Establishment Of Jaundice Model In The Canine And The Effect Of Unbinding The Bilirubin And Albumin Compound Before Absorption On Removal Of Bilirubin By CA/PEI Membrane

Objective: In order to increase the rate of absorption of jaundice serum bilirubin(BIL) by the CA / PEI membrane, this experiment for the first time applied the method of unbinding the BIL and albumin(ALB) compound before absorbed by CA/PEI membrane. We produced the models of cholestatic and hemolytic jaundice in mongrel dogs to get the jaundice serum and to compare the changes of the concentration of total bilirubin (TB), conjugated bilirubin(CB), non-conjugated bilirubin(UCB) and ALB before and after the experiment, aimed to investigate the unbinding effect on removing BIL by CA/PEI membrane.Methods:1.Establishment of cholestatic jaundice canine model: 2 adult dogs were selected. TB, CB, ALB and TBA basis concentrations were measured res- pectively using bromocresol green method, vanadate method and enzymatic cycle method. One underwent bile duct ligation, the other received bile duct - inferior vena cava bypass. They were raised as usual, given anti-inflame- matory treatment, and their concentrations of BIL were monitored after operation. Collected the jaundice serum from the former dog once every other day (30ml each time, total 8 times). Collected that of the latter dog once a day (30ml each time, total 6 times).2.Building of canine model of hemolytic jaundice: 2 adult dogs were used.TB, CB, ALB and TBA basis concentrations were measured respect- tively using above methods. Injected standard BIL solution at 3mg/kg and 5mg/kg respectively and after that, got the jaundice serum at 30, 60, 90 minutes, 30ml each time.3.Divided jaundice serum into three groups: A, for control group, B, for static absorption of BIL 2 hours by CA/PEI membrane, and C,for static absorption of BIL 2 hours by CA/PEI membrane after unbinding. The indexes above were measured again after absorption, then compared the changes of the clearance rates of TB, CB and UCB between B and C groups, and identified the relationship between the TB clearance rate and the concentrations of TB or ALB.Results:1.The cholestatic jaundice canine model could be successfully established by bile duct ligation and bile duct-inferior vena cava bypass. The concentration of BIL in the former model showed upward-flat- downward tendency, the peak of TB concentration was 134.9μmol/L after 12 days and the concentration of BIL fell to normal level after 28 days. The dog was in good condition with no complications. The concentration of BIL in the latter model increased rapidly in a short time and the concentration of TB reached 201μmol/L after 6 days. However, the dog was in poor condition and died after a week. The hemolytic jaundice canine model could be built by injection of BIL solution. The concentration of BIL in the high-dose group was higher than that in the low-dose in the same period, especially UCB increased significantly. The concentrations of TB could go up to 105.8μmol/L and 209.2μmol/L respectively in the two groups.2.The influence of unbinding on the removal of BIL in cholestatic jaundice serum: Both B and C groups showed a significant clearance of BIL. Compared with B group, C group showed more significant effects on removing TB and UCB (P<0.01), but there was no obvious difference on the clearance rate of CB (P>0.05). There was a positive correlation between the clearance rate of TB and TB concentration in both B and C groups, respectively r=0.906 and r=0.932.There was a negative correlation between TB clearance rate and ALB concentration in B group, r=-0.624, but no correlation was found in C group. The concentration of TBA significantly increased in C group (P<0.01). 3.The effect of unbinding on the removal of BIL in hemolytic jaundice serum: B and C groups showed a significant clearance of BIL. Compared with B group, C group showed more significant effects on removing TB and UCB (P<0.01), but there was no obvious difference on the clearance rate of CB (P>0.05).There was a positive correlation between the clearance rate of TB and TB concentration in both B and C groups, respectively r=0.966 and r=0.962. There was a negative correlation between the clearance rate of TB and ALB concentration in B group, r=-0.816, but no correlation was observed in C group. The concentration of TBA significantly increased in C group (P<0.01).Conclusion:1.The cholestatic jaundice canine model could be successfully established by bile duct ligation and bile duct-inferior vena cava bypass. The former was simple to be built without side effects to the dog, but there was a possibility of recanalization. The latter was relatively complex to be made with a poor tolerance, but the jaundice occurred rapidly. Injection of BIL solution could cause hemolytic jaundice model in the dog in a short time.2.Compared with absorption by CA/PEI membrane only, the unbinding compounds of BIL and ALB applied before absorption showed better effects on the clearance of TB and UCB in both cholestatic jaundice and hemolytic jaundice serum,while the effect was not influenced by the concentration of ALB. Meanwhile, a new issue that the concentration of TBA increased significantly with the addition of sodium deoxycholate was brought up and further study would be necessary.