| Background: Living-related liver transplantation was developed to significantlyimprove clinical outcomes owing to the scarcity of cadaveric grafts. The size of thegraft is a major risk factor in adult-to-adult living donor liver transplantation. At theearly phase, living-related liver transplantation technology was mainly used in adultto children liver transplantation; the main advantage was not only safe operation fordonor and donor volume was well adapted to the functional requirements of thechildren receptor. Due to the higher requirements of the adult donor weight and thehigher risk of donor surgery, development of adult living donor liver transplantationwas limited. Coagulation disorders, ascites, hepatic encephalopathy, cholestasis, andischemic injury in pathological changes were typical characteristics of postoperativeliver graft function failure.The criteria of small-for-size liver graft involved two evaluation standard，GR/WR(graft weight/body weight)<0.8%and GV/SLV（graft volume/receptorstandard volume）<40%. The ischemic reperfusion injury was inevitable and mightplay an important role in the small-for-size liver transplantation，but the mechanismwas still unclear. Liver cell regeneration was necessary and inevitable in liver insult,partial liver resection and liver transplantation，especially for small-for-size livertransplantation. In small-for-size liver transplantation, studies showed that ischemiaand reperfusion injury significantly inhibited the proliferation of liver cells, themechanism may be IRI inhibit the IL-6expression which was a critical mediator ininitiation of liver cell proliferation and downstream signal activation, affectingtransition of the liver cells from G0/G1to S phase though down-regulating expression of cyclin D1. Reducing the elimination of ischemia and reperfusioninjury in liver transplantation, promoting restore and regeneration of graft liver cellsis important for the survival of liver transplant graft, reducing postoperativecomplications and amelioration of patient survival and quality of life.The number of functional liver cells was decreased owing to the initiation of livercell proliferation after small-for-size liver transplantation. So, rapidly regeneration ofliver cell was important for induction of postoperative complication. In1993,Przyklenk et al. firstly proposed the concept of remote ischemic preconditioning(remote ischemic reperfusion preconditioning, RIPC), a large number of clinical andanimal studies indicated that the limb remote ischemic preconditioning had a veryimportant role in reducing the heart, lungs and other organs ischemia-reperfusioninjury. Remote ischemic preconditioning (RIPC) could regulate liver blood flow,hemeoxygenase-1, improve the liver microenvironment to reduce liver ischemia andreperfusion injury. The effect of remote ischemic preconditioning (RIPC) on IRI andliver regeneration the small size liver transplantation and its possible mechanism isnot yet clear.Objective: To investigate the effect of liver remote ischemic preconditioning（RIPC）on grafts regeneration in rat small-for-size liver transplantation model, andunderlying mechanism.Methods: Rat models of small-for-size liver transplantation (30%) were established,rats were randomly divided into the pretreatment group and control group. Thetechnique of RIPC involved a limb tourniquet, which we applied around the limb.The procedure involved5min of ischemia followed by5min of reperfusion; thiswas repeated for four cycles. Respectively，the levels of alanine aminotransferase was detected and liver tissue samples were collected to observe morphologicalchanges at2h、6h、12h、24h after transplantation. Hepatocyte replication with Ki-67was confirmed by immunohistochemistry. Proliferation of liver cell DNA and cellcycle were detected with a flow cytometer. The expression of cyclin D1wasrespectively detected by RT-PCR and Western blot.Results: The level of aminotransferase in serum after small-for-size livertransplantation was significantly lower in pretreatment group, but the recovery timeof the control group was earlier than the pretreatment group. Less liver cell necrosisand vacuolar degeneration were appeared in the pretreatment group，the pathologicaldamage of liver in pretreatment group was slighter compared with the control group.Compared with controls, the Ki-67labeling index of the RIPC group wassignificantly higher at24h (57.64%±3.37%vs67.35%±3.44%; P<0.05).CyclinD1,IL-6mRNAexpression levels by RT-PCR in the pretreatment groupwere significantly higher than the control group, TNF-α mRNA expression levelswere significantly lower than the control group, the difference was statisticallysignificant (P <0.05). CyclinD1protein levels are significantly up-regulated in thepretreatment group than the control group.Conclusion: Remote ischemic preconditioning can protect liver grafts againsthistology damage by improving early regeneration after small-for-size livertransplantation. |
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