (P 0.01). The decrease in Gram-negative bacteria in the cecal flora was significant in group 3.Conclusion These results suggest that the incidence of BT in burn injury is enhanced by using an antibiotic, and that S. boulardii decreases the incidence of antibiotic-induced BT. Thus, we conclude that S. boulardii can effectively protect the intestinal ecologic equilibrium and prevent BT in burn injury victims.     

Enteral donor pre-treatment with ursodeoxycholic acid protects the liver against ischaemia-reperfusion injury in rats

Liver donor pre-treatment with ursodeoxycholic acid (UDCA) may protect against injury during transplantation. In the present study we evaluated whether enteral administration of UDCA has an effect on bile flow and protects the liver from injury related to transplantation. Wistar rats were used in liver perfusion (LP) and transplantation (LTx) models. Rats were enterally administered UDCA (800 mg/kg) 3 h before cold perfusion. In LP, bile flow and bile acid composition were analysed. In LTx, serum ALT and liver histology were analysed. LP showed biliary UDCA enrichment up to 36±13% in pre-treated rats, causing higher bile flow (P=0.026) compared with control rats. LTx showed lower ALT and TUNEL positive hepatocytes in the UDCA group (P<0.02 and P<0.05). In conclusion, augmented bile salt-dependent bile flow is preserved in the liver after cold storage. Enteral donor pre-treatment with UDCA protects the liver against ischaemia-reperfusion injury.     

Glutamine-induced heat shock protein protects against renal ischaemia-reperfusion injury in rats

Aim: To find out if a single dose of glutamine can relieve acute renal ischaemia‐reperfusion injury in rats, to explore the role of heat shock protein in this process. Methods: Forty‐eight Sprague–Dawley rats were assigned to four groups: saline as control group; glutamine group; quercetin (heat shock protein inhibitor) plus glutamine group; and quercetin plus saline group. The renal ischaemia‐reperfusion rat model was established 1 h after drug administration. Serum creatinine (CR) and blood urea nitrogen (BUN) were analyzed. The kidneys were harvested to evaluate the degree of renal injuries. Heat shock protein expression was detected by immunohistochemistry and western blot. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and apoptosis index was calculated. Results: Statistical data from CR, BUN, haematoxylin–eosin (HE) dyeing and TUNEL assay results showed that ischaemia‐reperfusion injury and cell apoptosis in the glutamine group were significantly milder than those in control group (P < 0.05), while ischaemia‐reperfusion injury and cell apoptosis in the quercetin plus glutamine group and quercetin plus saline group were more severe than those in the control group (P < 0.05). Statistical data from immunohistochemistry and western blot results showed that heat shock protein expression was enhanced in the glutamine group compared with that in the control group (P < 0.01), while it was weaker in the quercetin plus glutamine group and quercetin plus saline group than that in the control group (P < 0.01). Conclusion: Our experiment suggested that a single dose of glutamine could relieve renal ischaemia‐reperfusion injury in rats in 24 h, and its mechanism may be associated with enhanced heat shock protein expression. This finding may provide a new alternative for protecting against clinical renal ischaemia‐reperfusion injury.     

Effect of different enteral nutrients on bacterial translocation in experimental obstructive jaundice

Obstructive jaundice leads to bacterial translocation (BT) by disruption of the gut barrier, intestinal microecology, and impaired host immune defence. The objective of the present study is to investigate the effects of different enteral nutrients on BT that is induced by obstructive jaundice in rats. Eighty male Wistar-Albino rats were randomly assigned into 4 groups. Group 1: 20 rats underwent laparotomy, common bile duct (CBD) was not actually ligated and transected, but sham ligation of CBD was performed. Groups 2-4: 60 rats underwent laparotomy, CBD ligation and transection. Group 1 and 2 rats were given rat chow, group 3 rats were fed a glutamine and arginine supplemented enteral diet, and group 4 rats were fed an arginine, m-RNA and omega-3 supplemented enteral diet, an immunonutrient. Rats in groups 3 and 4 had significantly less BT to mesenteric lymph nodes compared to rats in group 2 (p = 0.001). These findings suggest that oral administration of an arginine and glutamine supplemented diet and immunonutrition reduce BT in rats with obstructive jaundice.     

The role of antibiotic prophylaxis with sodium ceftriaxone to prevent bacterial translocation associated with hypovolemic shock: an experimental study in rats.

