Liver regeneration (LR) is one of the key factors for the outcome of survival in those patients with hepatic tumor receiving partial hepatectomy, and liver cirrhosis received partial liver transplantation. LR is also one of the most rapid forms of tissue growth known in the mammals. A rat model of two-thirds partial hepatectomy (PH) followed with quick LR was created by Higgins GM and Anderson RM in 1931. Using this model, many factors were reported to affect LR. Nutrition was proved to be one of the most important factors which affecting the degree of LR.
　　Among the indicators of LR after two-thirds PH, the remnant liver weight/body weight (RLW/BW) ratio increased soon, up to near 90% of the original volume at 72h after PH. The DNA synthetic rate increased significantly at 24h, mitotic index of hepatocytes increased significantly at 48h, and the total DNA amount in the remnant liver increased quickly during the early 72h after PH. Ultrastructures of hepatocyte under electron microscope revealed that the glycogen disappear with decrease of rough endoplasmic reticulum (RER), increase of smooth endoplasmic reticulum (SER), lysosome, and lipid accumulation at early stage after PH. Glycogen soon reappeared, with a zigzag nucleus membrane was noted at 24h, lipid became more and bigger with some RER dilatation were demonstrated at 72h after PH.
　　Energy substrate (High energy, phosephate, CP and ATP) was found to decrease markedly at early stage during LR after PH. Whether glucose or fatty acid is the major energy substrate was controversial. We measured LR indicators (RLW/BW ratio, DNA synthetic rate, total DNA amount, and mitotic index) in high-glucose (HG) or high-fat (HF) i.v. infusion rats which PH was performed. The results demonstrated that HG rats have a better LR than HF rats. Fatty acid was utilized only at very early stage after PH. Glucose is predominant for the remnant liver during LR. The carnitine level in serum, remnant liver, kidney, and skeletal muscle, and the carnitine palmitoyltransferase-1 (CPT-1) activity in remnant liver were measured. We found that influx of carnitine into hepatocytes from kidney and skeletal muscle guarantee a sufficient carnitine content in remnant liver. The mitochondrial respiration with CPT-1 effect could be the factor for this energy substrate utilization.
　　The role of amino acid, especially branched-chain amino acid (BCAA), was proved to have benefits on LR. We compared the LR indicators in high-BCAA (HB) or normal-BCAA high amino acid (NB) i.v. infusion rats which received PH, and found that HB rats have a significantly better LR than NB rats. BCAA may increase LR through a better intra- and extra-hepatic metabolism, providing exogenous amino acid demands, co-enzyme effect, stimulating branched-chain amino transferase (BCAT) and hepatocyte became more and bigger with some RER dilatation were demonstrated at 72h after PH.
　　Energy substrate (High energy, phosephate, CP and ATP) was found to decrease markedly at early stage during LR after PH. Whether glucose or fatty acid is the major energy substrate was controversial. We measured LR indicators (RLW/BW ratio, DNA synthetic rate, total DNA amount, and mitotic index) in high-glucose (HG) or high-fat (HF) i.v. infusion rats which PH was performed. The results demonstrated that HG rats have a better LR than HF rats. Fatty acid was utilized only at very early stage after PH. Glucose is predominant for the remnant liver during LR. The carnitine level in serum, remnant liver, kidney, and skeletal muscle, and the carnitine palmitoyltransferase-1 (CPT-1) activity in remnant liver were measured. We found that influx of carnitine into hepatocytes from kidney and skeletal muscle guarantee a sufficient carnitine content in remnant liver. The mitochondrial respiration with CPT-1 effect could be the factor for this energy substrate utilization.
　　The role of amino acid, especially branched-chain amino acid (BCAA), was proved to have benefits on LR. We compared the LR indicators in high-BCAA (HB) or normal-BCAA high amino acid (NB) i.v. infusion rats which received PH, and found that HB rats have a significantly better LR than NB rats. BCAA may increase LR through a better intra- and extra-hepatic metabolism, providing exogenous amino acid demands, co-enzyme effect, stimulating branched-chain amino transferase (BCAT) and hepatocyte growth factor (HGF) effect.
　　As for the hormone effects, we gave single or combined insulin, glucagon, and epidermal growth factor (EGF) by subcutaneous injection. The results demonstrated that any one single hormone administration has no obvious effect on LR, however, combination of insulin and glucagon, or three combine of insulin, glucagon, and EGF can increase LR significantly.
　　About immune effects, we demonstrated that the spleen weight/body weight ratio increased with an expansional white pulp due to lymphoid aggregation and a narrowing red pulp at 48h after PH. Scan electron microscope also demonstrated that the morphology of lymphocyte changed markedly with increasing folds, filaments, microvillus in the cell surface, with marked daughter masses formation produced. While measuring white blood cell, absolute lymphocyte, T3, T4, T8, natural killer (NK) cell counts, serum levels of gamma-interferon (γ-IFN), interleukin-2 (IL-2), interleukin-2 receptor (IL-2R), and the remnant liver NK cells, we demonstrated that cell-mediated immunity is induced markedly during LR after PH. The variation of neopterin, a small molecular released from activated macrophage by γ-IFN stimulation, revealed a marked increase both in serum and urine. Immune reaction might play as an important role during termination of LR. We furthermore gave the immunosuppressants, either cyclosporine A (CyA) or FK506, to the PH rats, and investigated the ODC contents and Brd U incorporated index as LR indicators in the remnant liver. The results demonstrated that either CyA or FK506 administration can increase the degree of LR.
　　As for the genetic control pathway which should also play a key role to affect the LR after PH, we have detected the variations of nutritional related genes such as, immune related gene (Interleukin 6, IL6), angiogenesis related gene (Angiotensinogen, Agtn), and apoptosis related genes (Myeloid cell leukemia-1, Mcl-1) expressions by cDNA microarray, their mRNA expressions by Q-PCR, and their protein products by Western Blot and immunohistochemical stain. The results demonstrated a possible correlation pathway between nutritional related genes expressions and LR process. These genes may play as important roles in gene-regulated pathway during LR although the detailed mechanism remains unclear.
　　Conclusions: Nutritional factors can affect the degree of LR after PH. The energy substrates including glucose, fatty acid, BCAA are important for LR. Hormone combination of insulin, glucagon, and EGF can up-regulate LR. Immunosuppressants, CyA and FK506, were proved to be able to increase LR. As for genetic nutrition, further study should be necessary to clarify the role of nutritional related genes, their regulation pathways and the mechanism for LR after PH.