Nakano M, Lieber C S
Am J Pathol. 1982 Feb;106(2):145-55.
Perivenular fibrosis was studied in baboons pair-fed with alcohol containing or isocaloric control diets for up to 8.5 years, and biopsies were performed on the animals one to two times a year. The number and types of mesenchymal cells surrounding the terminal hepatic venules were examined at various stages of thickening of the rim of the terminal hepatic venules by light and electron microscopy. The number of mesenchymal cells increased with progression of fibrosis and showed good correlation with the thickness of the rim (r = 0.7435, P less than 0.001, n = 56). myofibroblasts were the most common mesenchymal cells. They were present around the terminal hepatic venules in the control animals and proliferated after alcohol. This was associated with increased deposition of collagen fibers around the terminal hepatic venules. This fibrotic process extended into the perisinusoidal space of the centrolobular areas, sometimes connecting with pericellular fibrosis and/or fat granuloma, which developed in the lobule. Thus, in baboons fed alcohol, perivenular fibrosis is associated with myofibroblast proliferation followed by collagen deposition. Myofibroblast proliferation appears to represent the earliest detectable precursor lesion leading to hepatic fibrosis in alcoholic liver injury.
对成对喂养含酒精或等热量对照饮食长达8.5年的狒狒进行终末肝静脉周围纤维化研究，每年对动物进行一到两次活检。通过光镜和电镜在终末肝静脉边缘增厚的不同阶段检查终末肝静脉周围间充质细胞的数量和类型。间充质细胞数量随纤维化进展而增加，且与边缘厚度呈良好相关性（r = 0.7435，P < 0.001，n = 56）。肌成纤维细胞是最常见的间充质细胞。它们存在于对照动物的终末肝静脉周围，在摄入酒精后增殖。这与终末肝静脉周围胶原纤维沉积增加有关。这种纤维化过程延伸至中央小叶区域的窦周间隙，有时与小叶内发生的细胞周围纤维化和/或脂肪肉芽肿相连。因此，在喂食酒精的狒狒中，终末肝静脉周围纤维化与肌成纤维细胞增殖及随后的胶原沉积有关。肌成纤维细胞增殖似乎代表了酒精性肝损伤中导致肝纤维化最早可检测到的前驱病变。