One of the measures adopted to reduce or prevent intestinal bacterial translocation (BT) in patients who are in hemorrhagic shock consists of prophylactic antibiotics. This study attempted to assess the effectiveness of administering systemic antibiotic to suppress BT in rats submitted to hemorrhagic shock. Sixty-eight male Wistar rats were divided into two experiments. In experiment 1 (n = 28), the animals were randomly divided into three groups: group I (n = 7), sham operation; group II (n = 11), constituted by animals that were submitted to hemorrhagic shock by removing 40% of the volemia, and were resuscitated after 40 min of sustained shock, replacing the previously removed blood; and group III (n = 10), animals that, besides hemorrhagic shock and volemic replacement, received 50 mg/kg of sodium ceftriaxone intravenous 1 min after blood readministration. Mesenteric lymph nodes (MLN) for culture tests and segments of the small bowel were removed for histopathological studies 1 day after the operation in the three groups. In experiment 2, the same procedures were performed, except the laparotomy for removing MLN and segments of jejunal and ileal bowel, but the animals were followed during 7 days, in order to evaluate the mortality rate. In the control group (group I), the bacteriological assessment of the MLN was negative in all cases. Only 40% of the animals treated with antibiotics after hypovolemic shock (group III) presented positive bacteriological exams of the MLN, and this rate was 90% in the group of animals that did not receive this substance (group II) (p < .05). Escherichia coli was the bacteria identified most frequently in culture tests (92.8%). The villosities atrophy and inflammatory infiltrate of the lamina propria were the most common histological changes in the bowel, although the intensity was similar in groups II and III (p > .05), but more intense that in group I (p < .05). The mortality rates in groups I, II, and III 7 days after hypovolemic shock were 0%, 20%, and 20%, respectively. Prophylactic antibiotics significantly reduced the presence of bacteria in the MLN in situations of hypovolemic shock, in rats. This was probably related to a lower BT. However, this aspect did not modify the mortality rate of the animals. Also, the possibility that BT may not have a significant influence in this outcome should be considered.     

Role of bile in intestinal barrier function and its inhibitory effect on bacterial translocation in obstructive jaundice in rats

BACKGROUND: Our previous study using genetically labeled Escherichia coli strain JNW14 revealed that obstructive jaundice promotes bacterial translocation in rats and that the absence of bile in the intestinal tract is considered to be a factor inducing bacterial translocation. The aim of this study was to investigate the role of bile and bile acids in intestinal barrier function against bacterial translocation. MATERIALS AND METHODS: Eight-week-old male specific-pathogen-free Wistar rats were subjected to ligation of their common bile ducts (CBDL). The CBDL rats were treated with bacitracin, neomycin sulfate, and streptomycin sulfate, and the intestinal tract was colonized with E. coli strain JNW14, which was genetically labeled with resistant markers against the above three antibiotics, to monitor the bacterial translocation. The rats were then administered saline, cholic acid (20 mg/100 g BW), taurocholic acid (TCA: 5-50 mg/100 BW), or bile (1.5-6 mL/day) via a duodenal catheter. The degree of bacterial translocation of E. coli strain JNW14 to the mesenteric lymph nodes was compared. Histopathological examination of the terminal ileum and intestinal permeability test using phenolsulfonphthalein was also performed. RESULTS: Both cholic acid and TCA showed no inhibitory effect on bacterial translocation at any of the doses tested in CBDL rats, although TCA significantly decreased the numbers of E. coli strain JNW14 in the cecum. However, bile administration reduced the numbers of E. coli strain JNW14 in the cecum and mesenteric lymph nodes in CBDL rats although the inhibitory effect was weak. The integrity and permeability of the intestinal mucosa were kept at normal levels by bile administration in CBDL rats whereas the morphological changes, such as villous atrophy, villous edema, and lacteal canal dilatation, were observed in other CBDL rats. CONCLUSION: Bile plays an important role in maintaining the intestinal barrier function to prevent the invasion of enteric bacteria to the underlying tissues, suggesting that the intestinal administration of bile to patients with obstructive jaundice is a useful way to reduce infectious complications by inhibiting bacterial translocation from the intestine to other organs.     

Effects of the administration of pentoxifylline and prednisolone on the evolution of portal fibrogenesis secondary to biliary obstruction—an experimental study in growing animals

Background

Many chronic liver diseases lead to progressive hepatic fibrosis, a condition that can ultimately result in loss of organ function and severe portal hypertension necessitating hepatic transplantation. Within the last few decades, studies have been conducted to demonstrate the possibility of drug modulation of hepatic fibrogenesis. Regarding biliary obstruction, it has been suggested that administration of corticosteroids could promote better late outcomes for children with biliary atresia submitted to Kasai's portoenterostomy. Models used to test potential antifibrogenic drugs such as pentoxifylline (PTX) have not included growing animals.

