| IntroductionThe technique development of reduced-size, split liver, and living-donor liver transplantation has widened the indication of clinical liver transplantaion and significantly relieved the crisis of donor organ shortage. But there are still some pivotal problems need to be resolved, such as graft function, size-adaption, ischemia-reperfusion injury, utility of immunosuppressor, and regeneration of the small size graft, which obstacle the development of small-for-size liver transplantation. As we all known, liver has an almost unlimited capacity to regeneration after the loss of hepatic tissue. The last century have brought a better understanding of signal transduction in liver regeneration. Most studys of liver regenerations are based on partial hepatectomy. It is still known scarcely about the mechanism of signal transduction in the graft undergoing small-for-size livertransplantation. Growth Hormone (GH) as a member of a large class of evolutionary related protein hormones was separated from the pituitary gland in 1920s. GH elicits various effects in vivo including postnatal growth and the regulation of lipid, carbohydrate, nitrogen, and mineral metabolism. It is anabolic in nature, promoting lipolysis and an increase in lean muscle mass. Due to such important physiological functions, GH has been widely used in clinical patients suffered severe bum, seriously surgical infection, trauma and operation. The ability of liver regeneration regulator of GH has been focused on recently. It's reported that the procedure of hepatocyte proliferation and liver regeneration can be affected by GH via regulating gene expression, enzyme activity, and the growth factor expression. MAPK families play an important role in complex cellular programs such as proliferation, differentiation, development, transformation, and apoptosis. There are three MAPK families have been characterized at least: extracellular signal-regulated kinase (ERK), Jun kinase (JNK/SAPK) and p38 MAPK. GH elicits its pleiotropic effects by binding to the GH receptor (GHR). Janus kinase-2(JAK2), a cytoplasmic tyrosine kinase is found associated with the GHR. JAK2/STATs is the most important signal transduction pathway activitied by GH/GHR. Furthermore, GH/GHR has been shown to induce tyrosine phosphorylation of insulin receptor substrate-1 and -2(IRS-1 and IRS-2) as well as She, Grb2, Sos,Ras, located in several animal tissues and cultured cell lines. GH also has been shown to activate both the PDK and MAPK/ERK signaling cascades. But till now, the exact mechamisms of MAPK signal transduction via rhGH/GHR in liver regeneration after small-for-size liver transplantation remain an active area of research. This study observed the liver function (ALT, ALB), ratio of liver regeneration, and estimated the expression of cytokines, cyclin-related proteins, and activition of MAPK in serum or/and in livertissue, and investigated the relationship between the MAPK pathway and rhGH.Materials and methodsObjectives: Male Wistar rats were used for the study (weight 200-230g). Methods: The experimental rats were divided into four groups randomly. Group A: sham operation; Group B: 60% hepatectomy (hepatectomy group); Group C: 40% small-for-size liver transplantation+salin treatment (salin group); Group D: 40% small-for-size liver transplantation+rhGH treatment (rhGH group). Rats in group D were administed rhGH subcutaneous 1IU/kg/d; group C were administed salin subcutaneous 1ml/kg/d. Rats were sacrified at the day 1,3,5,7 after operation. The wet regenerated grafts were weighted immediately, the ratio of liver regeneration was calculated, and ALT, ALB in serum were analyzed. Liver specimens of rats were observed under light and electron microscopy. Immunohistochemistry of PCNA and TUNAL were detected in paraffin sections of liver tissue. The level of IL-6, TNF- a and TGF- B in serum were analyzed with ELISA. The mRNA expression of IL-6, TNF- a , TGF- B , GHR, and IGF-1 in liver tissue were analyzed by RT-PCR. Western blotting was used to detect th...
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