Schisandrae Chinensis Fructus inhibits behavioral deficits induced by sleep deprivation and chronic unpredictable mild stress via increased signaling of brain‐derived neurotrophic factor

The present study was undertaken to explore the interactions between sleep deprivation (SD) and Schisandrae Chinensis Fructus (SCF) treatment in the antidepressant‐like effects. We observed that SD aggravated the anxiety‐like behavior induced by chronic unpredictable mild stress (CUMS) in the elevated plus maze test. However, the forced swimming test and sucrose preference test showed that SD (12 hr) alleviated the depressive symptoms and SD (72 hr) has the opposite effects. Administration of SCF showed a promising therapeutic effect on depression and anxiety induced by CUMS and SD. Moreover, SCF could potential strengthen the antidepressant‐like effects of SD (12 hr) according to the behavioral tests. In addition, the BDNF level in hippocampus was elevated by SD (12 hr) and SCF treatment and together with the upregulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling pathways. Besides, the protein levels of p70S6K and PSD95, which are downstream targets of mTOR, also increased by the treatment. These results indicated that the antidepressant‐like effect of SCF in the CUMS depends on the activation of BDNF and the modulation of TrkB/CREB/ERK and PI3K/AKT/GSK3β/mTOR signaling cascades, and SD (12 hr) shared a common etiology consisting of complex bidirectional interactions with SCF.     

Antidepressant‐like effects of 20(S)‐protopanaxadiol in a mouse model of chronic social defeat stress and the related mechanisms

20(S)‐Protopanaxadiol (PPD) is a basic aglycone of the dammarane triterpenoid saponins and exerts antidepressant‐like effects on behaviour in the forced swimming test (FST) and tail suspension test (TST) and in rat olfactory bulbectomy depression models. However, the antidepressant effects of PPD have not been studied thoroughly. The objective of the present study was first to investigate the effect of PPD on depression behaviours induced by chronic social defeat stress (CSDS) in mice. The results showed that CSDS was effective in producing depression‐like behaviours in mice, as indicated by decreased responses in the social interaction test, sucrose preference test, TST, and FST, and that this effect was accompanied by noticeable alterations in the levels of oxidative markers (superoxide dismutase, catalase, and lipid peroxidation) and monoamines (5‐HT and NE) in the hippocampus and serum corticosterone levels. Additionally, western blot analysis revealed that CSDS exposure significantly downregulated BDNF, p‐TrkB/TrkB, p‐Akt/Akt, and p‐mTOR/mTOR protein expression in the hippocampus. Remarkably, chronic PPD treatment significantly ameliorated these behavioral and biochemical alterations associated withCSDS‐induced depression. Our results suggest that PPD exerts antidepressant‐like effects in mice with CSDS‐induced depression and that this effect may be mediated by the normalization of neurotransmitter and corticosterone levels and the alleviation of oxidative stress, as well as the enhancement of the PI3K/Akt/mTOR‐mediated BDNF/TrkB pathway.     

基于雌激素受体通路探讨青娥丸对CUMS大鼠的抗抑郁机制

目的:研究青娥丸对慢性温和不可预知应激模型(CUMS)大鼠的抗抑郁效果,及其对雌激素受体及相关信号通路的调控作用,探讨青娥丸的抗抑郁机制。方法:54只SD大鼠建立CUMS抑郁大鼠模型,实验设为正常组、模型组、草酸依他普伦组(6.3 mg·kg^-1)及青娥丸低、中、高剂量组(1.71,5.13,15.39 g·kg^-1)。CUMS造模4周后给予各组相应药物治疗2周,采用行为学[糖水消耗实验(SPT),强迫游泳实验(FST),旷场实验(OFT)]评价大鼠抑郁状态;采用蛋白免疫印迹法(Western blot)检测雌激素受体α(ERα),雌激素受体β(ERβ),脑源性神经营养因子(BDNF)及酪氨酸激酶受体B(Trk B)的蛋白表达水平。结果:与正常组比较,模型组大鼠的糖水消耗率及旷场得分均下降(P<0.05,P<0.01),游泳不动时间显著延长(P<0.01),同时ERα,ERβ,BDNF和Trk B的蛋白表达水平下降(P<0.05,P<0.01);与模型组比较,各给药组大鼠的行为学表现得到改善,糖水消耗率及旷场得分增加(P<0.05,P<0.01),游泳不动时间减少(P<0.05),同时ERα,ERβ,BDNF和Trk B蛋白的表达明显上调(P<0.05,P<0.01),其中青娥丸中剂量组的调节作用更为显著。结论:青娥丸可改善CUMS模型大鼠的抑郁样行为,其机制可能与上调ERα,ERβ的表达,激活雌激素受体介导的ERβ/BDNF/Trk B通路起到神经保护作用有关。     

