The Study Of Rapamycin On The Liver Protective Effect In Rats With Obstructive Jaundice

Objective:The common bile duct was ligated to establish model of obstructive jaundice, After the establishment of the model, the rats were injected RPM, one time for every day. Through research the changes of liver cell structure and function, the expression of correlated inflammatory factors and their interrelationship of different period, observe pathological changes and the mitochondrial structure changes of rat liver cell, detecte the expression of TNF-a mRNA, To investigate the protective effect of Rapamycin on the rats’liver with obstructive jaundice. Provide a theoretical basis and technical path to reduce the hepatic injury for clinic.Methods:1experimental groups:54healthy male Sprague-Dawley rats were randomly divided into3groups,18of each group and6of each period. Group A:After anesthesia is successful, take the median incision of epigastrium, dissect and separate the common bile duct, then close the abdomen; Group B:After anesthesia is successful, The common bile duct was ligated to establish model of obstructive jaundice, After the establishment of the model, the rats were injected0.4mg/kg RPM, one time for every day; Group C:Modeling methods was same with group B, and injecteng saline at the same time. The rats were sacrificed after1,3and5d,6for each time period.2Compare the index changes of rat in different time periods:The rats were killed1d、3d、5d after operation, cut liver median lobe and extract the inferior vena cava blood as samples, detect serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), the content of endotoxin(ET), malondialdehyde (MDA) and superoxide dismutase (SOD) levels of liver, analysis the expression of TNF-a mRNA by Reverse Transcription-Polymerase Chain Reaction(RT-PCR), The specimen of liver were collected to make the pathological analysis.Results:1The standard of successful operation is after operation, rats can regained consciousness and stood up immediately, and maintain effective breathing and heartbeat. 2Changes of serum ALT、AST and ET levels:serum ALT and AST levels are sensitive clinical indexs that can reflect the degree of liver cell injury and necrosis, and Endotoxin levels can reflect inflammatory changes.c in the same time periods ompare with group A, serum ALT、 AST and ET levels of group B and group C were significantly increased (P<0.01).Compare with group C, serum ALT、AST and ET levels of group C were significantly lower (P<0.01).3Changes of liver tissue MDA and SOD levels:MDA can reflect the degree of lipid peroxidation and indirectly reflect the degree of cell injury; SOD is oxygen free radical scavenger, can indirectly reflect the level of oxygen free radicals level and the injury degree of lipid peroxidation. Compare with group A, the liver tissue MDA level of group B and group C increased, while the SOD level decreased, the difference is significant (P<0.01); compare with group C, liver tissue MDA level of group B were significantly decreased, and SOD level significantly rised, the difference is significant (P<0.01).4TNF-a mRNA content of liver tissue:Compare with group A, TNF-a mRNA content of group B and group C was significantly higher (P<0.01). Compare with group C, TNF-a mRNA content of group B was significantly decreased (P<0.01).5Liver tissue histopathological changes of HE stain:The liver cells of group A were normal, the hepatic lobule, central vein, portal area structure is clear, and liver cell cord in order. The hepatic sinusoid was expantion, biliary ducts accrementition and dilation, more inflammatory cell infiltrated, and the liver cells were swelled.With time prolong, compare with group B, The expantion of hepatic sinusoid, the cholestatic of hepatic lobule, the liver cells swelled and morinflammatory cell infiltrated was obviously in group C, there was increasing collagen fiber, hepatic lobules Structure were damaged, even complete cirrhotic nodule, there was extensive increasing collagen fiber in portal areas, liver cell necrosis was obviously, and infarction with bile overflow.ConclusionThere are many factors leading to endotoxemia when obstructive jaundice, and toxemia can result in significantly higher TNF-a expression, Rapamycin by inhibiting the JAK/STAT signal transduction pathway can inhibite the liver tissue of TNF-a expression, increasing the activity of SOD, decrease MDA content, which helps to prevent obstructive jaundice caused by uncontrolled inflammatory reaction induced liver injury. This may be rapamycin has protective effects on the liver in rats with obstructive jaundice.