Study On The Mechanism Of Liver Microcirculation Disturbance In Patients With Chronic Hepatitis B

Objective: To explore the mechanism of liver microcirculation disturbance inpatients with chronic hepatitis B(CHB) from point of view of pathohistology byobserving the changes of stereology indexes of sinus hepaticus and ultrastructure of liver,and detecting apoptosis rate of liver cells and the expression of hypoxia-inducible factor1α(HIF-1α) in liver of patients with CHB.Methods: Liver biopsy tissue were collected from81patients with CHB whomwere final diagnosed by serology methods and5normal liver tissues.The liver tissueswere divided to2parts. One of the parts was put into10%formalin(at least12h),thenimbedded in paraffin, continuously cut sheet for4μm, dyed by HE, observed underlight microscop and to analyze stereology indexes of sinus hepaticus. The apoptosis rateof liver cells was detected by TUNEL method and expression of HIF-1αwas detected byimmunohistochemistry stain. The other part was put into2.5%glutaral, then put intoosmic acid, washed by0.1M phosphate buffer, gradually alcoholic dehydrated,imbedded in EP812resin, cut sheets by ultramicrotome, then dyed by uranyl acetate andLead Citrate, observed by transmission electron microscope(TEM).Results: Accompany with the pathological changes of liver in patients with CHB,the stenosis, blockage, dilation and sinusoidal capillarization turned gradually obviouslyand the number of sinus hepaticus turned smaller gradually, but the total area, totalperimeter and average diameter turned bigger gradually. The rate of liver cells apoptosisincreased remarkably. Ultrastructure of liver showed that Disse space was blocked bylympholeukocyte, rhodocyte, glycogen granule and so on. Vacuoles, karyopyknosis,pyrenolysis, chromatic agglutination appear in some liver cells and double-deck ofcaryotheca disappeared. A few chondriosome swell to globular. Some membranolysisand material of intracytoplasm flowed outward. Some liver cells disorganized and cellorgans of intracytoplasm disappeared. A lot of sinusoidal endothelial cells(SECs)intruded into Disse space. The cell nucleus of SECs turned bigger and turned to orbicular-ovate or anomal-shape. The appearance of SECs showed reductus. Decreasedsizes and reduced numbers of sinusoidal endothelial cells’ penestrate and basal laminacan be found on SECs.The electro macula densa appeared on junction of two SECs. Thevolume of hepatic stellate cells(HSCs) turned smaller and lipid droplet turned less ofintracytoplasm. Collagenous fibril beside the HSCs turned notablely more and the HSCstransformed gradually to myofibroblasts. The expression of HIF-1α was detected onliver cells, SECs and HSCs. There is a positive correlation between the expression ofHIF-1α and pathological changes of liver.Conclusion: The pathohistology mechanism of liver microcirculation disturbance inpatients with CHB is maybe concerned with factors as follows:①Reduction of sinushepaticus density;②sinusoidal capillarization;③formation of WP bodies insinusoidal endothelial cells;④Apoptosis and necrosis of liver cells increased;⑤Activationof hepatic stellate cells;⑥Abnormal expression of HIF-1αin liver tissues of patientswith CHB.