Retracted: Ganoderic acid A alleviates hypoxia‐induced apoptosis,autophagy, and inflammation in rat neural stem cells through the PI3K/AKT/mTOR pathways

Effects of ganoderic acid A (GAA), a lanostane triterpene, on hypoxia‐ischemia encephalopathy (HIE) remain unclear. We aimed to figure out the specific role of GAA in hypoxia‐treated neural stem cells (NSCs) as well as the regulatory mechanisms. Primary rat NSCs were incubated under hypoxia to simulate HIE. Viability and apoptosis of hypoxia‐injured NSCs were measured by cell counting kit‐8 and flow cytometry assays, respectively. Proteins related to apoptosis, autophagy, and the PI3K/AKT/mTOR pathways were evaluated by Western blot analysis. LY294002 and rapamycin were added to inhibit the PI3K/AKT pathway and mTOR pathway, respectively. Enzyme‐linked immunosorbent assay was carried out to test the release of proinflammatory cytokines. We found that hypoxia‐induced decrease of cell viability, increases of apoptotic cells and autophagy, and the release of IL‐6, IL‐1β, and TNF‐α were all attenuated by GAA stimulation. Activation of caspases induced by hypoxia was alleviated by GAA. Furthermore, we found that inhibition of the PI3K/AKT pathway eliminated the effects of GAA on apoptosis and proinflammatory cytokines release in hypoxia‐injured NSCs. Meanwhile, inhibition of the mTOR pathway abrogated the effects of GAA on cell autophagy in hypoxia‐injured NSCs. In conclusion, GAA alleviated hypoxia‐induced injury in NSCs might be through activating the PI3K/AKT and mTOR pathways.     

陈皮提取物改善慢性温和不可预知应激小鼠行为和海马BDNF的研究

目的:探讨陈皮提取物对慢性温和不可预知应激(CUMS)抑郁模型小鼠的行为和对脑源性神经营养因子(BDNF)表达水平的影响。方法:ICR小鼠根据糖水偏好百分比随机分为空白对照组、模型对照组、阳性对照盐酸氟西汀20 mg·kg-1组及陈皮提取物100,200,400 mg·kg-1组;除空白对照组外,各组均接受CUMS,造模28 d后开始灌胃给药;各组连续给药28 d后,糖水偏好实验测定糖水偏好百分比、新奇抑制摄食实验测定摄食潜伏期、强迫游泳实验测定不动时间;荧光实时定量PCR和ELISA法测定大脑海马BDNF含量。结果:慢性应激后,模型对照组小鼠糖水偏好百分比减少,摄食潜伏期延长,不动时间增多,海马BDNF含量显著降低;与模型对照组比较,陈皮提取物组能显著改善抑郁小鼠行为学指标,显著提高小鼠海马BDNF含量。结论:陈皮提取物对CUMS模型小鼠有抗抑郁作用,其机制可能与增加海马BDNF有关。     

Bushenhuoxue improves cognitive function and activates brain-derived neurotrophic factor-mediated signaling in a rat model of vascular dementia

