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Summary: Aims: Acupuncture has been reported to affect vascular dementia through a variety of molecular mechanisms. An isobaric tag for relative and absolute quantification (iTRAQ) with high‐resolution liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analyses makes it possible to attain a global profile of proteins. Hence, we used an iTRAQ‐LC‐MS/MS strategy to unravel the underlying mechanism of acupuncture. Methods: Wistar rats were subjected to vascular dementia with bilateral common carotid occlusion. Acupuncture was intervened for 2 weeks at 3 days after surgery. The Morris water maze was used to assess the cognitive function. Proteins were screened by quantitative proteomics and analyzed by bioinformatic analysis. Four differentially expressed proteins (DEPs) were validated by western blot. The reactive oxygen species (ROS) production, neuron cell loss, and long‐term potentiation (LTP) were determined after western blot. Results: Acupuncture at proper acupoints significantly improved cognitive function. A total of 31 proteins were considered DEPs. Gene ontology (GO) analysis showed that most of the DEPs were related to oxidative stress, apoptosis, and synaptic function, which were regarded as the major cellular processes related to acupuncture effect. Western blot results confirm the credibility of iTRAQ results. Acupuncture could decrease ROS production, increase neural cell survival, and improve LTP, which verified the three major cellular processes. Conclusion: Acupuncture may serve as a promising clinical candidate for the treatment of vascular dementia via regulating oxidative stress, apoptosis, or synaptic functions. [ABSTRACT FROM AUTHOR]

Aims Oxidative stress and inflammation have been implicated in the pathogenesis of vascular dementia (VD). Thioredoxin-interacting protein (TXNIP) plays a vital role in oxidative stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation. There is evidence that acupuncture has an antioxidative and neuroprotective effect in VD. In this study, we investigated whether acupuncture can attenuate cognitive impairment via inhibiting TXNIP-associated oxidative stress and inflammation in VD rats. Methods Both common carotid arteries were occluded (2-vessel occlusion [2VO]) in rats to model VD. The neuroprotective effect of acupuncture was assessed by the Morris water maze and Nissl staining. Oxidative stress was assessed by detecting levels of reactive oxygen species, DNA oxidation, and antioxidase. Western blot, real-time PCR, and immunofluorescence were used to detect the expression of TXNIP, NLRP3, caspase-1, and IL-1β. A TXNIP siRNA intraventricular injection was applied to investigate whether acupuncture mimicked the effect of TXNIP inhibitor. Results Our findings demonstrated that VD rats treated with acupuncture had reduced hippocampal neuronal loss and oxidative stress. The upregulation of TXNIP, NLRP3, caspase-1, and IL-1β induced by 2VO was also reversed by acupuncture. Furthermore, TXNIP siRNA had a similar effect as acupuncture on cognition, hippocampal neurons, and ROS production in VD rats. Conclusion In conclusion, our study suggests that the neuroprotective effects of acupuncture in VD are mediated through reducing expression of TXNIP-associated oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]