Pereira F E, Motta L, Cardoso A A
Laboratory of Experimental Pathology, Santa Casa de Vitória School of Medicine, Brazil.
Arq Gastroenterol. 1997 Jul-Sep;34(3):157-62.
Kupffer cells have been implicated in the pathogenesis of liver injury, but there is controversy about the effects of activation of these cells on the hepatotoxicity of chemicals and endotoxin. It has been shown that injection of Corynebacterium parvum in rats induces macrophage activation that protects against toxic effects of carbon tetrachloride and acetaminophen, five days after injection, and this protection is due to inhibition of microsomal oxidizing enzymes and increased production of glutathion. To verify if the protective effect occurs soon after Kupffer cell activation, with different activators, male albino rats were treated with intravenous injection of BCG (0.5 ml with 7.5.10(8) bacilli), Corynebacterium parvum (30 mg/kg) or zymosan (7.5.10(6) yeast cells). Fourty-eight hours after the injection of one of the macrophage activators, the animals and rats treated with intravenous injection of saline (controls) received carbon tetrachloride by subcutaneous route (1 ml/kg of CCl4, 3:1 in soybean oil). Fourty-eight hours after the animals were killed after ether anesthesia and fragments of the liver were fixed, paraffin embedded and the sections stained with hematoxylin and eosin. A Weibel grid with 168 points was used to estimate the percent volume of necrosis and severe hydropic degeneration. The results showed that the volume density of necrosis and severe hydropic degeneration were significatively lesser in rats treated with the three Kupffer cells activators. The protection was greater with BCG and Corynebacterium parvum than with zymosan. These results confirm that activation of Kupffer cell with three different activators can induce protection against liver cell injury produced by carbon tetrachloride in rats soon as 48 h after injection of activators.
库普弗细胞与肝损伤的发病机制有关，但这些细胞的激活对化学物质和内毒素肝毒性的影响存在争议。研究表明，给大鼠注射微小棒状杆菌可诱导巨噬细胞活化，在注射五天后可预防四氯化碳和对乙酰氨基酚的毒性作用，这种保护作用是由于微粒体氧化酶的抑制和谷胱甘肽产量的增加。为了验证库普弗细胞激活后不久是否会产生保护作用，使用不同的激活剂，对雄性白化大鼠进行静脉注射卡介苗（0.5毫升含7.5×10⁸ 杆菌）、微小棒状杆菌（30毫克/千克）或酵母聚糖（7.5×10⁶ 酵母细胞）处理。在注射其中一种巨噬细胞激活剂48小时后，给这些动物和静脉注射生理盐水的大鼠（对照组）经皮下途径注射四氯化碳（1毫升/千克 CCl₄，在大豆油中为3:1）。在乙醚麻醉后处死动物，48小时后将肝组织碎片固定、石蜡包埋，切片用苏木精和伊红染色。使用一个有168个点的韦贝尔网格来估计坏死和严重水样变性的体积百分比。结果表明，用三种库普弗细胞激活剂处理的大鼠中，坏死和严重水样变性的体积密度显著较小。卡介苗和微小棒状杆菌的保护作用比酵母聚糖更大。这些结果证实，用三种不同的激活剂激活库普弗细胞可在注射激活剂后48小时内诱导对大鼠四氯化碳所致肝细胞损伤的保护作用。
