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The Mammalian Target Of Rapamycin (Mtor) Inhibitor Rapamycin Improves Postoperative Cognitive Dysfunction (Pocd)

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2016)

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摘要
Background: Several lines of evidence have indicated that rapamycinacts as an inhibitor of the mammalian target of rapamycin (mTOR), and this inhibition has therapeutic benefits as a treatment for postoperative cognitive dysfunction (POCD). Thus, we hypothesized that inhibition of mTOR signaling could affect the occurrence of POCD. Methods and results: Here, 12-14-week-old C57BL/6J mice were randomly divided into four groups. Conditioned fear tests on all mice were carried out on postoperative day 1. The expression levels of mTOR and LC3B proteins in the hippocampus were evaluated by western blotting and immunofluorescence assay. The conditioned fear tests showed that rapamycin could improve the learning and memory of mice. Rapamycin reduced the level of p-mTOR (Ser2448) protein in the hippocampus (P< 0.05 vs Sur group) and increased the content of LC3B protein in the hippocampus (P< 0.05 vs Sur group). Immunofluorescence assay showed that LC3B was mainly expressed in the cytoplasm. Conclusions: The mTOR inhibitor rapamycin can significantly impede mTOR signaling, up-regulate the expression of LC3B protein in the hippocampus, and improve cognitive dysfunction caused by surgical trauma.
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关键词
Postoperative cognitive dysfunction, mammalian target of rapamycin, autophagy, rapamycin
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