摘要
Objective: To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture(EA) in experimental models of Alzheimer’s disease(AD) in vivo. Methods: Senescenceaccelerated mouse prone 8(SAMP8) mice were used as AD models and received EA at Yingxiang(LI 20, bilateral) and Yintang(GV 29) points for 20 days. For certain experiments, SAMP8 mice were injected intravenously with human fibrin(2 mg). The Morris water maze test was used to assess cognitive and memory abilities. The changes of tight junctions of blood-brain barrier(BBB) in mice were observed by transmission electron microscope. The expressions of fibrin, amyloid-β(Aβ), and ionized calcium-binding adapter molecule 1(IBa-1) in mouse hippocampus(CA1/CA3) were detected by reverse transcription-quantitative polymerase chain reaction(qRT-PCR), Western blot or immunohistochemical staining. The expression of fibrin in mouse plasma was detected by enzyme-linked immunosorbent assay. The expressions of tight junction proteins zonula occludens-1 and claudin-5 in hippocampus were detected by qRT-PCR and immunofluorescence staining.Apoptosis of hippocampal neurons was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) staining. Results: Fibrin was time-dependently deposited in the hippocampus of SAMP8mice and this was inhibited by EA treatment(P<0.05 or P<0.01). Furthermore, EA treatment suppressed the accumulation of Aβ in the hippocampus of SAMP8 mice(P<0.01), which was reversed by fibrin injection(P<0.05 or P<0.01). EA improved SAMP8 mice cognitive impairment and BBB permeability(P<0.05 or P<0.01).Moreover, EA decreased reactive oxygen species levels and neuroinflammation in the hippocampus of SAMP8mice, which was reversed by fibrin injection(P<0.05 or P<0.01). Mechanistically, EA inhibited the promoting effect of fibrin on the high mobility group box protein 1(HMGB1)/toll-like receptor 4(TLR4) and receptor for advanced glycation end products(RAGE)/nicotinamide adenine dinucleotide phosphate(NADPH
基金
Supported by the National Natural Science Foundation of China (No.82074552)
Shaanxi Science and Technology Department Project (No.2018JM7041)
Shaanxi Province TCM "Double Chain Integration" Young and Middle-Aged Scientific Research Innovation Team Construction Project (No.2022-SLRH-LJ-012)。
