标题：miR-34a Inhibitor May Effectively Protect against Sevoflurane-Induced Hippocampal Apoptosis through the Wnt/beta-Catenin Pathway by Targeting Wnt1
作者：Zhao, Xiaoling; Sun, Yue; Ding, Yongbo; Zhang, Jun; Li, Kezhong
作者机构：[Zhao, Xiaoling] Shandong Univ, Sch Med, Jinan, Shandong, Peoples R China.; [Zhao, Xiaoling; Ding, Yongbo; Zhang, Jun; Li, Kezhong] Yantai Yuhuangdi 更多
通讯作者地址：[Li, KZ]Yantai Yuhuangding Hosp, Dept Anesthesiol, 20,Yundong Rd, Yantai 264000, Shandong, Peoples R China.
来源：YONSEI MEDICAL JOURNAL
关键词：miR-34a; sevoflurane; hippocampal apoptosis; Wnt1; Wnt/beta-catenin; pathway
摘要：Purpose: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. mill-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear:; Materials and Methods: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. mill-34a expression was reduced through intracerebroventricular injection with mill-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/beta-catenin pathway-related proteins were evaluated using Western blot analysis.; Results: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-Ma inhibited the Wnt/beta-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects.; Conclusion: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/beta-catenin pathway by targeting Wnt1.