To explore the neuroprotective effect of electroacupuncture on cerebral ischemic stroke
(CIS) in rats and its associated mechanism with cell pyroptosis mediated by the NLRP3/Caspase-1 inflammatory
pathway. Methods: A total of 48 SPF-grade SD rats were randomly divided into four groups: the
sham-operation group, the middle cerebral artery occlusion (MCAO) model group, the electroacupuncture group,
and the inhibitor (MCC950) group, with 12 rats in each group. A rat cerebral ischemia-reperfusion model was
established using the modified Zea-Longa method. The electroacupuncture group received electroacupuncture
intervention starting on the first day after modeling, once a day for 14 days. The inhibitor group was
administered an intraperitoneal injection of MCC950 (3 mg/kg) during the same period, once a day for 14 days.
The sham-operation group and the model group received no intervention. The degree of neurological deficit was
evaluated using the Zea Longa 5-point neurological function score. The cerebral infarction volume was detected
by TTC staining, and the survival status of neurons was observed by Nissl staining. The mRNA and protein
expression levels of NLRP3, GSDMD, and their downstream Caspase-1, IL-1β, and IL-18 in brain tissue were
detected using immunohistochemistry, immunofluorescence, real-time fluorescent quantitative PCR (qPCR),
enzyme-linked immunosorbent assay (Elisa), and Western blot (WB) techniques. Results: Compared with the
sham-operation group, the neurological deficit score of rats in the model group was significantly increased (P<
0.001), the cerebral infarction volume was significantly enlarged (P<0.001), the number of Nissl bodies
decreased, and neuronal morphology was damaged. The mRNA and protein expressions of NLRP3, GSDMD,
Caspase-1, IL-1β, and IL-18 were all significantly upregulated (P<0.01 or P<0.001). Compared with the model
group, the above indicators in the electroacupuncture group and the inhibitor group were significantly improved:
the neurological function score decreased (P<0.05 or P<0.001), the cerebral infarction volume decreased (P<
0.001), the number of Nissl bodies increased, and neuronal morphology was more intact (P<0.001). The mRNA
and protein expression levels of NLRP3, GSDMD, and their downstream inflammatory factors were significantly
decreased (P<0.05, P<0.01, or P<0.001). Moreover, there were no statistical differences in the various indicators between the
electroacupuncture group and the inhibitor group (P>0.05). Conclusion: Electroacupuncture can inhibit the activation of the NLRP3/
Caspase-1 inflammatory pathway, downregulate the expression of cell pyroptosis-related proteins (NLRP3, GSDMD) and downstream
pro-inflammatory factors (Caspase-1, IL-1 β, IL-18), reduce neuroinflammatory damage after cerebral ischemia-reperfusion, decrease
cerebral infarction volume, and improve neurological function. Its neuroprotective effect is comparable to that of NLRP3 inhibitor
intervention.
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