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. 2021 Apr 19:2021:8842022.
doi: 10.1155/2021/8842022. eCollection 2021.

Electroacupuncture Attenuates Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion via miR-137/NOX4 Axis

Xiaochen Bi  1 , Yanfei Feng  2 , Zemin Wu  3 , Jianqiao Fang  4
Affiliations

Electroacupuncture Attenuates Cognitive Impairment in Rat Model of Chronic Cerebral Hypoperfusion via miR-137/NOX4 Axis

Xiaochen Bi et al. Evid Based Complement Alternat Med. .

Abstract

Electroacupuncture has shown protective effects on cognitive decline. However, the underlying molecular mechanisms are not clear. The present study was conducted to determine whether the cognitive function was ameliorated in cerebral hypoperfusion rats following electroacupuncture and to investigate the role of miR-137/NOX4 axis. In this study, chronic cerebral hypoperfusion (CCH) model was established by bilateral common carotid artery occlusion. Electroacupuncture treatment attenuated brain injury in CCH model group via regulating miR-137/NOX4 axis. Furthermore, the data of neuronal apoptosis and oxidative stress were observed. Our findings indicated that (1) neuronal apoptosis and oxidative stress in CCH rats were significantly increased compared with control group; (2) the animal cognitive performance was evaluated using the Morris water maze (MWM). The results showed that electroacupuncture therapy ameliorated spatial learning and memory impairment in cerebral hypoperfusion rats; and (3) electroacupuncture therapy reduces neuronal apoptosis and oxidative stress by activating miR-137/NOX4 axis. These results suggest that electroacupuncture therapy for CCH may be mediated by miR-137/NOX4 axis. Electroacupuncture therapy may act as a potential therapeutic approach for chronic cerebral hypoperfusion.

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Conflict of interest statement

The authors declare that there are no conflicts of interest in the publication of this manuscript.

Figures

Figure 1
Figure 1
The interaction between miR-137 and NOX4. (a) The relative expression of miR-137 in the sham, model, and electroacupuncture groups, respectively. (b) The expression of NOX proteins in the sham, model, and electroacupuncture groups, respectively. (c) The interaction between miR-137 and NOX4 was predicted on ENCORI databases. (d) The interaction between miR-137 and NOX4 was detected by dual luciferase experiments. Data were normalized to the control and presented as mean ± SD, ∗∗p < 0.01.
Figure 2
Figure 2
Electroacupuncture therapy inhibited neuronal apoptosis. The number of apoptosis cells in rat brain was detected by TUNEL.
Figure 3
Figure 3
The expression of GFAP and NOX4. (a) The expression of glial fibrillary acidic protein (GFAP) (green) and NOX4 (red) in the hippocampus of rats by immunofluorescence. (b) The relative expression of NOX4 mRNA by qRT-PCR. (c) The content of NOX4 was detected by ELISA. The error bars are presented as mean ± SD, ∗∗p < 0.01.
Figure 4
Figure 4
The expression of eNOS and iNOS. (a) The relative expression of eNOS mRNA. (b) The relative expression of iNOS mRNA. (c) The expression of eNOS and iNOS protein. At least three repeats were carried out, and the mean ± SD is presented, ∗∗p < 0.01.
Figure 5
Figure 5
The oxidative stress in rat. (a) The content of ROS. (b) The content of MDA. (c) The content of SOD. (d) The relative expression of CAT. ROS, MDA, SOD, and CAT were detected by ELISA. At least three repeats were carried out, and the mean ± SD is presented, ∗∗p < 0.01.
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