Effect of Gouteng Jiangya Jieyu Formula(钩藤降压解郁方)on the Ultrastructure of Hippocampal Synapses and the Expression of TLR4,NF-κB p65 and NLRP3 Proteins of Hippocampus in Rats of Hypertension Complicated with Depression
Objective:To observe the effect of Gouteng Jiangya Jieyu Formula(GTJYJYF)on the learning-memory function,ultrastructure of hippocampal synapses,inflammatory response in the hippocampus as well as the expression of hippocampal TLR4,NF-κB p65 and NLRP3 proteins in spontaneously hypertensive rats complicated with depression.Methods:Totally 35 SHR rats were randomly divided into model group,positive control group[amlodipine besylate(0.45 mg/kg)+fluoxetine hydrochloride(1.80 mg/kg)],GTJYJYF low-dose group(6.35 g/kg),GTJYJYF medium-dose group(12.69 g/kg)and GTJYJYF high-dose group(25.38 g/kg),with an additional blank control group consisting of 7 Sprague-Dawley rats.The SHR rats were induced to develop hypertension complicated with depression using chronic unpredictable stress combined with isolation rearing.The modeling process involved oral administration once daily for 6 weeks.Tail arterial systolic and diastolic pressures were measured using a non-invasive blood pressure meter.Morris water maze test was conducted to evaluate learning and memory abilities.Transmission electron microscopy was used to observe the ultrastructure of hippocampal synapses.The levels of inflammatory factors(IL-1βand IL-18)in the hippocampus were measured by enzyme-linked immunosorbent assay.The expression of TLR4,NF-κB p65 and NLRP3 proteins in the CA1 region of the hippocampus was detected by immunohistochemistry.Results:After the drug intervention,compared with the blank control group,the model group exhibited higher systolic and diastolic pressures(P＜0.01).The escape latency and the first time of acrossing the platform were prolonged in model group,while the total time and distance of target quadrant were decreased in model group(P＜0.01).The ultrastructure of hippocampal synapses was blurred in model group,with some synaptic structures showing fusion,mitochondrial cristae swelling and rupture within synapses,a significant reduction in synaptic vesicles,and a smaller thickness of dense material after synapses(P＜0.01).The levels of IL-1β and IL-18 in hippocampal were increased in model group(P＜0.01).Additionally,the expression of TLR4,NF-κB p65 and NLRP3 proteins in hippocampal was upregulated in model group(P＜0.01 or P＜0.05).Compared with the model group,positive control group,GTJYJYF low-dose group and GTJYJYF medium-dose group exhibited lower systolic and diastolic pressures(P＜0.01 or P＜0.05).The escape latency and the first time of acrossing the platform were decreased,while the total time and distance of target quadrant were prolonged in positive control group,GTJYJYF low-dose group,GTJYJYF medium-dose group and GTJYJYF high-dose group.There was clear synaptic structures in GTJYJYF high-dose group,with the presence of presynaptic and postsynaptic membranes,an increase in synaptic vesicles in the presynaptic membrane,and an increase in the thickness of dense material after synapses(P＜0.01).The hippocampal levels of IL-1β and IL-18 were significantly reduced in positive control group,GTJYJYF medium-dose group and GTJYJYF high-dose group(P＜0.05).The expression of TLR4,NF-κB p65 and NLRP3 proteins was decreased in positive control group,GTJYJYF low-dose group,GTJYJYF medium-dose group and GTJYJYF high-dose group(P＜0.05).Conclusion:GTJYJYF can reduce blood pressure in hypertensive rats with complicated depression,improve learning and memory function,and alleviate the cognitive impairment The mechanism may be related to inhibit the expression of TLR4,NF-κB p65 and NLRP3 proteins,reduce the release of inflammatory factors and improve the hippocampal synaptic plasticity.
hypertension complicated with depressionGouteng Jiangya Jieyu Formulaultrastructure of hippocampal synapsestoll-like receptor 4NF-κBNLRP3learning and memory functionrat
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