Ramm G A, Crawford D H, Powell L W, Walker N I, Fletcher L M, Halliday J W
The University of Queensland Department of Medicine, Australia.
J Hepatol. 1997 Mar;26(3):584-92. doi: 10.1016/s0168-8278(97)80424-2.
BACKGROUND/AIMS: Activated hepatic stellate cells produce increased levels of collagen in animal models of chronic iron overload; however, their role in human genetic haemochromatosis is unknown. This study examined the relationship between hepatic iron concentration and hepatic stellate cell activation in genetic haemochromatosis.
Liver biopsies from 75 patients (55 with haemochromatosis, 14 haemochromatosis patients both pre- and post-phlebotomy and six non iron-loaded disease control subjects) were stained for iron using Perls' Prussian Blue. Thirty biopsies in which there was no evidence of either steatosis or inflammation were subjected to immunohistochemistry for alpha-smooth muscle actin and desmin and counterstained for iron. Forty-five biopsies demonstrated either steatosis or inflammation, in addition to excess iron.
Stellate cells were identified by light microscopy as perisinusoidal cells containing numerous intracellular fat droplets. alpha-Smooth muscle actin was detected in biopsies with an hepatic iron concentration >60 micromol/g dry weight. Increasing hepatic iron concentration and hepatic iron index correlated with an increase in alpha-smooth muscle actin expression (r=0.81 and 0.72, respectively). Phlebotomy resulted in a significant decrease in alpha-smooth muscle actin expression. In early disease prior to histological evidence of collagen deposition, whilst activated stellate cells were located in Zone 1, greater numbers were found in Zones 2 and 3 distal to the region of heaviest iron overload.
This study has demonstrated for the first time in humans a correlation between hepatic iron concentration and stellate cell activation in haemochromatosis, which is reversed by iron removal. Humoral factors from either iron-loaded hepatocytes or activated Kupffer cells may be responsible for early stellate cell activation in areas of the liver remote from heavy iron loading.
背景/目的：在慢性铁过载动物模型中，活化的肝星状细胞产生的胶原蛋白水平升高；然而，它们在人类遗传性血色素沉着症中的作用尚不清楚。本研究探讨了遗传性血色素沉着症中肝脏铁浓度与肝星状细胞活化之间的关系。
对75例患者（55例血色素沉着症患者、14例放血治疗前后的血色素沉着症患者和6例非铁过载疾病对照受试者）的肝活检组织进行普鲁士蓝染色以检测铁。对30例无脂肪变性或炎症证据的活检组织进行α-平滑肌肌动蛋白和结蛋白的免疫组织化学染色，并对铁进行复染。45例活检组织除铁过量外还表现出脂肪变性或炎症。
通过光学显微镜将星状细胞鉴定为含有大量细胞内脂肪滴的窦周细胞。在肝铁浓度>60 μmol/g干重的活检组织中检测到α-平滑肌肌动蛋白。肝脏铁浓度和肝脏铁指数的增加与α-平滑肌肌动蛋白表达的增加相关（分别为r=0.81和0.72）。放血治疗导致α-平滑肌肌动蛋白表达显著降低。在胶原沉积的组织学证据出现之前的早期疾病中，虽然活化的星状细胞位于1区，但在铁过载最严重区域远端的2区和3区发现了更多的活化星状细胞。
本研究首次在人类中证明了血色素沉着症中肝脏铁浓度与星状细胞活化之间的相关性，这种相关性可通过去除铁而逆转。来自铁过载肝细胞或活化的库普弗细胞的体液因子可能是肝脏远离严重铁过载区域早期星状细胞活化的原因。
