Durham S K, Brouwer A, Barelds R J, Horan M A, Knook D L
TNO Institute for Experimental Gerontology, Rijswijk, The Netherlands.
J Pathol. 1990 Dec;162(4):341-9. doi: 10.1002/path.1711620412.
Recent studies have demonstrated that aged rats are more susceptible to the lethal effects of endotoxin (ET) than young rats. The early (15 min to 7 h) hepatic ultrastructural and biochemical changes induced by ET in young (6 months) and aged (24 months) rats were evaluated to elucidate cell populations and/or the mechanisms that may be responsible for the previously observed differential effects. Aged rats given ET had significantly increased numbers of neutrophils in hepatic sinusoids at 30 min and thereafter as compared with ET-treated young rats. Morphologic evidence of coagulation within hepatic sinusoids, including aggregates of fibrin enmeshed among polymorphonuclear leukocytes and platelet aggregates, was frequently observed in ET-treated aged rats but not in ET-treated young rats. In contrast, Kupffer cells of ET-treated young rats frequently contained phagocytized neutrophils and platelets, whereas this phenomenon was rarely observed in Kupffer cells of ET-treated aged rats. Hepatocellular morphologic injury was more pronounced and occurred at earlier time periods in ET-treated aged rats, and was accompanied by significant increase in hepatic transaminases. ET-treated aged rats had an earlier onset and greater severity of endothelial cell injury than did ET-treated young rats. The results of this study indicate a greater aggregation of blood elements in the hepatic sinusoids of aged rats following the intravenous administration of ET, which suggests that a greater diminution in microcirculation was induced in aged rats by ET. Additionally, the increased phagocytosis of inflammatory cells by Kupffer cells of young rats may be a mechanism which affords protection against endotoxin-induced lethality.
最近的研究表明，老年大鼠比年轻大鼠更容易受到内毒素（ET）致死效应的影响。评估了ET在年轻（6个月）和老年（24个月）大鼠中诱导的早期（15分钟至7小时）肝脏超微结构和生化变化，以阐明可能导致先前观察到的差异效应的细胞群体和/或机制。与接受ET治疗的年轻大鼠相比，接受ET的老年大鼠在30分钟及之后肝血窦中的中性粒细胞数量显著增加。在接受ET治疗的老年大鼠中经常观察到肝血窦内凝血的形态学证据，包括纤维蛋白聚集体包裹在多形核白细胞和血小板聚集体中，而在接受ET治疗的年轻大鼠中未观察到。相反，接受ET治疗的年轻大鼠的枯否细胞经常含有吞噬的中性粒细胞和血小板，而在接受ET治疗的老年大鼠的枯否细胞中很少观察到这种现象。在接受ET治疗的老年大鼠中，肝细胞形态学损伤更明显且发生在更早的时间段，并伴有肝转氨酶显著升高。与接受ET治疗的年轻大鼠相比，接受ET治疗的老年大鼠内皮细胞损伤的发作更早且更严重。本研究结果表明，静脉注射ET后，老年大鼠肝血窦中血液成分的聚集更多，这表明ET在老年大鼠中诱导了更大程度的微循环减少。此外，年轻大鼠枯否细胞对炎性细胞吞噬作用的增加可能是一种对内毒素诱导的致死性提供保护的机制。
