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疟原虫感染小鼠致死的昼夜体温节律及昼夜-近一周(约7天)节律特征

Circadian temperature rhythm and circadian-circaseptan (about 7-day) aspects of murine death from malaria.

作者信息

Sánchez de la Peña S, Halberg F, Schweiger H G, Eaton J, Sheppard J

出版信息

Proc Soc Exp Biol Med. 1984 Feb;175(2):196-204. doi: 10.3181/00379727-175-41788.

DOI:10.3181/00379727-175-41788
PMID:6364151
Abstract

About-7-day (circaseptan) and circadian rhythms were sought and found in host-parasite relations of mice infected with Plasmodium berghei. Five inbred male DBA mice, about 18 weeks of age, were implanted with transsensors for temperature telemetry. Core temperature, monitored every 10 min for 3 days before the intravenous or intraperitoneal inoculation of 10(5) infected erythrocytes and thereafter until death, was analyzed by cosinor. A statistically highly significant circadian rhythm exhibited similarly synchronized acrophases. Core temperatures on the days immediately after malarial infection were mostly within the range of temperatures observed before injection. A mesor-hypothermic stage preceded death by several days. In a second study, 24 male BALB/c and 42 male DBA mice, 12 weeks of age, housed in three rooms on different regimens of light and darkness (alternating at 12-hr intervals), staggered by 8 hr, were inoculated ip with 10(4) infected erythrocytes, one-half at noon, the other half at midnight, within 0.5 hr of blood withdrawal. Thus, one endeavored to cover six circadian host stages (02, 06, 10, 14, 18, and 22 hr after light-on). At 54 and 51% overall mortality (irrespective of inoculation time), a circadian rhythm in susceptibility to malaria was demonstrated in these mice by the single cosinor fit of a 24-hr period (P less than 0.003 and less than 0.020, respectively). The single cosinor fit of a 7-day period further demonstrated a circaseptan rhythm (P = 0.014) in the mortality of both strains following the inoculation of P. berghei. The acrophase (360 degrees = 168 hr) was at -325 degrees from the inoculation time with 95% confidence limits extending from -276 to -378 degrees. Such predictable time relations of P. berghei to its murine host await the exploration of mechanisms underlying the circadian and infradian (7-day) rhythmicities here demonstrated and quantified with their uncertainties. Irrespective of mechanisms, information on such periodicities may also guide attempts to optimize treatment by timing according to the interactions of plasmodial virulence and host resistance that remain to be quantified separately.

摘要

在感染伯氏疟原虫的小鼠宿主-寄生虫关系中寻找并发现了约7天(近一周节律)和昼夜节律。五只约18周龄的近交系雄性DBA小鼠植入了用于温度遥测的传感器。在静脉内或腹腔内接种10⁵个感染红细胞之前3天,每10分钟监测一次核心温度,之后直至死亡,通过余弦分析进行分析。一种具有统计学高度显著性的昼夜节律表现出类似同步的峰值相位。疟疾感染后立即的几天内核心温度大多在注射前观察到的温度范围内。一个中值体温过低阶段在死亡前持续数天。在第二项研究中,将24只12周龄的雄性BALB/c小鼠和42只12周龄的雄性DBA小鼠饲养在三个房间,采用不同的明暗交替方案(以12小时为间隔交替),相差8小时,在采血后0.5小时内,一半在中午腹腔注射10⁴个感染红细胞,另一半在午夜注射。因此,试图涵盖六个昼夜宿主阶段(开灯后02、06、10、14、18和22小时)。在总体死亡率分别为54%和51%(与接种时间无关)时,通过对24小时周期的单余弦拟合,在这些小鼠中证明了对疟疾易感性的昼夜节律(P分别小于0.003和小于0.020)。对7天周期的单余弦拟合进一步证明,接种伯氏疟原虫后,两种品系的死亡率存在近一周节律(P = 0.014)。峰值相位(360° = 168小时)距接种时间为 -325°,95%置信区间从 -276°延伸至 -378°。伯氏疟原虫与其小鼠宿主之间这种可预测的时间关系有待探索这里所证明和量化的昼夜节律和近一周(7天)节律性背后的机制及其不确定性。无论机制如何,关于这种周期性的信息也可能指导根据疟原虫毒力和宿主抵抗力的相互作用来优化治疗时机的尝试,而疟原虫毒力和宿主抵抗力仍有待分别量化。

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