OBJECTIVE: To explore the protective mechanisms of the Traditional Chinese Medicine Bushenhuoxue(BSHX) in a rat model of vascular dementia(VD).METHODS: A rat model of VD was developed using bilateral common carotid artery occlusion(BCCAO).Rats were administered BSHX(10.14 or 5.07 g/kg),nimodipine(11.06 mg/kg; positive control), or saline(control) by gavage daily for 30 d post-surgery.Learning and memory abilities were assessed using the Morris water maze. Morphological changes in the hippocampus were observed using light microscopy(hematoxylin and eosin staining) and transmission electron microscopy(TEM). The m RNA and protein expression levels of brain-derived neurotrophic factor(BDNF), tyrosine receptor kinase B(Trk B), phosphatidyl inositol 3-kinase(PI3 K), serine/threonine kinase(AKT), and c AMP response element binding protein(CREB) were measured by real-time polymerase chain reaction(RT-PCR) and Western blot, respectively.RESULTS: Compared with the sham group, rats with BCCAO exhibited impaired learning and memory abilities(Morris water maze) and showed abnormalities in neuronal morphology(light microscopy)and ultrastructure(TEM) in the hippocampus. They also had decreased m RNA and protein expressions of BDNF, Trk B, PI3 K, AKT, and CREB in hippocampal tissue(all P 0.05). In rats with BCCAO, administration of BSHX attenuated deficits in learning and memory, improved the morphology and ultrastructure of hippocampal neurons, and enhanced m RNA and protein expression levels of BDNF, Trk B, PI3 K,AKT, and CREB(all P 0.05).CONCLUSION: BSHX may protect hippocampal neurons and improve learning and memory abilities, at least in part via the activation of BDNF/Trk B/PI3 K/AKT/CREB signaling.     

基于慢性轻度不可预知性温和型应激的C57BL/6N小鼠抑郁模型的建立与评价

目的：探索慢性轻度不可预知性温和型应激(CUMS)法建立抑郁症C57BL/6N小鼠模型的条件,观察不同时点该模型行为学变化,对该模型进行评价和优化。方法：对C57BL/6N小鼠进行连续8周的CUMS应激来诱导其抑郁状态。分别在造模3、5、8周时通过糖水偏好实验(SPT)、旷场实验(OFT)、强迫游泳实验(FST)、悬尾实验(TST)等行为学实验,观察小鼠抑郁样行为的改变。结果：与对照组相比,发现各时点CUMS组小鼠一般状态均较差,出现毛发脱落、体型瘦小、活动减少等;造模3、5、8周时均出现糖水偏好率下降,FST和TST不动时间的延长,OFT垂直运动次数减少等,提示CUMS组小鼠出现快感缺失、绝望感及探索能力下降;造模8周时出现OFT水平运动总路程缩短、运动速度减慢,提示CUMS组小鼠出现了自发运动能力下降。结论：CUMS应激可以成功建立C57BL/6N小鼠抑郁模型,并且随着应激时间的延长,C57BL/6N小鼠的抑郁表现逐渐加重。     

逍遥散对抑郁大鼠海马CA1区PI3K/AKT信号通路的调节作用研究

目的:本研究旨在探讨逍遥散通过调节PI3K/Akt信号通路进而改善由谷氨酸引起的兴奋性损伤的机制。方法:100只雄性SD大鼠随机分为正常组、模型组、逍遥散组和氟西汀组,利用CUMS方法造模成为抑郁模型大鼠,上述组别分别予以双蒸水、双蒸水、逍遥散药液、氟西汀溶液连续灌胃3周,后进行行为学观察及相关指标检测。采用旷场试验(OFT)和蔗糖偏好试验(SPT)评价逍遥散的抗抑郁作用;ELISA法测定海马组织中5-HT、NE水平;比色法检测各组大鼠海马CA1区谷氨酸水平;RT-qPCR检测海马CA1区NR2B、PI3K的mRNA水平;western blot检测海马CA1区NR2B、PI3K、P-AKT、Akt的蛋白表达。结果:逍遥散的体内干预可显著提高抑郁模型大鼠海马组织中的5-HT、NE水平、降低海马CA1区谷氨酸水平、增加了海马CA1区NR2B、PI3K及P-AKT/Akt比值,显著改善了大鼠的抑郁症状。结论:逍遥散可显著改善经慢性应激刺激后大鼠的抑郁样行为,其机制可能与降低谷氨酸兴奋性毒性,从而提高PI3K/Akt信号通路活性有关。     

6-Methoxydihydrosanguinarine induces apoptosis and autophagy in breast cancer MCF-7 cells by accumulating ROS to suppress the PI3K/AKT/mTOR signaling pathway

