PDF(Pubmed)
Abstract：
Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients. Liraglutide (LRG) has high homology (97%) with natural glucagon like peptide-1, and it has been proved to be effective in some nervous system diseases. Whether LRG could regulate POCD has not been reported.
Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively.
LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis.
LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.
Sevoflurane (Sev) was used to simulate postoperative cognitive dysfunction (POCD) model. Morris water maze test was performed to evaluate the memory ability and neurological function of rats. Escape latency, swim distance, crossing platform times, average velocity, and targeting quadrant time were analyzed. The cell apoptosis, mRNA and protein expression were measured through flow cytometry, PCR, and western blotting, respectively.
LRG significantly improved the memory ability and neurological function of Sev-treated rats, but 3-MA reversed the effects of LRG. LRG remarkably inhibited apoptosis but up-regulated autophagy related proteins both in vivo and in vitro levels. However, knocking down AMPK could markedly reverse the influence of LRG on apoptosis, autophagy, and cell apoptosis.
LRG induced autophagy activation can maintain cell homeostasis and promote cell survival by blocking the apoptotic pathway. LRG could improve Sev-induced POCD via activating autophagy, inhibiting apoptosis, and regulating AMPK/mTOR signaling pathway. This study provides a novel therapeutic strategy for the prevention and treatment of POCD.
摘要：
背景：术后认知功能障碍（POCD）是老年患者常见的术后并发症。利拉鲁肽(LRG)与天然胰高血糖素样肽-1具有很高的同源性(97%),已被证明对某些神经系统疾病有效。尚未报道LRG是否可以调节POCD。
方法：采用七氟醚（Sev）模拟术后认知功能障碍（POCD）模型。采用Morris水迷宫实验评价大鼠记忆能力和神经功能。逃避延迟，游泳距离,穿越平台次数,平均速度,并对靶向象限时间进行了分析。细胞凋亡，通过流式细胞术检测mRNA和蛋白表达,PCR,和西方印迹，分别。
结果：LRG显著改善Sev处理大鼠的记忆能力和神经功能，但3-MA逆转了LRG的影响.LRG显著抑制细胞凋亡，但在体内和体外水平上调自噬相关蛋白。然而,敲低AMPK可以显著逆转LRG对细胞凋亡的影响,自噬,和细胞凋亡。
结论：LRG诱导的自噬激活可通过阻断凋亡途径维持细胞稳态，促进细胞存活。LRG可以通过激活自噬改善Sev诱导的POCD，抑制细胞凋亡，调节AMPK/mTOR信号通路。本研究为POCD的预防和治疗提供了新的治疗策略。
方法：采用七氟醚（Sev）模拟术后认知功能障碍（POCD）模型。采用Morris水迷宫实验评价大鼠记忆能力和神经功能。逃避延迟，游泳距离,穿越平台次数,平均速度,并对靶向象限时间进行了分析。细胞凋亡，通过流式细胞术检测mRNA和蛋白表达,PCR,和西方印迹，分别。
结果：LRG显著改善Sev处理大鼠的记忆能力和神经功能，但3-MA逆转了LRG的影响.LRG显著抑制细胞凋亡，但在体内和体外水平上调自噬相关蛋白。然而,敲低AMPK可以显著逆转LRG对细胞凋亡的影响,自噬,和细胞凋亡。
结论：LRG诱导的自噬激活可通过阻断凋亡途径维持细胞稳态，促进细胞存活。LRG可以通过激活自噬改善Sev诱导的POCD，抑制细胞凋亡，调节AMPK/mTOR信号通路。本研究为POCD的预防和治疗提供了新的治疗策略。
