Franke H, Zimmermann T, Dargel R
Virchows Arch B Cell Pathol Incl Mol Pathol. 1985;48(3):277-88. doi: 10.1007/BF02890135.
The effect of a single dose of TAA (100 mg/kg body weight) on intra- and extrahepatic lipoproteins of the very low density (VLDL) type was studied in rats by morphometric and biochemical methods. For a better quantification of VLDL in the periportal (zone 1) and centrilobular (zone 3) hepatocytes of control and TAA-intoxicated livers, colchicine was used as an inhibitor of hepatic lipoprotein secretion. Generally, there exists a great functional heterogeneity between the hepatocytes of zone 1 and 3 in the colchicine-treated controls manifested in a significantly different accumulation rate of VLDL particles. The mean number of VLDL particles per vesicle, the mean secretory vesicle size and the volume density of the electron-lucent secretory vesicles are two times larger in hepatocytes of zone 1 than zone 3. The volume of the VLDL particles amounts to 7.3 X 10(-5) microns3 and 22 X 10(-5) microns3 in the peri- and centrilobular regions. On the other hand, there is no significant lobular-zonal difference in the number of light and dark secretory vesicles. Within 48 h TAA treatment causes a reduction in the number of VLDL particles/100 microns 2 in zone 1 and 3 by 66% and 61%, whereas the number of light secretory vesicles is decreased by 31% and 58%, respectively. The volume density of the latter is significantly diminished only in zone 1. Moreover, the VLDL particle volume is reduced to nearly 50% in each lobular zone examined. The data obtained after TAA treatment from the electron-dense secretory vesicles do not differ significantly from those of the colchicine-treated controls. Acute TAA intoxication lowers the hepatic VLDL-TG output by about 50% in comparison with controls. The steady state of the serum TG concentration after TAA application implies that the clearance of TG from the serum must be diminished to the same extent as the hepatic TG output is found to decrease due to acute liver injury. The results presented here support our view that acute TAA intoxication lowers the hepatic VLDL output by inhibiting the intracellular formation of VLDL. The intrahepatic degradation of the newly synthesized VLDL seems to be unaffected. Despite the fact that the substructure of the hepatocytes in zone 3 is much more changed than in zone 1 after TAA treatment the quantitative data on the VLDL secretory products provide evidence that the process of lipoprotein formation is disturbed to nearly the same extent by TAA both in zone 1 and 3.
采用形态计量学和生化方法，研究了单剂量硫代乙酰胺（TAA，100毫克/千克体重）对大鼠极低密度脂蛋白（VLDL）型肝内和肝外脂蛋白的影响。为了更好地定量对照和TAA中毒肝脏的门周（1区）和小叶中央（3区）肝细胞中的VLDL，秋水仙碱被用作肝脂蛋白分泌的抑制剂。一般来说，在秋水仙碱处理的对照中，1区和3区的肝细胞之间存在很大的功能异质性，表现为VLDL颗粒的积累速率明显不同。1区肝细胞中每个囊泡的VLDL颗粒平均数量、平均分泌囊泡大小和电子透明分泌囊泡的体积密度是3区的两倍。在门周和小叶中央区域，VLDL颗粒的体积分别为7.3×10⁻⁵立方微米和22×10⁻⁵立方微米。另一方面，浅色和深色分泌囊泡的数量在小叶区域之间没有显著差异。在TAA处理的48小时内，1区和3区每100平方微米的VLDL颗粒数量分别减少了66%和61%，而浅色分泌囊泡的数量分别减少了31%和
58%。后者的体积密度仅在1区显著降低。此外，在所检查的每个小叶区域中，VLDL颗粒体积减少到近50%。TAA处理后从电子致密分泌囊泡获得的数据与秋水仙碱处理的对照数据没有显著差异。与对照相比，急性TAA中毒使肝脏VLDL - TG输出降低约50%。TAA应用后血清TG浓度的稳态意味着，由于急性肝损伤导致肝脏TG输出减少的程度，血清中TG的清除率也必须相应降低。此处呈现的结果支持我们的观点：急性TAA中毒通过抑制VLDL的细胞内形成来降低肝脏VLDL输出。新合成的VLDL在肝内的降解似乎未受影响。尽管TAA处理后3区肝细胞的亚结构变化比1区大得多，但关于VLDL分泌产物的定量数据表明，TAA在1区和3区对脂蛋白形成过程的干扰程度几乎相同。
