Electroacupuncture Improves Blood-Brain Barrier and Hippocampal Neuroinflammation in SAMP8 Mice by Inhibiting HMGB1/TLR4 and RAGE/NADPH Signaling Pathways / 中国结合医学杂志

OBJECTIVE@#To investigate the molecular mechanisms underlying the beneficial effect of electroacupuncture (EA) in experimental models of Alzheimer's disease (AD) in vivo.@*METHODS@#Senescence-accelerated 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 SAMP8 mice 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 SAMP8 mice, 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) signaling pathways (P<0.01).@*CONCLUSION@#EA may potentially improve cognitive impairment in AD via inhibition of fibrin/A β deposition and deactivation of the HMGB1/TLR4 and RAGE/NADPH signaling pathways.

Association between fatty liver disease and lacunar infarction / 临床肝胆病杂志

ObjectiveTo investigate whether fatty liver disease is a risk factor for lacunar infarction. MethodsA retrospective analysis was performed for the clinical data of 457 patients with lacunar infarction (lacunar infarction group) and 120 control patients, who were hospitalized in our hospital from 2007 to 2017, to analyze whether fatty liver disease is a risk factor for lacunar infarction. The chi-square test was used for comparison of categorical data between groups, and the t-test was used for comparison of continuous data between groups. Univariate and multivariate regression analyses were used to screen out the risk factors for lacunar infarction. ResultsThe lacunar infarction group had a significantly higher incidence rate of fatty liver disease than the control group (60.39% vs 39.17%, χ2=17.379, P＜0.001). The multivariate regression analysis showed that after adjustment for age, sex, smoking, drinking, hypertension, and diabetes, fatty liver disease was an independent risk factor for lacunar infarction (odds ratio ［OR］=1.96, 95% confidence interval ［CI］: 1.21-3.02, P=0.003). There was a significant interaction between obesity and fatty liver disease (P=0.001). Non-obese fatty liver disease was an independent risk factor for lacunar infarction (OR=3.29, 95% CI: 1.55-7.23, P＜0.001); however, in the obese subgroup, obese fatty liver disease was not an independent risk factor for lacunar infarction(P=0532)，Age(OR=6.67,95%CI:1.98~121.56,P＜0001), hypertension (OR=638,95%CI:512~12.06,P＜0001) were independent risk factors for lacunar infarction. ConclusionNon-obese fatty liver disease is an independent risk factor for lacunar infarction.