期刊
NEUROLOGICAL RESEARCH
卷 41, 期 10, 页码 923-929出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/01616412.2019.1642564
关键词
Ulinastatin; postoperative neurocognitive disease; isoflurane; beta-amyloid peptide; inflammatory cytokine
资金
- Guangzhou Science, Technology and Innovation Commission [201704020222]
- National Natural Science Foundation of Guangdong, China [2018A0303130195]
- National Science Foundation of China [81201022]
- Techpool Research Fund [UF201306]
Objective: Postoperative neurocognitive disease (PNCD) in the aged is a major clinical problem with unclear mechanisms. This study was designed to explore the mechanisms for ulinastatin (UTI) to attenuate isoflurane-induced cognitive decline in Fischer-344 rats. Methods: The rats were divided into four groups: Control (0.9% saline only), Isoflurane (exposure to 1.2% isoflurane), Isoflurane-plus-UTI (exposure to 1.2% isoflurane followed by 100,000 U/kg UTI injection i.v.) and UTI-plus-isoflurane (i.v. of 100,000 U/kg UTI followed by 1.2% isoflurane exposure). After respective tests, the concentrations of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the brain were determined by ELISA the expression of beta-amyloid peptide (A beta) and cleaved caspase-3 were measured by Western blot. Ratio of apoptotic cells after Barnes maze challenge was assessed by TUNEL assay. Results: In both Barnes Maze training and challenge, results indicated isoflurane-impaired learning capacity, while pre-and post-treatment with UTI could attenuate this phenomenon. The ratio of apoptotic cells and the expression of cleaved caspase-3 were increased after isoflurane exposure, indicating that isoflurane could induce neuronal apoptosis, while both pre- and post-treatment with UTI could diminish these effects. Moreover, UTI inhibited the expression of TNF-alpha, IL-1 beta and A beta induced by isoflurane in rat brain harvested at 16 h after isoflurane exposure. Conclusion: These results suggest that UTI inhibits neuronal apoptosis in rat brain by attenuating increased expression of A beta(42) and inflammatory cytokines, which may contribute to its alleviation of isoflurane-induced cognitive dysfunction in rats. Moreover, UTI pre-treatment before isoflurane exposure showed more effective than post-treatment.
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