【Abstract】ObjectiveTo explore the effect of glutamine on immune function of rat with obstructive jaundice and its possible mechanism. MethodsFifty male Wistar rats were randomly divided into three groups: Control group (n=10)， obstructive jaundice group (n=20) and glutamine treatment group (n=20). The serum concentration of TNF-α, IL-10 was detected by using radioimmune method. Liver function was measured through automated biochemistry analyzer. The animal model of obstructive jaundice was established by ligating the rat’s common bile duct. Bacteria cultures were performed with the rat’s tissues of lung, spleen, liver and kidney respectively. ResultsCompared with control group, obstructive jaundice group showed statistically lower serum level of TNF-α, and statistically higher serum level of IL-10, TBIL, ALT and AST during the first and the second week after ligation of common bile duct. During the first and second week after administration of glutamine, the serum TNF-α of glutamine treatment group was statistically higher than that in control group and obstructive jaundice group. Meanwhile, glutamine treatment group showed statistically lower serum level of IL-10, TBIL, ALT and AST than obstructive jaundice group. There were statistically less bacteria translocations in glutamine treatment group than those in obstructive jaundice group. Conclusion Glutamine can increase the immune function by changing serum concentration of TNF-α, IL-10 and decrease the bacteria translocation.
Objective To investigate the changes and significance of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in intestinal mucosa in rats with obstructive jaundice. MethodsTwenty-four SD rats were randomly divided into sham operation (SO) group and bile duct ligation (BDL) group, and each group were randomly divided into the day 7 and day 14 subgroup. The expression of ICAM-1 was assayed by immunohistochemistry. The level of TNF-α was determined by ELISA. The activity of myeloperoxidase (MPO) and diamine oxidase (DAO) was determined as well.ResultsOn the day 7 and 14, in the bile duct ligation group, the ICAM-1 protein was mainly expressed in the intestinal epithelia and increased with the time on (P＜0.05); the level of TNFα increased from （14.25±1.01） ng/g to （23.83±1.43） ng/g （P＜0.01）； the intestinal DAO activity decreased from （1.70±0.36） U/mg to （1.22±0.41） U/mg （P＜0.01），and plasma DAO activity increased from （6.44±1.74）U/ml to （8.93±1.29） U/ml （P＜0.01）; the MPO activity increased from （2.85±1.22 ） U/mg to （4.93±1.37） U/mg （P＜0.01）. ConclusionThe ICAM-1 expression is significantly upregulated and the level of TNFα significantly increases after bile duct ligation, which may be involved in the PMNmediated injury to intestinal mucosa.
ObjectiveTo investigate the change of renal endothelin (ET) excretion and its relation to renal dysfunctions in obstructive jaundice.MethodsSixty male Wistar rats were randomized into two groups, the common bile ducts were ligated to establish the model of obstructive jaundice in experimental group, and only sham operation was done in control group. Ten rats were taken from each group at 5, 10 and 15 days respectively after operation, renal functions were evaluated by paminohippuric acid clearance (CPAH), inulin clearance (CIN) and fractional sodium excretion (FENa+); furthermore, plasma endotoxin (EX) level was determined, and ET1 contents in renal arterial plasma, renal venous plasma and renal tissue were detected. ResultsOnly FENa+ was significantly increased at the 5th day in experimental group; since the 10th day, all the three renal functional parameters gradually decreased, and FENa+ was significantly lower than that in control group at 15th day (P＜0.01 vs control). ②The plasma EX sustained at significantly higher levels after operation in experimental group (P＜0.01 vs control). ③The renal arterial plasma ET1 was significantly decreased, while the contents in renal venous plasma and renal tissue were significantly increased after operation in experimental group (P＜0.01 vs control). ④There were positive correlation between plasma EX and renal ET1 content, negative correlation between renal ET1 content and CPAH/CIN, and positive correlation between renal ET1 content and FENa+ (P＜0.01).ConclusionThe increased excretion of renal ET stimulated by endotoxemia may play an important role in the renal dysfunctions in obstructive jaundice.
ObjectiveTo study the change and significance of the serum nitric oxide (NO) level in patient with obstructive jaundice complicated with renal dysfunction. MethodsThe level of NO, BUN, Cr in serum and the activity of NOS in 25 patients with obstructive jaundice and renal dysfunction and 26 healthy adults was studied.ResultsThe patients’ serum NO level and the activity of NOS were significantly lower than those in the control group(P＜0.01)，whereas the serum BUN and Cr levels were significantly higher than those in control group(P＜0.01). The linear correlation analysis showed that the serum NO had a negative correlation between serum BUN and Cr level (P＜0.01). ConclusionThe patients with obstructive jaundice and renal dysfunction may lead to the decrease of serum NO level. NO may have some protective effects to the renal function during obstructive jaundice.