6-Methoxydihydrosanguinarine (6-MDS) is a natural benzophenanthridine alkaloid extracted from Hylomecon japonica (Thunb.) Prantl. It is the first time to explore the effect and mechanism of 6-MDS in breast cancer. Network pharmacology, molecular docking, and molecular dynamics simulation technology were adopted to identify the potential targets and pathways of 6-MDS in breast cancer. Besides, cell proliferation, apoptosis, and western blotting assays were conducted to investigate the effect of 6-MDS on MCF-7 cells. Network pharmacology, molecular docking, and molecular dynamics simulation results confirmed the effect of 6-MDS on resisting breast cancer via the PI3K/AKT/mTOR signaling pathway. In addition, the functional experiments results demonstrated that 6-MDS inhibited proliferation and induced apoptosis and autophagy. The autophagy inhibitor chloroquine and the silence of Atg5 augmented the effect of 6-MDS on promoting apoptosis. Furthermore, 6-MDS suppressed the PI3K/AKT/mTOR signaling pathway, and the PI3K inhibitor LY294002 enhanced these changes and promoted the 6-MDS pro-apoptotic and autophagy effects. 6-MDS triggered the generation of reactive oxygen species. The pretreatment with antioxidant N-acetyl-L-cysteine reversed the changes induced by 6-MDS, including increases in apoptosis and autophagy and inhibition of the PI3K/AKT/mTOR pathway. In conclusion, 6-MDS induces the apoptosis and autophagy of MCF-7 cells by ROS accumulation to suppress the PI3K/AKT/mTOR signaling pathway.     

Rapid antidepressant‐like effect of Fructus Aurantii depends on cAMP‐response element binding protein/Brain‐derived neurotrophic facto by mediating synaptic transmission

Several studies reported the relative antidepressant effects of Fructus Aurantii (FRA) with repeated treatment, the rapid antidepressant effects of FRA and the underlying mechanisms remained unclear. We, therefore, examined the rapid antidepressant actions of FRA in behavioral tests in mice and tested the underlying molecular mechanisms. We found FRA, like ketamine, reversed the behavioral deficits both in lipopolysaccharide(LPS)‐induced and learned helplessness (LH) models at 1 day after a single administration. FRA was also capable of increasing the expressions of protein kinase A/cAMP‐response element‐binding protein/brain‐derived neurotrophic factor (PKA/CREB/BDNF) signaling in hippocampus. Consistent with ketamine, FRA up‐regulated the expressions of GABAergic receptor (GAD67) and glutamatergic receptor 1 (GluR1) in mouse hippocampus both exposed to LPS and LH. Moreover, synaptic proteins such as postsynaptic density‐95 (PSD95) and synapsin1 were also up‐regulated by a single dose of FRA both in LH and LPS models, like ketamine. Finally, metadoxine (an antagonist of CREB) inhibited the antidepressant effects of FRA in tail suspension test (TST) and forced swimming test (FST) in LPS‐induced mice, which also blocked the phosphorylation of CREB and the expressions of neurotransmitters and synaptic molecules. Therefore, FRA had rapid antidepressant effects, which depended on PKA/CREB/BDNF pathway, subsequently regulated the downstream synaptic transmission.     

Antidepressant-like effect of the ethanolic extract from Suanzaorenhehuan Formula in mice models of depression

Ethnopharmacological relevance

Suanzaorenhehuan Formula (SHF) is a Chinese herbal formula for the treatment of depression-like disorders. It contains four herbs: Semen Ziziphi spinosae, Cortex Albiziae, Radix Paeoniae Alba and Semen Platycladi. The present study is to investigate the antidepressant-like effect of the ethanolic extract of SHF and its possible mechanisms.

Materials and methods

Mouse models of depression including the tail suspension test (TST), forced swimming test (FST) and chronic unpredicted mild stress (CUMS) were used to evaluate the effects of SHF extract. The mechanisms were examined by measuring monoamine neurotransmitters in mice hippocampus and frontal cortex, testing monoamine oxidase enzyme (MAO) activities in brain of CUMS-exposed mice.

