OBJECTIVETo establish a mouse model for human chronic HBV infection, and to investigate the role of PD-1/PD-L1 signaling pathway in antiviral immunity.

METHODSA mouse model was established by hydrodynamic injection of the plasmid pAAV/HBV1.2-GFP into the tail vein of C57BL/6 mice, HBV markers were assayed at different time points after injection. After intraperitoneal injection of anti-PD-L1 monoclonal antibody, the serum ALT, and HBV DNA in the serum, liver and kidney were assayed.

RESULTSThe chronic HBV infection mouse model were established successfully, serum HBsAg and high load of HBV DNA were detectable 90 days after plasmid injection. After blocking of the PD-1/PD-L1 pathway, the serum ALT level of mice were significantly increased (P < 0.01), and the HBV DNA load in serum (P < 0.01), liver (P < 0.05) and kidney (P < 0.05) were decreased significantly.

CONCLUSIONBlocking the PD-1/PD-L1 signaling pathway can enhance antiviral response in mice with chronic HBV infection.

Animals ; Antigens, Surface ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; B7-1 Antigen ; metabolism ; B7-H1 Antigen ; DNA, Viral ; analysis ; Disease Models, Animal ; Hepatitis B virus ; metabolism ; Hepatitis B, Chronic ; immunology ; metabolism ; virology ; Male ; Membrane Glycoproteins ; metabolism ; Mice ; Mice, Inbred C57BL ; Peptides ; metabolism ; Programmed Cell Death 1 Receptor ; Signal Transduction

OBJECTIVETo investigate the effect of total fiavonoids from Chrysanthemun morifolium (TFCM) on learning and memory, and cholinergic system function in aging mice.

METHODSThe aging mice model was established by subcutaneous injection of D-galactose. ICR mice were divided into five groups (n=10): contrA group, model group, and TFCM groups. Mice in TFCM groups were given TFCM (50,100 or 150 mg/kg) by gastric irrigation once a day. Learning and memory ability were evaluated by Morris water maze test. The MDA content, SOD and Ach E activity were also measured.

RESULTSCompared with control group, learning and memory ability declined in the D-galactose-induced aging mice; meanwhile MDA content and AchE activity increased, SOD activity decreased. Treatment with TFCM (100, 150 mg/kg) ameliorated the decrease in learning and memory ability of aging mice. Compared with model group, TFCM (100, 150 mg/kg) could also decrease MDA content and Ach E activity, and increase SOD activity in aging mice.

CONCLUSIONTFCM may improve the learning and memory ability of aging mice. The mechanism is involved in its antioxidative characteristic and improvement of central cholinergic system function.

Aging ; drug effects ; physiology ; Animals ; Antioxidants ; pharmacology ; Cholinergic Fibers ; physiology ; Cholinergic Neurons ; physiology ; Chrysanthemum ; chemistry ; Female ; Flavonoids ; isolation & purification ; pharmacology ; Learning ; drug effects ; Male ; Memory ; drug effects ; Mice ; Mice, Inbred ICR

Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; CD8-Positive T-Lymphocytes ; metabolism ; Case-Control Studies ; Female ; Hepatitis B, Chronic ; blood ; Humans ; Middle Aged ; Programmed Cell Death 1 Receptor ; Up-Regulation ; Young Adult