Electroacupuncture Ameliorates RVLM Neuronal Injury in Spontaneously Hypertensive Rats via PI3K/Akt Pathway: Insights From Transcriptomic Analysis

Abstract

Background

Essential hypertension represents a widespread global health challenge, frequently associated with vascular structural changes and neuronal damage. Electroacupuncture (EA) has demonstrated promise in reducing blood pressure and promoting neuronal integrity. Nevertheless, the exact molecular pathways involved have not been comprehensively characterized. This study was designed to elucidate how EA exerts its antihypertensive effects by integrating transcriptomic profiling with functional evaluation.

Methods

Four experimental groups were established: Wistar Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), EA-treated SHRs, and a non-acupoint sham control group. EA stimulation was applied at LI11 and LR3 acupoints over a 15-day period. Blood pressure and heart rate were recorded at several time points. Neuronal structural integrity was evaluated via hematoxylin–eosin (HE) and Nissl staining. RNA sequencing and qPCR were employed to detect and confirm differentially expressed genes (DEGs). Enrichment analysis based on Gene Ontology (GO) and Genes and Genomes (KEGG) databases was applied to characterize the biological processes and signaling pathways involved. Western blot and immunohistochemical assays further verified the participation of the PI3K/Akt pathway.

Results

In SHR, EA administration led to significant decreases in systolic blood pressure and cardiac rate. Histological examination indicated enhanced neuronal morphology in the rostral ventrolateral medulla (RVLM) following EA, accompanied by reduced plasma angiotensin II (Ang II) and norepinephrine (NE) concentrations, as well as suppressed renal sympathetic nerve activity. Transcriptomic profiling identified 384 DEGs in SHRs relative to WKY rats, of which 15 were restored toward normal levels by EA. GO and KEGG analyses highlighted the PI3K/Akt signaling pathway as a pivotal mediator. Subsequent qPCR and Western blot validation confirmed that EA-regulated essential components of this pathway, such as PI3K, Akt, and phosphorylated Akt, within the RVLM.

Conclusion

EA likely produces its antihypertensive influence in SHRs by modulating Ang II concentrations, conferring neuroprotection, and attenuating sympathetic outflow. These results underscore the central involvement of the PI3K/Akt signaling cascade in EA-induced blood pressure regulation, offering fresh perspectives into its mechanistic basis. Comparative transcriptomic assessment has uncovered a promising new target through which EA may ameliorate neuronal impairment in the RVLM of hypertensive rats.

Keywords

electroacupuncture spontaneously hypertensive rats rostral ventrolateral medulla (RVLM)PI3K/Akt signaling pathway transcriptomic analysis neuroprotection

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