Results

After one-week treatment, SHF extract (50, 100 and 200 mg/kg) induced a significant decrease on immobility time in TST. After two-week treatment, SHF extract (50, 100 and 200 mg/kg) led to a reduction in the immobility period in TST and FST. The 5-HT levels in mice hippocampus were increased only after 200 mg/kg SHF extract treatment. The noradrenaline (NE) levels were increased after 200 mg/kg SHF extract treatment in mice hippocampus and frontal cortex. SHF extract (50, 100 and 200 mg/kg) significantly inhibited monoamine oxidase-A (MAO-A) and monoamine oxidase-B (MAO-B) after 21-day CUMS exposure.

Conclusion

These findings demonstrated that ethanolic SHF extract produced an antidepressant-like effect and the mechanism of action involves the serotonergic, noradrenergic and monoamine oxidase enzyme systems although underlying mechanism still remains to be further elucidated.     

代谢组学研究复方柴归方超临界CO2提取物抗抑郁作用及其机制

采用小鼠悬尾试验（TST）、强迫游泳试验（FST）以及大鼠慢性温和不可预知应激（CUMS）模型评价复方柴归方超临界CO₂提取物（FFCGF）的抗抑郁作用;采用核磁共振代谢组学的方法,结合多元统计分析技术探讨FFCGF的抗抑郁作用机制。大鼠进行为期28 d的CUMS程序造模,药物干预28 d,与CUMS造模同时进行,造模过程中观察大鼠体重、糖水偏爱、穿越格数和直立次数的变化,造模结束后收集大鼠尿液,应用¹H-NMR技术结合多元统计分析方法分析大鼠尿液内源性代谢产物的变化规律,寻找潜在的生物标志物。结果显示FFCGF能明显减少小鼠悬尾试验和强迫游泳试验的不动时间,改善CUMS模型大鼠的体重、糖水偏爱、穿越格数和直立次数,说明FFCGF具有明确的抗抑郁作用。代谢组学结果显示空白组和模型组能明显区分,CUMS模型大鼠尿液中甘氨酸和丙酮酸含量显著升高,醋酸、琥珀酸、2-氧化戊二酸和柠檬酸含量显著降低（P < 0.05,0.01）,FFCGF能够明显调节CUMS程序引起的6种生物标志物的含量变化,使其恢复正常。FFCGF可能通过调节能量代谢、脂质代谢和氨基酸代谢发挥抗抑郁作用。     

人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响

目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间明显增加,表明慢性应激导致大鼠产生抑郁样行为.同时,抑郁大鼠的血清COR水平增加,海马GR、海马及皮层BDNF的mRNA表达水平均明显降低.给予人参皂苷(12.5,25,50 mg·kg-1)6周后,发现其能显著改善由慢性应激所致的大鼠抑郁行为及生化指标.各个组间海马MR的mRNA表达水平没有显著差异.结论:人参皂苷的抗抑郁作用机制可能通过调节下丘脑-垂体-肾上腺轴功能,进而提高脑组织BDNF 表达水平.     

中药抗肿瘤血管生成的信号通路研究

血管生成是肿瘤发生和转移的基本条件。调控肿瘤血管生成相关的信号通路包括PI3K/Akt/mTOR、Ras/Raf/MEK/ERK、Notch转导通路等。中药抗肿瘤血管生成的信号通路研究越来越受关注。调控PI3K/Akt/mTOR通路的中药多集中于抑制Akt的磷酸化,且清热药居多。调控Ras/Raf/MEK/ERK通路的中药多集中于抑制ERK的磷酸化,且活血化瘀药居多。调控Notch转导通路的中药多集中于抑制Notch1的表达,对配体的表达不一。对中药抗肿瘤血管生成的信号通路进行综述,旨在寻求新的血管生成抑制剂,阐明作用靶点,为肿瘤研究提供方向。     

[6]‐Gingerol enhances the cisplatin sensitivity of gastric cancer cells through inhibition of proliferation and invasion via PI3K/AKT signaling pathway

