Full
Outline
To explore whether dexmedetomidine (Dex) improves sevoflurane (Sev)-induced cognitive impairment in neonatal rats by regulating mammalian rapamycin target protein (mTOR)/nuclear factor-κB (NF-κB) signaling pathway.
Fifty neonatal SD rats (aged 6 d, weighing 9.5~11.5 g) were randomly divided into 5 groups: sham operation (Sham) group, model (Model) group, low-dose Dex (Dex-L) group, high-dose Dex (Dex-H) group, and phorbol 12-myristate 13-acetate (PMA) group (an activator of mTOR/NF-κB signaling pathway), with 10 animals in each group. The rats in the Sham group were placed in a sealed chamber containing fresh air, while those rats from the other 4 groups were exposed to 2% Sev+21% O₂ for modeling. In 2 h before chamber placement, the Dex-L and Dex-H groups received an intraperitoneal injection of 10 and 30 μg/kg Dex, respectively, and the PMA group received an intraperitoneal injection of 30 μg/kg Dex and 5 mg/kg PMA. The rats in the Sham and Model groups were given an intraperitoneal injection of equivalent volume of normal saline. Cognitive function and learning and memory abilities were evaluated with novel object recognition test and step-down inhibitory avoidance test. Laser speckle contrast imaging (LSCI) was used to observe cerebral blood flow; Nissl staining and transmission electron microscopy were employed to observe the ultrastructure of hippocampal neurons and synapses. TUNEL staining was perform to detect the cell apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to measure the expression levels of mTOR, NF-κB, postsynaptic density protein 95 (PSD95), synaptophysin (SYP), synapsin (SYP), microtubule-associated protein-2 (Map-2), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax) in the hippocampal tissue. Western blotting was conducted to detect the protein levels of mTOR, p-mTOR, NF-κB, p-NF-κB, Bcl-2, and Bax in the hippocampal tissue.
Compared with the Sham group, the Model group exhibited significantly lower discrimination index and shorter platform jumping latency, increased number of errors (P<0.05), reduced cerebral blood perfusion, decreased number of hippocampal neurons, damaged synaptic structure, raised apoptotic rate, enhanced expression of p-mTOR, p-NF-κB and Bax at mRNA and protein levels (P<0.05), while down-regulated mRNA levels of SYN, Map-2, SYP and PSD95 (P<0.05), and reduced mRNA and protein expression of Bcl-2 (P<0.05). After the intervention of Dex, all the above indexes were significantly improved (P<0.05), and the effects of high dose were better. PMA partially reversed the protective effects of Dex-H, reactivated the signal of mTOR/NF-κB, and aggravated the neuronal damage (P<0.05).
Dex may alleviate cognitive dysfunction in neonatal rats by inhibiting the mTOR/NF-κB signaling pathway and suppressing Sev-induced hippocampal neuronal apoptosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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