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Establishment of the Model of the Acute Rejection in Rat Liver Transplantation

Author: YinJun
Tutor: QianHaiZuo
School: Suzhou University
Course: General Surgery
Keywords: Liver transplant Rat model Acute rejection
CLC: R-332
Type: Master's thesis
Year: 2007
Downloads: 64
Quote: 0
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Abstract


Background With the development of surgical techniques and strong and effective clinical application of immunosuppressive agents, liver transplantation has become the treatment of chronic end-stage liver disease, acute liver failure and other diseases treatment. Clinical liver transplantation technology development depends on a large number of animal studies, experimental rats because of its low price, clear genetic background, feeding and management simple and controllable making it the first choice of many experimental animals. Rat liver transplantation model to study liver transplant organs to save ischemia - reperfusion injury, hemodynamic, immunosuppressants, graft rejection response and immune tolerance ideal animal model. Since 1973 Lee [1,2] for the first time establish a rat liver transplantation model, after 30 years of improvement of many Chinese and foreign scholars, now improved Kamada \In rat strain selection, the foreign inbred rats, such as: Lewis-BN, DA-Lewis, PVG-Lewis and other domestic wide selection of closed colony SD inbred rodent species, price and many other factors, most use Wistar rats for transplantation. Objective To establish a rat orthotopic liver transplantation acute rejection model, verify that the donor BN rats receptor combination rejection strength for the liver transplant rejection or immune tolerance in Lewis rats experimental research model and experimental basis . ⑴. Inbred rat liver transplantation model in the Lewis-BN; ⑵ after rats were randomly divided into two groups: the experimental group (n = 15), after the special intervention; controlled in accordance with the modified Kamada law established group (n = 15) after 7 days of FK506 0. 2mg / (kg · d) orally. Postoperative 4,7 and 10 days in each group were sacrificed 3, serum samples were collected liver specimens, the rest of the serum samples obtained via the tail vein blood; ⑶. Survival of the remaining six BN rats observed in each group; ⑷. Would HE staining of liver tissue specimens of each group after the light microscope pathological changes; ⑸. each group collected serum samples from liver function testing; (6) ELISA assay of serum γ-interferon (IFN-gamma) interleukin -10 (IL-10) content; ⑺ immunohistochemistry SP method to detect IFN-γ in the liver tissue IL-10 expression; ⑻ TUNEL assay hepatocyte apoptosis; Results ⑴ After the experimental period of preparation of 100 cases the familiar rat liver transplant and complement each other, we practiced a total of 32 cases of Lewis-BN rats liver transplant surgery, surgical success rate was 93.8% (30/32); ⑵ experimental group after BN rats 7 days after the die-offs, the median survival time of 9 days, corresponding deterioration of liver function: transaminases, bilirubin elevated albumin decline - severe immune rejection in transplantation of liver tips; while FK506 treatment the BN rat median survival period of 51 days, was significantly longer (P lt; 0.05) compared with the BN rat liver function in experimental rats, pathological prompts obvious or mild rejection; ⑶ postoperative 7, 10 days, the experimental group BN rat serum IFN-γ content was significantly higher than the preoperative and the control group (P lt; 0.05), transplanted intrahepatic also showed positive expression, while high IL-10 in the control group expression was significantly higher than the preoperative and the experimental group (P lt; 0.05). Hepatocyte apoptosis (4) the experimental group than FK506 intervention group significantly. Conclusion ⑴ nearly inbred Lewis rats as donors, the BN rat the receptor combinations acute rejection strong and stable, ideal rat-liver transplant acute rejection model; the ⑵ skilled operative, a fine micro-surgical techniques, effective anesthesia and perioperative management is the key to successfully established a rat liver transplantation model; ⑶ serum IFN-γ, IL-10 different levels of expression helps rats occurrence of acute rejection after liver transplantation diagnosis.

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