巴戟天水提物对慢性应激诱导的大鼠抑郁样行为的改善作用和机制研究OACSTPCD
Effects and mechanisms of an aqueous extract of Morinda officinalis How on chronic stress-induced depression-like behavior in rats
目的 探究巴戟天水提物的抗抑郁效果及作用机制.方法 SD大鼠36只,随机分成空白组、模型组、阳性药盐酸氟西汀组、巴戟天水提物低、中、高3个剂量组.采用慢性不可预知性应激方法造模并给药28 d,通过行为学评价巴戟天水提物的抗抑郁效果,苏木精-伊红染色法(HE)观察大鼠海马神经细胞的形态,免疫组化检测核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体和小胶质细胞活化标志物离子化钙结合适配分子1(Iba-1)的表达水平,Western印迹检测脑源性神经营养因子(BDNF)、磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(Akt)、糖原合酶激酶3β(GSK3β)蛋白表达水平.结果 给药组较模型组糖水偏好率明显增加(P<0.01),强迫游泳的不动时间显著缩短(P<0.05);大鼠海马CA3区神经元形态有所改善;NLRP3炎症小体和小胶质细胞Iba-1蛋白表达减少;BDNF、PI3K及其磷酸化(p-PI3K)蛋白、Akt及其磷酸化(p-Akt)蛋白表达增加,GSK3β及其磷酸化(p-GSK3β)蛋白表达减少.结论 巴戟天水提物可改善慢性刺激诱导的大鼠抑郁样行为,其作用机制可能是通过改善神经元形态、抑制海马炎症反应、调控BDNF/PI3K/Akt/GSK3β通路途径实现的.
Objective To explore the antidepressant effect and mechanism of an aqueous extract of Morinda officinalis How.Methods Thirty-six SD rats were randomly assigned to the control group,model group,the fluoxetine hydrochloride group and low,medium,and high dose groups of aqueous extract of Morinda officinalis How.A chronic unpredictable stress method was used to create a model which was administered for 28 days.Behavioral analysis was conducted to evaluate the antidepressant effect of the aqueous extract of Morinda officinalis How.Hematoxylin-eosin staining was used to observe the morphology of hippocampal neurons in rats while immunohistochemistry staining was adopted to detect the expression levels of inflammasome NLRP3 and microglial marker protein Iba-1.Western blotting was used to detect the expression levels of BDNF,PI3K,Akt,and GSK3β.Results After medication,the behavior and physiology of depressed rats were significantly improved.The Sugar-water preference ratio was significantly increased(P<0.01)and the forced swimming immobility time was significantly shortened(P<0.05).The morphology of neurons in the CA3 area of the rat hippocampus was improved.The protein expressions of NLRP3 and Iba-1 were reduced.The expression levels of BDNF,PI3K,p-PI3K,Akt,and p-Akt proteins were up-regulated while the those of GSK3β and p-GSK3β proteins were down-regulated.Conclusion The aqueous extract of Morinda officinalis How can improve the depression-like behavior induced by chronic stimulation in rats,and its antidepressant mechanism may be related to improving neuronal morphology,inhibiting hippocampal inflammatory response and regulating BDNF/PI3K/Akt/GSK3β pathway.
刘晗静;李硕;王碧坤;王增明;张善柠;刘圆圆;赵春颖;郑爱萍
承德医学院,河北承德 067000解放军总医院京南医疗区,北京 100850军事科学院军事医学研究院毒物药物研究所,北京 100850
中医学
巴戟天水提物大鼠慢性不可预知性温和刺激抗抑郁炎症反应
aqueous extract of Morinda officinalis Howratchronic unpredictable mild stimulationantidepressantsinflammation
《军事医学》 2024 (003)
195-201 / 7
国家科技创新2030重大项目(2021ZD0202003)
评论