Endocrine and neurobehavioral abnormalities induced by propofol administered to neonatal rats.
Endocrine and neurobehavioral abnormalities induced by propofol administered to neonatal rats.
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DOI：
10.1097/aln.0000000000000366
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发表时间：
2014-11
期刊：
影响因子：
8.8
通讯作者：
Martynyuk AE
中科院分区：
文献类型：
--
作者：
Tan S;Xu C;Zhu W;Willis J;Seubert CN;Gravenstein N;Sumners C;Martynyuk AE
我们研究了新生儿异丙酚麻醉是否影响内分泌和神经系统的发育。Sprague-Dawley大鼠在出生后第4、5或6天（P）使用腹腔内丙泊酚麻醉5 h。接受生理盐水或胰岛素治疗的幼仔（阴性对照组未接受）也与母体分离5 h。分别于麻醉后即刻和成年后进行声惊吓试验（≥P80）的前脉冲抑制（PPI）后测定血清皮质酮水平，然后测定海马神经元活性。异丙酚使皮质酮水平急剧升高至146.6 ± 23.5 ng/ml（n=6），而生理盐水组和内毒素组的皮质酮水平分别为16.4 ± 3.5 ng/ml（n=6）和18.4 ± 3.2 ng/ml（n=6）。在成年期，丙泊酚组表现出对应激的内分泌反应加剧，表现为皮质酮水平升高（1171.58 ± 149.17 ng/ml（n=15）vs 370.02 ± 36.01 ng/ml（n=10））。异丙酚组可增加雄性和雌性大鼠海马CA 1区神经元的抑制性突触后电流频率，但仅在雄性大鼠中检测到惊吓的PPI降低。在丙泊酚给药前给予幼仔Na+-K+-2Cl−协同转运蛋白抑制剂布美他尼，可缓解长期内分泌和PPI异常。外源性皮质酮，给药到幼稚的幼崽，诱导突触和内分泌，但不是PPI的影响，类似于丙泊酚。异丙酚引起的皮质酮水平的急性增加和γ-氨基丁酸A型受体介导的兴奋在麻醉时可能发挥机械作用的发展加剧的内分泌应激反应和神经行为异常。
We studied whether neonatal propofol anesthesia affects development of the endocrine and neural systems. Sprague-Dawley rats were anesthetized using intraperitoneal propofol for 5 h on postnatal days (P) 4, 5, or 6. Pups that received either saline or intralipid, but not those in the negative control groups, were also maternally separated for 5 h. Serum levels of corticosterone were measured immediately after anesthesia and in adulthood after prepulse inhibition (PPI) of acoustic startle testing (≥P80), followed by measurement of hippocampal neuronal activity. Propofol acutely increased corticosterone levels to 146.6 ± 23.5 ng/ml (n=6) vs 16.4 ± 3.5 ng/ml (n=6) and 18.4 ± 3.2 ng/ml (n=6) in saline- and intralipd-treated pups, respectively. In adulthood, the propofol group exhibited exacerbated endocrine responses to stress in a form of increased corticosterone levels (1171.58 ± 149.17 ng/ml (n=15) vs 370.02 ± 36.01 ng/ml (n=10) in the saline group). The propofol group had increased the frequency of miniature inhibitory postsynaptic currents in CA1 neurons of male and female rats, but reduced PPI of startle was detected only in males. The Na+–K+–2Cl− co-transporter inhibitor bumetanide, administered to pups prior to propofol, alleviated long-term endocrine and PPI abnormalities. Exogenous corticosterone, administered to naïve pups, induced synaptic and endocrine, but not PPI effects, similar to those of propofol. Propofol-caused acute increases in corticosterone levels and gamma-aminobutyric acid type A receptor-mediated excitation at the time of anesthesia may play mechanistic roles in development of exacerbated endocrine responses to stress and neurobehavioral abnormalities.