Ballot Orlane, Joseph Vincent, Soliz Jorge
Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, Québec, Quebec, Canada.
Centre de Recherche du CHU de Québec, Pavillon St François d'Assise, Département de Pédiatrie, Faculté de Médecine, Université Laval, Québec, Quebec, Canada
J Appl Physiol (1985). 2015 Jun 1;118(11):1386-95. doi: 10.1152/japplphysiol.00143.2015. Epub 2015 Mar 19.
We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency (fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (-25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (-37% in males, -59% in females) and VT (-38% in males, -47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia.
我们验证了内源性脑源性促红细胞生成素（Epo）是一种呼吸刺激物的假设。成年（3个月）和新生（10天）的雄性和雌性小鼠接受脑池内（枕大池）注射可溶性Epo受体（sEpoR；与EpoR竞争结合Epo；50μg/ml）或赋形剂（PBS中0.1%的牛血清白蛋白）。注射后24小时，我们使用全身体积描记法记录常氧和逐渐暴露于低氧（12%-10%-6% O2；每次10分钟）条件下的分钟通气量（V̇e）、潮气量（VT）、呼吸频率（fR）、氧气消耗量（V̇o2）和二氧化碳产生量（V̇co2）。在成年雄性和雌性小鼠中，sEpoR降低了常氧下的V̇e（-25%），这是由于雄性小鼠的VT降低和雌性小鼠的fR降低所致。此外，sEpoR注射降低了雄性小鼠对12% O2的通气反应，以V̇e/V̇o2或V̇e/V̇co2评估，但雌性小鼠没有。在新生雄性和雌性小鼠中，sEpoR在常氧下降低了V̇e（雄性降低37%，雌性降低59%）和VT（雄性降低38%，雌性降低47%）以及雌性小鼠的fR。在低氧期间，sEpoR降低了两性小鼠的V̇e/V̇o2和V̇e/V̇co2。在极度低氧（6% O2）时，用sEpoR处理的新生小鼠出现呼吸抑制、窒息迹象（喘气），雄性和雌性小鼠的死亡率都很高。我们得出结论，内源性脑源性Epo在成年和新生小鼠的常氧和低氧条件下是一种有效的呼吸刺激物。由于新生雄性和雌性小鼠的性别特异性效应不同，不同年龄小鼠分泌的性类固醇似乎调节了Epo在常氧和对低氧反应中对呼吸调节的作用。
