Efficacy of acupuncture in animal models of vascular dementia: A systematic review and network meta-analysis

Abstract

Background and purpose: Acupuncture is widely used in clinical practice for the treatment of vascular diseases. However, the protocol, efficacy, and mechanism of acupuncture in animal models of vascular dementia are still controversial. Based on the above problems, we initiated this comprehensive study.

Methods: To analyze the literatures included in this study, 4 databases were searched and the SYRCLE's Risk of bias tool was employed. To perform the subgroup analysis of different acupuncture methods and the Review Manager 5.3 was applied. Meanwhile, the pairwise and network meta-analysis were conducted using Addis 1.16.8. The outcomes included escape latency, number of crossings, time spent in the target quadrant, and swimming speed.

Results: Forty-two studies with a total of 1,486 animals were included in this meta-analysis. According to the results from subgroup analysis, GV20 + ST36 (Baihui + bilateral Zusanli) combined with 14-day manual acupuncture can obtain best improvement of the rats cognitive function among all acupuncture regimens (MD: -23.41; 95%CI: -26.66, -20.15; I² = 0%; P < 0.001). The heterogeneity of other acupuncture treatments was significantly higher than that of GV20 + ST36, because the treatment courses were not uniform. Pair-wise and network comparisons are highly consistent. The major results of the network meta-analysis were as follows, In comparison to the impaired group, the acupuncture group showed significantly reduced escape latency (MD: -25.87; 95%CI: -30.75, -21.12), increased number of original platform crossings (MD: 2.63; 95%CI: 1.94, 3.34) and time spent in the target quadrant (MD: 7.88; 95%CI: 4.25, 11.44). The overall results of the network meta-analysis are as follows: the normal and sham-operated groups performed the best, followed by medicine and acupuncture, while no effect was found in the impaired group treated with non-acupoint and palliative.

Conclusions: Acupuncture significantly improves cognitive function in rats with vascular dementia. Compared to other acupuncture plans, (GV20 + ST36, MA) and 14 -day manual acupuncture can be used to obtain better results. The main mechanism of acupuncture in the treatment of vascular dementia is reduced oxidative stress, neuronal inflammation, and apoptosis, as well as the increased synaptic plasticity and neurotransmitters.

Systematic review registration: https://inplasy.com/inplasy-2021-11-0036/, identifier: INPLASY2021110036.

Keywords: acupuncture; acupuncture mechanism; acupuncture protocol; animal studies; morris water maze; network meta-analysis; vascular dementia.

Figure 1

Study characteristics. (A) Methods of surgical modeling, (B) Total number of modeling and the number of successful modeling, (C) Frequency of acupoint use, (D) Total course of treatment, (E) Frequency of acupoint combination. 2VO, Two - Vessel Occlusion or Bilateral Common Carotid Artery Occlusion; 4VO, Four-Vessel Occlusion; MCAO, Middle Cerebral Artery Occlusion; EO, Embolic occlusion, *P < 0.05 (Modeling success rate of MCAO VS 2VO, EO and 4VO, MCAO had the highest success rate). ^#P < 0.05 (Modeling success rate of 2VO VS 4VO and EO VS 4VO, no difference between 2VO and EO, and the lowest is 4VO).

Figure 2

Network graph of morris water maze. Escape latency (A), Number of crossings (B), Time spent in target quadrant (C), Swimming speed (D). Gn, Normal group; Gs, Sham-operated group; Gi, Impaired group; Ga, acupuncture group; Gna, Non-acupoint group; Gm, Medicine group.

Figure 3

Rank probability of interventions. Escape latency (A), Number of crossings (B). Gn, Normal group; Gs, Sham-operated group; Gi, Impaired group; Ga, acupuncture group; Gna, Non-acupoint group; Gm, Medicine group.

Figure 4

The main mechanism of acupuncture in animal models of VD. EA, electroacupuncture; MA, manual acupuncture. Synapse function: LTP (Long-term Potential), AVP (arginine vasopressin), β-EP (β-endorphine), SS (somatostatin), ACh (acetylcholine), HVA (homovanillic acid), DA (dopamine), DOPAC (Dihydroxyphenylaceticacid), 5-HT (5-hydroxytryptamine),EP (Epinephrine), nAChR (Nicotinic-Acetylcholine receptor), D1/D5R (dopamine 1/ dopamine5 receptor), NMDAR (N-methyl-D-aspartate receptor), AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor), GABA_AR (γ-amino-butyric acid type A receptor), 5-HT_1AR (postsynaptic serotonin (1A) receptors), PSD-95 (postsynaptic density-95). signal pathways: CBF (cerebral blood flow), Ang-1 (Angiopoietin-1), VEGF (vascular endothelial growth factor), TLR4 (Toll Like Receptor 4), MyD88 (myeloid differentiation factor 88), NF-κB (nuclear factor-kappa B), α7nAChR (alpha-7 nicotinic acetylcholine receptor), JAK2 (Janus Kinase 2), STAT3 (Signal Transducer and Activator of Transcription 3), TNF-α (Tumor Necrosis Factor-α), IL-4 (interleukin 4), IL-10 (interleukin 10), IL-1β (interleukin 1β), Nrf2 (Nuclear factor erythroid2-related factor2), ARE (antioxidant response element), HO-1 (heme oxygenase), NQO1 (NADP (H) quinone oxidoreductase), ROS (reactive oxygen species), MDA (Malon-dialdehyde), SOD (superoxide dismutase), GSH (glutathione), HMGB1 (mobility group protein B1), MMP (mitochondrial membrane potential), PI3K (phosphatidylinositol 3-kinase), AKT (protein kinase B), mTOR (mammalian target of rapamycin), Bcl-2 (B-cell lymphoma-2), JNK (c-Jun N-terminal kinase).