Lanza-Jacoby S, Rosato E, Braccia G, Tabares A
Department of Surgery, Jefferson Medical College, Philadelphia, PA 19107.
Metabolism. 1990 Nov;39(11):1151-7. doi: 10.1016/0026-0495(90)90087-s.
To investigate why blood ketone bodies are depressed during sepsis, the production and utilization of ketone bodies was studied in fasted control, fasted, Escherichia coli-treated, fed control, and fed E coli-treated rats. Gram-negative sepsis was induced by intravenous (IV) injection of 8 x 10(7) live colonies of E coli per 100 g body weight. Food was removed from the fasted rats after E coli injection. Fed rats were infused intragastrically with a nutritionally adequate diet for 5 days before inducing sepsis. Twenty-four hours after E coli injection, blood ketone bodies were reduced in fasted septic rats and fed septic rats compared with their respective control rats. Ketogenesis and oxidation of labeled palmitate was not altered in hepatocytes from fasted E coli-treated rats. Yet, ketogenesis declined significantly in hepatocytes from fed E coli-treated rats. Oxidation of labeled palmitate was also significantly reduced in hepatocytes from fed E coli-treated rats. Utilization of ketone bodies as measured by the incorporation of [3-14C]beta-hydroxybutyrate into CO2, increased over threefold in the diaphragm, 12% in the heart, and 19% in the kidneys from the fasted E coli-treated rats. In the fed state, incorporation of [3-14C]beta-hydroxybutyrate into CO2 was elevated fivefold in the heart, fourfold in the diaphragm, and over threefold in the kidneys from the septic rats. These results suggest that in the fasted state, plasma ketone bodies remain low during gram-negative sepsis because peripheral tissues use more ketone bodies and because liver ketogenesis is not increased to compensate for the increased utilization. In the fed state, the reduction in blood ketone bodies appears to be attributed to both impaired ketogenic capacity and increased peripheral utilization.
为了研究败血症期间血酮体降低的原因，我们在禁食对照、禁食、大肠杆菌处理、喂食对照和喂食大肠杆菌处理的大鼠中研究了酮体的生成和利用情况。通过每100克体重静脉注射8×10⁷个大肠杆菌活菌落诱导革兰氏阴性败血症。大肠杆菌注射后，从禁食大鼠中移除食物。在诱导败血症前5天，给喂食大鼠胃内输注营养充足的饮食。大肠杆菌注射24小时后，与各自的对照大鼠相比，禁食败血症大鼠和喂食败血症大鼠的血酮体降低。禁食大肠杆菌处理大鼠的肝细胞中标记棕榈酸的生酮作用和氧化未改变。然而，喂食大肠杆菌处理大鼠的肝细胞中生酮作用显著下降。喂食大肠杆菌处理大鼠的肝细胞中标记棕榈酸的氧化也显著降低。通过将[3-¹⁴C]β-羟基丁酸掺入二氧化碳来测量，禁食大肠杆菌处理大鼠的膈肌中酮体的利用率增加了三倍多，心脏中增加了12%，肾脏中增加了19%。在喂食状态下，败血症大鼠心脏中[3-¹⁴C]β-羟基丁酸掺入二氧化碳的量增加了五倍，膈肌中增加了四倍，肾脏中增加了三倍多。这些结果表明，在禁食状态下，革兰氏阴性败血症期间血浆酮体保持较低水平，因为外周组织使用更多的酮体，并且肝脏生酮作用没有增加以补偿增加的利用率。在喂食状态下，血酮体的降低似乎归因于生酮能力受损和外周利用率增加。
