Rose S, Thompson K D, Sayeed M M
Department of Physiology, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois 60153.
Am J Physiol. 1992 Sep;263(3 Pt 2):R553-8. doi: 10.1152/ajpregu.1992.263.3.R553.
Intra-abdominal sepsis was induced in rats by implanting into their abdominal cavities fecal-agar pellets impregnated with Escherichia coli and Bacteroides fragilis. Sham-operated rats received sterile pellets. A group of sterile- and septic-implanted rats was treated intraperitoneally with diltiazem (1.2 mg/kg) 8 h after implantations. Septic- and sterile-implanted rat hepatocytes were loaded with 1) the fluorescent dye indo-1 to quantify hepatocyte basal and vasopressin (100 nM)-elevated cytosolic Ca2+ concentration and 2) 45Ca to quantify Ca2+ flux and cellular content of exchangeable Ca2+. Lipid peroxidation was determined by measuring conjugated dienes (CD) and thiobarbiturate-reactive substances (TBA-RS) in liver homogenates. In septic-implanted rats, the basal cytosolic [Ca2+], cellular exchangeable Ca2+, Ca2+ flux, CD, and TBA-RS were significantly higher than in sterile-implanted rats. Although vasopressin caused a significant elevation in cytosolic [Ca2+] in septic rat hepatocytes, the magnitude of this elevation was significantly smaller than that found in the sterile group. Diltiazem treatment of septic rats significantly decreased basal cytosolic [Ca2+], cellular exchangeable Ca2+ content, Ca2+ flux, CD, and TBA-RS. Also, vasopressin-induced increase in hepatocyte cytosolic [Ca2+] in diltiazem-treated septic rats was significantly greater than that observed in untreated septic rats. Both Ca2+ and membrane lipid alterations were attenuated with diltiazem treatment of septic rats. These results suggest that prevention or attenuation of Ca2+ channel-mediated Ca2+ influx restores both Ca2+ homeostasis and membrane lipid alteration.
通过向大鼠腹腔内植入含有大肠杆菌和脆弱拟杆菌的粪便 - 琼脂小球来诱导大鼠发生腹腔内脓毒症。假手术大鼠接受无菌小球。一组植入无菌小球和脓毒症小球的大鼠在植入后8小时腹腔内注射地尔硫䓬（1.2毫克/千克）。将植入脓毒症小球和无菌小球的大鼠肝细胞分别负载：1）荧光染料indo - 1以定量肝细胞基础和血管加压素（100纳摩尔）升高后的胞质Ca2 +浓度；2）45Ca以定量Ca2 +通量和可交换Ca2 +的细胞含量。通过测量肝匀浆中的共轭二烯（CD）和硫代巴比妥酸反应性物质（TBA - RS）来测定脂质过氧化。在植入脓毒症小球的大鼠中，基础胞质[Ca2 +]、细胞可交换Ca2 +、Ca2 +通量、CD和TBA - RS显著高于植入无菌小球的大鼠。尽管血管加压素使脓毒症大鼠肝细胞中的胞质[Ca2 +]显著升高，但这种升高的幅度明显小于无菌组。地尔硫䓬治疗脓毒症大鼠可显著降低基础胞质[Ca2 +]、细胞可交换Ca2 +含量、Ca2 +通量、CD和TBA - RS。此外，在接受地尔硫䓬治疗的脓毒症大鼠中，血管加压素诱导的肝细胞胞质[Ca2 +]增加显著大于未治疗的脓毒症大鼠。地尔硫䓬治疗脓毒症大鼠可减轻Ca2 +和膜脂质的改变。这些结果表明，预防或减弱Ca2 +通道介导的Ca2 +内流可恢复Ca2 +稳态和膜脂质改变。
