The Change Of Intestinal Microecology In Rats After Liver Transplantation And Effects Of Lactulose Or Lactobacillus On It

Orthotopic liver transplantation is the best way to cure the end-stage liver disease such as acute or chronic hepatic failure and cirrhosis, and hepatic encephalopathy. The successful rate was increased and survival time was extended followed by workmanlike operation skill and emergency of new immunity inhibitor such as FK506, whereas infection and all kind of rejection were the main cause of the mortality of liver transplantation after or surround the surgery.Recent study showed that intestinal microecology and liver tie up closely not in anatomical structure but also in functional statue, they can influenced each other. It can exacerbate the injury of the liver and subsequently induce various complications. Otherwise the complexity of liver transplant surgery including hepatic cold and warm ischemia-reperfusion injury was inevitable in the liver surgery, It can affect body prodigiously. Hence the induction of the serious pathophysiology result. The current study was focus on the changes of intestinal microecology after liver transplantation on the basis of steady rat model. Method:Transplantation was performed using the techniques described by Kamada with additional rearterialization. All animals received no antibiotics before and after operation. All the procedure include surgery and sacrifice was under sterile condition. The study was divided into two parts: Party one: The change of Intestinal Microecology in Rats with Liver TransplantionRat were divided into four groups: control group(n=18), sham group(n=18), Isogenic liver transplantation: Isogeneic liver transplantation was performed in a rat combination of Brown Norway (BN to Brown Norway (BN) (n=18), Allogenic liver transplantion: Allogeneic liver transplantation was performed in a rat combination of Dark Agouti (DA) to Brown Norway (BN) (n=18).All animal received immunity inhibitor cyclosporine (CsA) by subcutaneous injection(1.0mg/kg/d), animals in Day 50 group received CsA(l mg/kg/d) from transplantation to day 15 once daily and every other day from day 15 to 30, the other rats received CsA till sacrificed.Specimen collection was performaned on the 1st, 7th and 50th day after liver transplantion(n=6 in each time spot), the rat were sacrificed and liver enzyme, cecum bacterial counts, bacterial transaction to other site, plasma endotoxin and ileum and liver mucosal histology were investigated. Result:The disturbance of intestinal microflora were observed in rat one day after liver transplantation, simultaneity the damage of the intestinal mucosal barrier, the translocation of bacteria, the elevation of plasma were also found. The unbalance of intestinal flora was alleviated after a period of time in isogenic liver transplantation group, whereas no remarkable improvement were observed in allogeniec liver transplantation group.Part two: Effects of Microecological Preparations on the Intestinal Microflora and Bacterial Translocation in Allogenic Rat Transplantation ModelExperiment design: Male inbred Brown-Norway(BN) and Dark Agouti(DA) were paired divided into three groups(control group, lactobacillus group and lactulose group), each group contain 12 donor rat and 12 recipients. Allogeneic liver transplantation performed in a rat combination of Dark Agouti (DA) to Brown Norway (BN) were used as control group which received 3ml sterile water by gavage from 7th day before surgery, while the lactobacillus group received probiotics (Lactobacillus reuteri ATCC 55730)which contain 4X 109 colony forming unit, and lactulose group were received 1 gram of the lactulose in the same way. Gavage last until the sacrificed of the animal except for the day of operation. All the animals received CsA(l mg/kg/d) by subcutaneous injection(l .Omg/kg/d) until sacrifice.Specimen collection was performaned on the 1st and 7th day after liver transplantion(n=6 in each time spot), the rat were sacrificed and liver enzyme, cecumbacterial counts, bacterial transaction to other site, plasma endotoxin and ileum andliver mucosal histology were investigated.Result:Pretreatment with lactulose or lactobacillus can both lowed the levels of the plasma endotoxin 24h after liver transplantation and reduce incidence of bacterial translocation to liver ^ spleen and kidney. In lactobacillus group showed a increase in lactobacillus counts and a decrease in Enterobacteriaceae and Enterococcus;Lactulose group showed a increase in lactobacillus and bifidobacterium counts, whearas no chang were found in the levels of Enterobacteriaceae and Enterococcus.Lactulose or lactobacillus can both lowed the levels of the plasma endotoxin 24h after liver transplantation and reduce incidence of bacterial translocation to liverN spleen and kidney. In lactobacillus group showed a increase in lactobacillus counts and a decrease in AST and TBiL;Lactulose group showed a increase in lactobacillus counts and a decrease in the levels of Enterobacteriaceae and Enterococcus, which associated with decreased liver function such as ALT\ AST and DBiL. Conclusion:The above result showed that disturbance of intestinal microflora was observed in rat with liver transplantation, simultaneity the damage of the intestinal mucosal barrier, the translocation of bacteria, the elevation of plasma endotoxin were also found. Supplemented with microecological preparations can decrease the levels of plasma endotoxin liver injury and the rate of bacterial translocation more effectively through improving intestinal microflora.