养阴宁神方对去势小鼠海马神经元突触的可塑性调节OACSTPCD

Objective To observe the effects of Yangyin Ningshen Formula(YYNSF)on cognitive function in ovariectomized female mice.Methods Sixty C57BL/6J female mice were randomly divided into sham-operated group,model group,estrogen group,and low-,medium-,and high-dose YYNSF groups,with 10 mice in each group.Sham-operated group underwent skin and peritoneal incision without removing the ovaries,while the rest groups were subject to bilateral ovariectomy.Sham-operated and model groups were given equal volume of saline(0.1 ml/10 g),while estrogen group[estradiol(E2),0.09 mg/kg],and low-(9.459 g/kg),medium-(18.459 g/kg),and high-dose(36.99 g/kg)YYNSF groups were given corresponding medications.All groups were treated by gavage for three weeks.The wound healing time after surgery was recorded.Morris water maze with recording latency and cross times were carried out before ovariectomy,one week and four weeks after ovariectomy respectively,in order to assess the learning and memory function of the mice.ELISA was used to measure the level of serum E2;HE staining was performed to observe morphology of the hippocampal neurons;Nissl staining was used to observe the number of Nissl-positive cells in the hippocampus;confocal microscopy was used to observe the ultrastructures in the hippocampal neurons.Results The wound healing time of model group was longer than that of sham-operated group(P<0.05).Compared with model,estrogen,and low-and high-dose YYNSF groups,the wound healing time of medium-dose YYNSF group was shortened(P<0.05).The Morris water maze test revealed that compared with sham-operated group,all other groups showed prolonged escape latency and reduced cross times at one week after ovariectomy(P<0.05).At four weeks after ovariectomy,model group showed prolonged escape latency and reduced cross times compared with sham-operated group(P<0.05).Compared with model group,estrogen and low-,medium-,and high-dose YYNSF groups showed shorter escape latency and more cross times(P<0.05).Compared with sham-operated group,E2 level in model group decreased significantly at four weeks after ovariectomy(P<0.01);while compared with model group,E2 level in estrogen and low-,medium-,and high-dose YYNSF groups increased significantly(P<0.01).Compared with sham-operated group,Nissl staining demonstrated a decrease in the number of Nissl-positive cells in the hippocampus of model group(P<0.01);while compared with model group,the number of Nissl-positive cells in the hippocampus of estrogen and low-,medium-,and high-dose YYNSF groups showed an increase(P<0.01).HE staining showed increased pyramidal neurons and their dendritic synapses in sham-operated,estrogen,and low-,medium-,and high-dose YYNSF groups,and fewer pyramidal neurons and more granule cells in model group.Confocal microscopy showed increased synaptic vesicles and rough endoplasmic reticula in the hippocampal neurons of sham-operated,estrogen,and low-,medium-,and high-dose YYNSF groups,and decreased synapses and their vesicles in the hippocampal neurons of model group.Conclusion YYNSF may exert protective effects on the brain by increasing plasma E2 level,improving synaptic morphology and plasticity of the hippocampal neurons,and enhancing cognitive function of the ovariectomized mice.