Evaluation of hyaluronic acid as a marker of hepatic sinusoidal endothelial cell disorder in chronic liver injury

血清透明质酸(HA)主要由肝窦内皮细胞(SEC)降解。在肝硬变中，肝窦毛细血管形成使SEC中HA的结合和降解减少，从而导致血清HA浓度升高。本研究以硫代乙酰胺(TAA)诱导慢性肝损伤模型大鼠为模型，以生理盐水为对照，探讨血清透明质酸(HA)水平是否为慢性肝损伤SEC紊乱的有用指标。测定TAA组和对照组大鼠血清HA水平和肝组织中14&GT；C-HA放射性水平。在TAA治疗0、4、8、12、16周大鼠的培养SEC中，1)观察SEC.2的窗孔；2)检测抗CD44的免疫荧光强度；3)测定血清HA水平和肝组织中C-HA的结合量。随着慢性肝损伤的进展，SEC中CD-44的数量、孔隙率和表达均呈下降趋势，以肝硬化组最低。此外，肝硬化组与SEC的结合量明显低于对照组，提示慢性肝损伤时血HA浓度升高主要是由于SEC的HA受体减少，从而导致HA与细胞的结合量减少所致。

Most of the serum hyaluronic acid (HA) is degraded by hepatic sinusoidal endothelial cells (SEC). In liver cirrhosis, the bindig and degradation of HA in SEC are considered to be reduced by development of hepatic sinusoidal capillarization, resulting in high serum HA concentration. The aim of this study is to clarify whether serum HA level is an useful marker of SEC disorder in chronic liver injury.Chronic liver injury model rats were induced by thioacetamide (TAA) administration and control rats by physiologic saline. Serum HA levels and ^<14>C-HA radioactivity of liver tissues in TAA and control rats were measured. In cultured SEC obtained from 0,4,8,12 and 16-week TAA treated rats, 1) the observation of fenestrae in SEC.2) the immunofluorescent intensity of anti-CD44, and 3) the amount of ^<14>C-HA binding were determined.Serum HA levels ad ^<14>C-HA radioactivity of liver tissues increased with progression of chronic liver injury, and were the highest in liver cirrhosis. The number, porosity and expression of CD-44 in SEC decreased with progression of chronic liver injury and were the lowest in liver cirrhosis. Moreover, the amount of ^<14>C-HA binding to SEC significantly decreased in liver cirrhosis compared with the controls.These results indicate that the elevation of the blood HA concentration in chronic liver injury mainly occurs from a reduction in HA receptors of SEC and a consequent reduction in the amount of HA binding to the cells.