| Total parenteral nutrition (TPN) is a life-saving therapy for patients with intestinal failure. But prolonged parenteral nutrition is associated with complications affecting the hepatobiliary system. Total parenteral nutrition (TPN)-associated liver disease (PNALD) is one of the well-recognized complications of this nutritional support. Although many pathogenesis have been suggested to be responsible for it, the pathophysiology of PNALD is still unclear. The aims of this study were to identify potential hepatocyte genes which may be either increased or decreased in expression during the administration of TPN with a real time PCR array.1. The alteration of cell cycle gene expression caused by TPNObjective: To identify the potential liver cycle genes, which may be either increased or decreased in expression during the administration of TPN, with a real time PCR array.Material and methods:12 male SD rats, weighting 225～250g ,special pathogen free , were housed in metabolic cages and subjected to an acclimatization period of a week. They were fed standard rat chow and had access to tap water ad labium. Rats were maintained under a 12-hr light-dark cycle at a temperature of 22?C and a relative humidity of 40% to 60%.The rats were randomized into two groups. The control group (N=6) and the TPN group (N=6).Total parenteral nutrition group received continuous TPN infusion through a silastic catheter inserted in the right jugular vein and the control group infusion the same physiologic saline by the same way. After 7 days, we used real time PCR array to analyze the differential expression of the cycle genes between the two groups.Results:(1)Two groups were found to have gained weight on the last experimental day compared with the beginning of the experiment. The weights in the control group were higher than those in the TPN group.(2)The TPN group was found to have large lipid droplets with unclear margins in the perilobular region and smaller lipid droplets in the centrilobular regions. One case was found necrosis. The control group was not found obvious change.(3)Control group liver was not found change at the electron microscope, but the TPN group was found the distension of liver blood sinus and cholangiole, diluvium of microvillus, the color of mitochondrial matrix obviously deep, chromatin margination and several apoptotic bodies. (4) There is no obvious change of bilirubin between the two groups, but AST of TPN group is higher the other. (5) The up-regulation live cycle genes of TPN group are Atm,Brca1,Cdkn1b,Dnajc2,G2a,Nfatc1,Notch2,Pkd1,Ppp2r3a ,and down-regulation cycle genes are Cdc25b,Ccnd1,E2f1,Mcm3,Nek2,Wee1.Conclusion: TPN lead to significant alternations in the cycle gene expression of liver. There are alterations in several the cycle genes. These alterations may be directed associated with the development of PNALD.2. The alterations of inflammatory cytokines & receptors gene expression caused by TPNObjective: To identify the potential liver inflammatory cytokines & receptors gene, which may be either increased or decreased in expression during the administration of TPN, with a real time PCR array.Material and methods: The same to the first part.Results: All the results are the same to the first part except the gene alterations. (2)The up-regulated liver Inflammatory Cytokines & Receptors genes of TPN group are C5/C5a,Ccl21b,Ccl25,Ccl3,Ccl7,Ccr1,Ccr2,Ccr3,Ccr5,Ccr6,Cx3cl1,Cx3cr1,Cxcl1,Cxcl5,IL-10,IL-10Rα,IL-11,IL-13ra1,IL-18,IL-1β,IL-1f5_predicted,IL1f6_predicted,IL-1r1,IL-1r2,IL-2Rβ,IL-2rγ,IL-8rβ,Itgam,Itgb2,Ltb,Cxcl4,TGF-β1,TNF,Tnfrsf1b,CD40Lg. The and down-regulated liver Inflammatory Cytokines & Receptors genes are CcL22,CcL24,IL-17b,IL-1a,IL-6rα,Mif.Conclusion: TPN lead to significant alternations in the gene expressions of the inflammatory cytokines and receptors of the liver, which may give insight into the potential mechanism of PNALD.
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