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MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1

[ Vol. 16 , Issue. 4 ]

Author(s):

Jun Xiong, Huijun Wang, Feng Mu, Zhanxue Liu, Yin Bao and Yongxing Sun*   Pages 382 - 391 ( 10 )

Abstract:


Purpose: Research has shown that exposure to anesthesia might increase the risks of cognitive impairments and learning difficulties. MiR-125b-5p contributed to anesthesia-induced hippocampal apoptosis. However, the role of miR-125b-5p in sevoflurane-induced cognitive impairments remains unclear.

Methods: Firstly, sevoflurane was used to establish a rat model and cognitive impairment was detected by the Morris water maze (MWM) test. The hippocampus was observed by HE staining. The lentivirus-miR-125b-5p antagomiR was transfected into rats to decrease miR-125b-5p. The interaction between miR-125b-5p and LIM domain kinase 1 (LIMK1) was confirmed by the luciferase reporter assay. The mRNA and expression levels of related genes and mRNA were examined by the Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot.

Results: Sevoflurane induced the cognitive dysfunction presenting with longer latency time and few platform crossings in rats. Moreover, miR-125b-5p was observed to be up-regulated in both sevoflurane-anesthesia rats and sevoflurane-treated SH-SY5Y cells. More importantly, a decrease in miR-125b-5p could prevent sevoflurane-induced hippocampal apoptosis and inflammation in rats. Moreover, LIMK1 was the target gene of miR-125b-5p. Interestingly, si-LIMK1 could restore the sevoflurane-induced cell apoptosis in SH-SY5Y cells, which was alleviated by miR-125b-5p inhibitor. Finally, the miR-125b-5p inhibitor shortened the time to find the platform and increased the number of platform crossings compared to sevoflurane-anesthesia rats in the Morris water maze test. At the same time, the expression of LIMK1 was dramatically increased.

Conclusion: Altogether, these findings suggested that miR-125b-5p inhibitor could protect against the sevoflurane-induced cognitive impairments by targeting LIMK1.

Keywords:

Sevoflurane, miR-125b-5p, cognitive impairments, LIMK1, Morris Water Maze (MWM), SH-SY5Y.

Affiliation:

Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing City, 100093, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing City, 100730, Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing City, 100093, Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing City, 100093, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing City, 100730, Department of Anesthesiology, Sanbo Brain Hospital, Capital Medical University, Beijing City, 100093



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