Turnbull Isaiah R, Wlzorek Joseph J, Osborne Dale, Hotchkiss Richard S, Coopersmith Craig M, Buchman Timothy G
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110-1093, USA.
Shock. 2003 Apr;19(4):310-3. doi: 10.1097/00024382-200304000-00003.
The incidence and mortality of sepsis increase with age, consequently, 80% of the clinical mortality from sepsis occurs in patients over age 65. Despite this aged clinical population, most research models of sepsis use 6- to 16-week-old mice as patient surrogates. This age range of mice corresponds to human ages 10 to 17 years. To assess the influence of age on rodent CLP and on antibiotic therapy, we studied young (4 month), mature (12 month), and aged (24 month) mice. Male C57BL/6 mice (n = 27-30 in each age group) were subjected to cecal ligation and puncture (CLP), two punctures with a 25-gauge needle. Mice were observed untreated for 10 days. Young mice had 20% mortality, mature mice had 70% mortality (P = 0.0013 vs. young), and aged mice had 75% mortality (P = 0.0001 vs. young). To assess the effects of age on antibiotic therapy, mice were subjected to CLP as above (n = 38-40 in each age group). Mice were then randomized to treatment with intraperitoneal injections of ceftriaxone and metronidazole or normal saline. Therapy was initiated 12 h after CLP, and injections were repeated every 12 h for 7 days. Young mice saw a 56% decrease in mortality from CLP with antibiotic therapy (P = 0.001), and mature mice had a 30% decrease in mortality (P = 0.06). Aged mice saw no benefit from antibiotic therapy. We also compared plasma cytokine levels between young and aged mice after CLP. When compared with young mice, aged mice had higher levels of IL-6 and TNF-alpha 24 h after CLP. However, high IL-6 was predictive of mortality at any age. Mice appear to have age-dependent responses to intra-abdominal sepsis and to appropriate therapy.
脓毒症的发病率和死亡率随年龄增长而增加，因此，80%的脓毒症临床死亡率发生在65岁以上的患者中。尽管存在这样一个老年临床群体，但大多数脓毒症研究模型使用6至16周龄的小鼠作为患者替代物。这个小鼠年龄范围相当于人类10至17岁的年龄。为了评估年龄对啮齿动物盲肠结扎穿孔术（CLP）及抗生素治疗的影响，我们研究了年轻（4个月）、成熟（12个月）和老年（24个月）小鼠。雄性C57BL/6小鼠（每个年龄组n = 27 - 30）接受盲肠结扎穿孔术（CLP），用25号针头穿刺两次。观察小鼠10天不进行治疗。年轻小鼠死亡率为20%，成熟小鼠死亡率为70%（与年轻小鼠相比，P = 0.0013），老年小鼠死亡率为75%（与年轻小鼠相比，P = 0.0001）。为了评估年龄对抗生素治疗的影响，小鼠按上述方法接受CLP（每个年龄组n = 38 - 40）。然后将小鼠随机分为接受腹腔注射头孢曲松和甲硝唑或生理盐水治疗。在CLP后12小时开始治疗，每12小时重复注射一次，持续7天。接受抗生素治疗的年轻小鼠CLP死亡率降低了56%（P = 0.001），成熟小鼠死亡率降低了30%（P = 0.06）。老年小鼠未从抗生素治疗中获益。我们还比较了CLP后年轻和老年小鼠的血浆细胞因子水平。与年轻小鼠相比，老年小鼠在CLP后24小时IL - 6和TNF -α水平更高。然而，高IL - 6可预测任何年龄的死亡率。小鼠似乎对腹腔内脓毒症及适当治疗有年龄依赖性反应。
