Deaciuc I V, Spitzer J A
Am J Physiol. 1986 Nov;251(5 Pt 2):R984-95. doi: 10.1152/ajpregu.1986.251.5.R984.
Rats were treated with Escherichia coli endotoxin (ET) either acutely or chronically or rendered septic by cecal ligation and puncture. At 6 h after ET injection, at various intervals of continuous ET infusion, and at 17-18 h after the onset of peritonitis, animals were killed and hepatocytes were isolated. Cytosolic [Ca2+] ([Ca2+]c) was measured by quin 2 during the resting state and after stimulation with epinephrine and vasopressin. Basal and epinephrine-, vasopressin- and glucagon-stimulated glycogen phosphorylase activity were also determined. In hepatocytes from acutely ET-treated rats, resting levels of [Ca2+]c were decreased 46% from 245.8 +/- 11.0 to 131.0 +/- 8.5 nM (n = 4-6, P less than 0.05). In septic rats a 39.5% decrease was noted [i.e., from 154.0 +/- 17.7 (n = 4, sham) to 93.3 +/- 91 nM (n = 5, septic, P less than 0.05)]. These decreased [Ca2+]c levels were associated with changes of glycogen phosphorylase activity in a manner suggesting a cause and effect relationship; e.g., acute ET treatment resulted in greater than 80% depression of phosphorylase a activity, whereas sepsis induced a 58% decrease in the activity of this enzyme. In ET-infused rats the resting level of [Ca2+]c and its response to hormonal stimulation were not different from hepatocytes of saline-infused rats, although glycogen phosphorylase activity was less responsive to these hormones. The effect on the enzyme's response to Ca2+-mobilizing hormones was more marked than to glucagon. This is consistent with the concept that information flow in the Ca2+-messenger system is a site of metabolic lesions produced by endotoxicosis and sepsis.
将大鼠进行急性或慢性大肠杆菌内毒素（ET）处理，或通过盲肠结扎和穿刺使其发生败血症。在ET注射后6小时、持续ET输注的不同时间间隔以及腹膜炎发作后17 - 18小时，处死动物并分离肝细胞。在静息状态以及用肾上腺素和血管加压素刺激后，用喹啉2测量细胞溶质[Ca2+]（[Ca2+]c）。还测定了基础以及肾上腺素、血管加压素和胰高血糖素刺激后的糖原磷酸化酶活性。在急性ET处理的大鼠肝细胞中，[Ca2+]c的静息水平从245.8±11.0 nM降至131.0±8.5 nM，降低了46%（n = 4 - 6，P < 0.05）。在败血症大鼠中，观察到降低了39.5%[即从154.0±17.7（n = 4，假手术组）降至93.3±91 nM（n = 5，败血症组，P < 0.05）]。这些降低的[Ca2+]c水平与糖原磷酸化酶活性的变化相关，其方式表明存在因果关系；例如，急性ET处理导致磷酸化酶a活性降低超过80%，而败血症导致该酶活性降低58%。在ET输注的大鼠中，[Ca2+]c的静息水平及其对激素刺激的反应与生理盐水输注大鼠的肝细胞没有差异，尽管糖原磷酸化酶活性对这些激素的反应较弱。对该酶对钙动员激素反应的影响比对胰高血糖素的影响更明显。这与内毒素血症和败血症产生的代谢损伤部位是Ca2+信使系统中的信息流这一概念一致。