Methods

In this experimental study, 119 young rats (21st or 22nd days) were submitted to laparotomy and common bile duct ligation (CBDL) or to sham surgery (SHAM). Animals were allocated into 5 groups, according to surgical procedure, and administered the following solutions: (1) CBDL + distilled water, (2) SHAM + distilled water, (3) CBDL + PTX, (4) CBDL + prednisolone (PRED), and (5) CBDL + PTX + PRED (PTX + PRED). Each group was further divided into 2 subgroups according to the length of the experiment (15 or 30 days). At the end of the defined period, animals were weighed, and a hepatic fragment was collected from each one for analyses.

Results

The PTX animals exhibited increased weight gain compared to animals in the PRED or PTX + PRED groups. Animals from the 3 therapeutic groups (PTX, PRED, and PTX + PRED) showed diminished collagen-filled area in portal spaces. Total portal space area was increased in the PTX group.

Conclusions

Hepatic fibrosis induced by bile duct ligation in young rats could be modulated by pharmacologic interventions. Administration of PTX or PRED, or the combination of both, resulted in diminished collagen-filled areas in portal spaces.     

去氢胆酸钠治疗阻塞性黄疸内毒素血症的实验研究

目的:观察去氢胆酸钠降低阻塞性黄疸时血清内毒素的效果。方法:将CD大鼠随机分成对照组、胆总管结扎组和胆总管结扎-胆盐治疗组,测定各组血清胆红素、免疫球蛋白IgG、IgM和内毒素。结果:胆总管结扎-胆盐治疗组血清内毒素明显下降（P<0．01）,血清免疫球蛋白IgG、IgM有较明显升高。结论:口服去氢胆酸钠可能有助于降低阻塞性黄疸的血清内毒素。     

Intestinal microbiota and innate immunity-related gene alteration in cirrhotic rats with liver transplantation

Background

The present study investigated the alteration of intestinal microbiota, innate immunity-related genes, and bacterial translocation in rats with cirrhosis and liver transplantation.

Methods

Specific pathogen-free Sprague-Dawley rats were randomized into 4 groups: (1) normal controls (N); (2) liver cirrhosis (LC); (3) normal control groups with liver transplantation (LTN); and (4) liver cirrhosis with liver transplantation (LTC). We examined plasma endotoxin, bacterial tacslocation, Denaturing Gradient Gel Electrophoresis (DGGE) profile of intestinal mucosa-associated bacteria, abundance of key bacterial populations, and expression of innate immunity-related gene.

Results

The LTC and LC group, showed higher endotoxin levels (1.08 ± 0.73 EU/mL and 0.74 ± 0.70 EU/mL, respectively) than the N group (0.27 ± 0.13 EU/mL; P < .05). the incidence of bacterial translocation (BT) to liver and mesenteric lymph nodes (MLN), and the number of total bacteria were increased significantly in the LTC and LC groups compared with the N group (P < .05). The counts of Lactobacilli and Bacteroides were lower, whereas Enterobacteria were higher in the LC than the N group (P < .05). Mucins (MUC2, MUC3) and Toll-like receptors (TLR2, TLR4) messenger RNA (mRNA) expression were significantly higher in the LC and LTC groups than the N group (P < .05). The marked difference between the groups in the overall structure of the bacterial community was also generated by DGGE profiles.

Conclusion

Liver cirrhosis disturbs intestinal microbiota and innate immunity-related genes, which contributes to endotoxemia and bacterial translocation. These had not completely recovered in cirrhotic rats until 1 month after orthotopic liver transplantation.     

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) recieved endotoxin (10 mg/kg intraperitoneally,n=9), while the control group (CONT,n=8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P<0.05), while the CVP and SMVP increased (P<0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P<0.05). The D-xylose concentration in SMV decreased significantly (P<0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.     

