RESTRICTION OF GUT-DERIVED ENDOTOXIN IMPAIRS DNA-SYNTHESIS FOR LIVER-REGENERATION
RESTRICTION OF GUT-DERIVED ENDOTOXIN IMPAIRS DNA-SYNTHESIS FOR LIVER-REGENERATION
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DOI：
10.1152/ajpregu.1985.249.5.r563
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发表时间：
1985-01-01
影响因子：
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通讯作者：
CORNELL, RP
中科院分区：
文献类型：
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作者：
CORNELL, RP
评估了限制肠源性内毒素的可用性对部分肝切除术后肝再生的影响。部分肝切除术是对乙醚麻醉的大鼠进行 67% 的肝切除术。部分肝切除后，通过 [3H] 胸苷掺入肝 DNA 来量化肝再生；通过对高氯酸提取的血浆样品进行定性裂解物测定来测定由于内源性内毒素从肠道吸收到门循环中而引起的内毒素血症，并通过放射免疫测定法来测定血浆中保肝因子胰岛素和胰高血糖素的水平。限制肠源性内毒素的治疗包括长期灌胃新霉素和头孢唑啉进行肠道灭菌，长期灌胃考来烯胺以结合肠道内的内毒素，皮下施用多粘菌素 B 以中和循环内毒素的脂质 A 部分，通过逐渐增加内毒素剂量腹膜内诱导内毒素耐受，以及用隔离器饲养的确定菌群的 Fisher 大鼠进行实验，这些大鼠革兰氏阴性菌缺陷，因此内毒素缺乏。所有限制内源性内毒素的治疗都会损害再生肝脏中的 DNA 合成，尤其是肝切除后 21 小时，此时正常大鼠的复制增加最快。我们假设内毒素限制动物部分肝切除术后 DNA 合成受损是由于观察到 67% 肝切除缺乏正常的全身内毒素血症以及高胰岛素和高胰高血糖素反应。
The influence of restricting gut-derived endotoxin availability on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA; endotoxemia due to absorption of endogenous endotoxin from the gut into the portal circulation was determined by qualitative lysate assay of perchloric acid-extracted plasma samples, and plasma levels of the hepatotrophic factors insulin and glucagon were measured by radioimmunoassay. Treatments to restrict gut-derived endotoxin included chronic gavage with neomycin and cefazolin for gut sterilization, chronic gavage with cholestyramine to bind endotoxin within the gut, subcutaneous administration of polymyxin B to neutralize the lipid A portion of circulating endotoxin, intraperitoneal induction of endotoxin tolerance by progressively higher doses of endotoxin, and experimentation with isolator-reared defined flora Fisher rats that were Gram-negative bacteria deficient and therefore endotoxin deficient. All treatments to restrict endogenous endotoxin impaired DNA synthesis in regenerating livers particularly 21 h posthepatectomy when replication was increasing most rapidly in normal rats. We hypothesize that impairment of DNA synthesis after partial hepatectomy in endotoxin-restricted animals was due to the observed lack of normal systemic endotoxemic as well as hyperinsulinemic and hyperglucagonemic responses to 67% liver resection.