The impacts of acupuncture on cognitive function and neuroinflammation in vascular dementia rats by regulating the HMGB1-RAGE signal axis
Objective To investigate the impacts of acupuncture on cognitive function,neuroinflammation and the high mobility group box-1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway in vascular dementia(VD)rats.Methods A total of 72 adult male Sprague-Dawley(SD)rats were randomly divided into the control group,model group,treatment group and inhibitor group,with 18 rats per group,and the VD model was established except rats in the control group.Except for the inhibitor group,oral gavage of 0.9%NaCl solution daily for consecutive 2 weeks was performed in the other groups.Acupuncture was additionally given to rats of treatment group,and oral gavage of glycyrrhizic acid 3 mg/mL once daily was given to rats of inhibitor group for consecutive 2 weeks.Morris water maze test was performed to record the mean escape latency,cumulative distance to the platform,time spent to first reach the platform and number of platform crossings.The enzyme-linked immunosorbent assay(ELISA)was conducted to measure serum tumor necrosis factor alpha(TNF-α),interleukin-1 beta(IL-1β),IL-10 and transforming growth factor beta(TGF-β).The hematoxylin and eosin(HE)staining was applied to observe the morphological changes in the CA1 region of the rat hippocampus.The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining was applied to detect neuronal apoptosis in the hippocampal CA1 region.Immunofluorescence was applied to detect the activation of microglia.Western blot was applied to detect the expression levels of B-cell lymphoma factor 2(Bel-2),Bel-2 associated X protein(Bax),HMGB1,and RAGE.Results Compared with those of the control group,rats in the model had significantly longer mean escape latency,cumulative distance to the platform and time spent to first reach the platform,less number of platform crossings,higher serum TNF-α and IL-1β,lower serum IL-10 and TGF-β,severer damage in the hippocampal CA1 region,higher apoptotic rate in neurons,less number of neurons,greater number of microglia,higher positive rates of ionized calcium-binding adaptor molecule 1(IBA-1)and CD68(microglia markers)in the hippocampus,higher protein levels of Bax,HMGB1 and RAGE,and lower protein level of Bel-2 in the hippocampus(all P<0.05).In comparison to the model group,the opposite results were obtained in the treatment and inhibitor groups(all P<0.05).Conclusion Acupuncture can improve the cognitive impairment of VD rats and alleviate neuroinflammatory reaction by inhibiting the HMGB1-RAGE signaling pathway.
Vascular dementiaRatAcupunctureHigh mobility group proteinsReceptor for advanced glycation end productsCognitive impairmentAnimal experiment