The Expression Of HIF-1α And The Relationship With SDF-1α In Patients With Chronic Liver Failure

Background: We have found that the expression of SDF-1αwas high in the study of the bone marrow mesenchymal stem cells(MSCs) homing to the injury tissue in liver failure; Moreover, SDF-1αis an important chemokine in mediating the homing of CXCR4+ stem cells to injury tissues. Researches have showed that: HIF-1αis the key upstream transcription factor of SDF-1α. However, little is known about the expression of HIF-1αand its relationship with SDF-1αin chronic liver failure.Objective: To investigate the expression of HIF-1αand its relationship with SDF-1αin chronic liver failure. To study the morphologic changes of microcirculation in chronic liver failure. Methods: Liver tissues were obtained from 21 patients with chronic liver failure and 10 controls receiving liver resection for benign lesions, HIF-1αand SDF-1αwas stained by immunohistochemistry methods. The morphologic changes were observed with light microscope and transmission electron microscope(TEM). Results: (1) Immunohistochemical staining : HIF-1αwas mainly expressed in liver cells and biliary epithelial cells, mainly localized in cell nucleus, partly in cytoplasm. The total positive rate of HIF-1αstaining was 57.1% in chronic liver failure; The normal liver tissues were not seen the positive expression. SDF-1αwas mainly expressed in biliary epithelial cells of interlobular and septal bile ducts, hepatic oval cells also strongly expressed SDF-1αprotein. The expression of SDF-1αwas greatly higher in chronic liver failure than in normal liver tissue(sP<0.05)。There was positive correlation between the expression of HIF-1αand SDF-1αin chronic liver failure (r=0.482, P<0.05). (2)Morphologic changes of microcirculation: The tissues with chronic liver failure were stained by HE, we can observe the ballooning degeneration,extensive necrosis of hepatic cell, congestion and infiltration of inflammatory cell. Through PTAH stained, we can observe a lot of bule microthrombus in hepatic sinusoids and capillary vessel. Through TEM, we can observe the vacuolar degeneration of hepatic cell, mitochondria swelling,cristae decreasing or vanishing. The characteristic manifestation of microcirculation disturbance can be seen: aggregation of red blood cells in hepatic sinusoids, adherence of white blood cells, the number of the fenestrea on sinusoidal endothelial cells were decreased and their sizes were also decreased. The hepatic sinusoids were clear in controls, without stenosis. Conclusion: HIF-1αand SDF-1αwere high expressed in chronic liver failure. There is a positive correlation between them. HIF-1αregulated the expression of SDF-1αin chronic liver failure, which promotes the self-repairment of injury tissue. Microcirculation disturbance is the pathophysiological basis of the expression of HIF-1αin chronic liver failure.