Objective To explore the regulating mechanism of hepatic injury in obstructive jaundice (OJ). Methods①Rat hepatocytes were isolated by in situ collagenase perfusion and primary culture. Hepatocytes were pretreated with various concentrations of protein kinase C (PKC) agonist parsmeae (PMA) and inhibitor chelerythrine for 20 min. After pretreatment, 50 μmol/L glycochenodeoxycholate (GCDC) was added. Cells were next detected by FCM and TUNEL.②Experimental obstructive jaundice was induced by double ligation of the bile duct (BDL), BDL for 3, 7, 14, 21days.We detected apoptotic status in liver with TUNEL and PKC protein in liver with immunohistochemistry method. Results①PMA increased GCDCinduced apoptosis and chelerythrine decreased GCDCinduced apoptosis in a concentrationdependent manner. ②The apoptotic rate of liver was related to time of OJ. Apoptosis index (AI) was the highest in 14day bile duct ligation. The ber PKC expression, the more number of apoptotic cells in OJ.Conclusion PKC takes part in the regulation and the occurrence and progression of hepatic injury in OJ.
Objective To investigate the pathological characteristics of hepatic energy metabolism changes following hepatic inflow occlusion and the tolerant limit to ischemia in cholestatic rats.Methods On the day 7 after rats biliary obstruction, the survival rate, hepatic mitochondrial respiratory function, content of ATP, and the ketone body ratio in arterial blood were investigated following the different duration of hepatic ischemia and reperfusion with portal blood bypass.Results The survival rate on postoperative day 10 was 100%, 100% and 40% subjected to 30, 60 and 90min of hepatic vascular occlusion. The hepatic energy metabolic function was decreased markedly following ischemia, and was increased markedly on 24 hours following reperfusion subjected to 30, 60min of hepatic vascular occlusion, but it had less increase with 90min of hepatic vascular occlusion.Conclusion The hepatic energy metabolic function injury is reversible in cholestatic rats, and the rats can tolerate hepatic inflow occlusion within 60min, but the hepatic energy metabolic function injury is irreversible after 90min of hepatic occlusion.
Objective To investigate the effects of cimetidine on the red cell immune function and interleukin-2(IL-2) in rats with obstructive jaundice. Methods Sixty SD rats were divided into bile duct ligation(BDL) group, cimetidine therapy (BDLC) group and sham operation(SO) group respectively. The red cell immue function and serum IL-2 level were determined with the red cell yeast-rosttes test and radioimmunoassay respectively. Results The red blood cell C3b receptor rosette rate(RBC-C3bRR), the red blood cell immune complex rosette rate(RICR), the red blood cell C3b receptor rosette-forming excited rate(RFER) and serum IL-2 level were significantly lower in BDL group as compared with SO group, the red blood cell C3b receptor rosette-forming inhibitory rate(RFIR) in BDL group was higher than that of SO group. After 7 days’ cimetidine therapy RBCC3bRR, RICR, RFER and IL-2 became higher than those of BDL group, but RFIR was lower than that of BDL group. Conclusion Supplemental cimetidine can significantly enhance the impaired red cell immune function and IL-2 production in rats with obstructive jaundice.
Objective To research the changes in plasma endothelin, LPS, TNF-α, IL-6 and IL-8 in the patients with obstructive jaundice (OJ) and non-obstructive jaundice (NOJ) after surgery. Methods The plasma ET, LPS, TNF-α, IL-6 and IL-8 were measured in 15 patients without jaundice as controls. Results As compared with NOJ, the postoperative changes of ET, LPS, TNF-α, IL-6 and IL-8 in OJ group increased significantly at multiple time points (P＜0.05). Conclusion There is interaction between ET,LPS, TNF-α, IL-6 and IL-8 and damage to multiple organ function in patients with OJ after surgery.
Kupffer cell phagocytic function and plasma endotoxin level in 36 patients with obstructive jaundice were observed. The results indicated that kupffer cell phagocytic function was inhibited and the plasma endotoxemia level was markedly increased as compared with those in the control group Ｐ＜0.05 and Ｐ＜0.01 respectively. Kupffer cell phagocytic function were recoverd and plasma endotoxemia alleviated while the biliary obstruction was released by surgery.
In order to study the immune function of patients with obstructive jaundice, the rate of RBC-C3b receptor rosette (RCR), tumour-RBC rosettes (TRR), RBC-immune complex rosette (RICR) and CD３+,CD4+,CD8+ cells were investigated. In these patients, the pre-operative erythrocyte and T lymphocyte subsets immune functions were lower than those of the control (Ｐ＜0.001). At the 5th day after operation, there was no significant change and 14th day after operation the erythrocyte and T lymphocyte substes immune functions were significantly elevated(Ｐ＜0.05), while, compared with the normals, which was still depressed in some degree. Operation is useful to the recovery of the immune function in all patients.