Obstructive Jaundice Alters Proliferating Cell Nuclear Antigen Expression in Rat Small Intestine

Translocation of bacteria and endotoxin has long been documented in obstructive jaundice, and altered intestinal barrier function is considered to be one of the important mechanisms for this phenomenon. Proliferating cell nuclear antigen (PCNA), also known as cyclin, is an auxiliary protein of DNA polymerase-, and the level of synthesis correlates directly with rates of cellular proliferation and DNA synthesis. This study was designed with the aim of evaluating the effect of obstructive jaundice on PCNA expression in small bowel epithelium. Male Sprague-Dawley rats were randomized to four groups. Group A (n = 10, control group) underwent a sham operation. Group B (n = 9, obstructive jaundice group for 1 week) underwent common bile duct ligation. Group C (n = 8, obstructive jaundice group for 2 weeks) underwent common bile duct ligation. Group D (n = 8, obstructive jaundice group for 2 weeks) underwent common bile duct ligation with oral glutamine intake. After periods of 7 days and 2 weeks, segments of small bowel were harvested from groups A & B and groups C & D, respectively. Nuclear immunohistochemical expression of PCNA in small bowel was evaluated. The PCNA-labeling index [(PCNA-positive cells/500 cells) × 100] was quantified. Comparisons among the four groups were performed. The PCNA-labeling index in small bowel of group B was significantly higher than that of group A (29.0% vs 21.2%, p = 0.001). After 2 weeks of common bile duct ligation, the PCNA-labeling index in small bowel of group C was significantly lower than that of group A (19.4% vs 21.2%, p = 0.045). With oral glutamine intake daily, the PCNA-labeling index in small bowel of Group D was restored and was significantly higher than that of group A (24.5% vs 21.2%, p = 0.002). Obstructive jaundice for 1 week upgraded PCNA expression in rat small intestine. PCNA expression in rat small intestine later became depressed after obstructive jaundice for 2 weeks. Oral glutamine intake daily could effectively restore the PCNA expression in small bowel of rats subjected to obstructive jaundice for 2 weeks.     

人参茎叶皂甙对梗阻性黄疸大鼠心肌损害的保护作用

目的 观察人参茎叶皂甙对梗阻性黄疸大鼠的心肌保护作用。方法 应用结扎Ｗｉｓｔａｒ大鼠胆总管的方法制作了梗阻性黄疸的动物模型,８０只大鼠分四个实验组：胆总管结扎组（ＣＢＤＬ组）、胆总管结扎加用腹腔注射人参皂甙组（ＢＤＬ－ＳＬＧ组）、手术对照组（ＯＣ组）、正常对照组（ＮＣ组）。每组２０只鼠,用电镜及光镜观察胆总管结扎术后３、７、１４、２１ｄ各组大鼠的心肌改变。结果 随着胆总管结扎时间的增加,心肌损害亦相应加重,电镜及光镜下心肌损害越明显,而ＣＢＤＬ－ＳＬＧ组的心肌为较与其相对应的ＣＢＤＬ各组的心肌改变明显减轻,术后７、１４、２１ｄ时,两组的肌节长度、密度、线粒体体积密度及线体表面积密度差异显著,Ｐ〈０．０１。结论 人参茎叶皂甙具有心肌保护作用,其作用机理为其具有生物膜保护作用。     

Changes of hepatic blood flow and intrahepatic microvascular bed in rats with chronic biliary obstruction]

The effective hepatic blood flow (EHBF) and intrahepatic microvascular bed (IMB) of rats were studied with hydrogen clearance and India ink perfusion 1, 2, 3 weeks after common bile duct ligation (CBDL). The EHBF decreased significantly in all 3 CBDL groups, compared to control (P < 0.0001). There was no significant difference among CBDL groups (P > 0.05). In a given group no significant difference was noted between the blood flow of the left lateral lobe and that of the middle lobe. The IMB was destroyed severely in all CBDL groups. It was concluded that when chronic biliary obstruction developed the EHBF decreased significantly because of shrinkage of IMB resulting from extensive fibrosis of the liver, and necrosis of liver cells.     

胆道梗阻时脱氧胆酸钠及乳果糖对小肠粘膜的影响

为观察外源性胆盐及乳果糖对小肠粘膜的影响，将２０只成年Ｗｉｓｔａｒ大鼠随机分为假手术组、胆管结扎组、胆管结扎＋胆盐治疗组和胆管结扎＋乳果糖治疗组，每组５只，２１天后处死动物，观察小肠粘膜的病理及四种酶活性的改变。结果：胆管结扎组小肠粘膜明显水肿，ＡＴＰａｓｅ、ＳＤＨ、ＡＫＰ活性明显减弱，Ａｃｐ活性明显增强；脱氧胆酸钠及乳果糖治疗组小肠粘膜未见异常或见轻度水肿，四种酶活性均较胆管结扎组有明显改善。提示，外源性胆盐及乳果糖对梗阻性黄疸时的小肠粘膜有保护作用。