期刊
BMC ANESTHESIOLOGY
卷 17, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12871-017-0327-1
关键词
Propofol; Hypoxia; Cognitive impairment; HT22
资金
- Nature Science Foundation of Shanghai [14ZR1407500]
Background: Perioperative cerebral ischemia/hypoxia could induce hippocampal injury and has been reported to induce cognitive impairment. In this study, we used cobalt chloride (CoCl2) to build a hypoxia model in mouse hippocampal cell lines. Propofol, a widely used intravenous anesthetic agent, has been demonstrated to have neuroprotective effect. Here, we explored whether and how propofol attenuated CoCl2-induced mouse hippocampal HT22 cell injury. Methods: Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with CoCl2. Cell viability was measured by cell counting kit 8 (CCK8). The effect of propofol on CoCl2-modulated expressions of B-cell lymphoma 2 (Bcl-2), BAX, cleaved caspase 3, phosphatase A2 (PP2A), and the phosphorylation of Ca2+/Calmodulin (CaM)-dependent protein kinase II (pCAMKII alpha), neuron nitric oxide synthase at Ser(1412) (pnNOS-Ser(1412)), neuron nitric oxide synthase at Ser(847) (pnNOS-Ser(847)) were detected by Western blot analysis. Results: Compared with control, CoCl2 treatment could significantly decrease cell viability, which could be reversed by propofol. Further, we found CoCl2 treatment could up-regulate the expression of PP2A, BAX, cleaved caspase three and cause the phosphorylation of nNOS-Ser(1412), but it down-regulated the expression of Bcl-2 and the phosphorylation of CAMKII alpha and nNOS-Ser(847). More importantly, these CoCl2-mediated effects were attentuated by propofol. In addition, we demonstrated that propofol could exert similar effect to that of the PP2A inhibitor (okadaic acid). Further, the PP2A activator (FTY720) and the CAMKII alpha inhibitor (KN93) could reverse the neuroprotective effect of propofol. Conclusion: Our data indicated that propofol could attenuate CoCl2-induced HT22 cells hypoxia injury via PP2A/CAMKIIa/nNOS pathway.
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