Cisplatin‐based chemotherapy is a widely used chemotherapeutic regimen for gastric cancer; however, drug resistance limits its efficacy. [6]‐Gingerol has been found to exhibit anticancer effects. Here, we aim to explore the potential of [6]‐gingerol in combination with cisplatin as a new regimen for gastric cancer. CCK‐8 assay and colony formation assay were used to determine the effect of [6]‐gingerol in combination with cisplatin on cell viability of gastric cancer cells. Flow cytometry was performed to assess cell cycle distribution. Wound‐healing assay and transwell invasion assay were conducted to examine the migration and invasion abilities. Cell cycle and invasion‐related proteins and mRNAs, as well as PI3K/AKT signaling proteins, were assessed by western blotting and quantitative real‐time polymerase chain reaction. Combination of [6]‐gingerol with cisplatin inhibited cell viability and enhanced cell cycle arrest at G1 phase compared with cisplatin alone. The combination treatment inhibited cell migration and invasion ability and decreased cyclin D1, cyclin A2, matrix metalloproteinase‐9, p‐PI3K, AKT, and p‐AKT protein expressions and increased P21 and P27 mRNA levels. Our study demonstrates that [6]‐gingerol enhances the cisplatin sensitivity of gastric cancer cells and that the mechanisms involve G1 phase arrest, migration and invasion suppression via PI3K/AKT signaling pathway.     

六味地黄汤干预抑郁大鼠学习记忆的作用机制

目的:探讨六味地黄汤对慢性抑郁大鼠记忆障碍的改善作用,并探讨其可能的作用机制。方法:Wistar雌性大鼠随机分为正常组(生理盐水)、慢性不可预见性温和应激(CUMS)模型组(生理盐水)、六味地黄汤低、中、高剂量组(2. 60,7. 81,23. 50 g·kg~(-1)·d~(-1))。除正常组外,其余各组造成CUMS模型。每周称体质量,观察其行为学指标变化;实时荧光定量聚合酶链式反应(Real-time PCR)检测其海马G蛋白偶联雌激素受体(GPR30),胞内磷脂酰肌醇激酶(PI3K),环磷酸腺苷反应元件结合蛋白(CREB),脑源性神经营养因子(BDNF) mRNA的表达;酶联免疫吸附测定(ELISA)检测血清中雌激素含量。结果:与正常组比较,模型组体质量、活动能力、兴趣等明显降低(P 0. 05,P 0. 01);与模型组比较,六味地黄汤2. 60,7. 81,23. 50 g·kg~(-1)可明显提高CUMS大鼠糖水偏好度(P 0. 01)和旷场实验的站立次数(P 0. 01);7. 81,23. 50 g·kg~(-1)明显提高旷场实验的总距离(P 0. 05,P 0. 01);2. 60,7. 81 g·kg~(-1)可缩短水迷宫实验寻台潜伏期(P 0. 01);7. 81 g·kg~(-1)可增加血清中雌激素含量(P 0. 05);CUMS模型组大鼠海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达明显下降(P 0. 05,P 0. 01),六味地黄汤2. 60 g·kg~(-1)显著增加海马组织内的GPR30,CREB mRNA表达(P 0. 05,P 0. 01),7. 81 g·kg~(-1)明显增加海马组织内的GPR30,PI3K,CREB,BDNF mRNA表达量(P 0. 05,P 0. 01)。结论:六味地黄汤具有抗抑郁作用,逆转CUMS大鼠抑郁样行为及学习记忆障碍,其中中剂量组药效最显著。其作用机制可能与增加血清中雌激素和提高大鼠海马GPR30,PI3K,CREB,BDNF mRNA表达有关。     

逍遥散对CUMS大鼠海马CA1区PI3K/AKT信号通路的调节作用研究

目的：本研究旨在探讨逍遥散通过调节PI3K/AKT信号通路进而改善由谷氨酸引起的兴奋性损伤的机制。 方法：100只雄性SD大鼠随机分为正常组、模型组、逍遥散组和氟西汀组,利用CUMS方法造模成为抑郁模型大鼠,上述组别分别予以双蒸水、双蒸水、逍遥散药液、氟西汀溶液连续灌胃3周,后进行行为学观察及相关指标检测。采用旷场试验(OFT)和蔗糖偏好试验(SPT)评价逍遥散的抗抑郁作用;ELISA法测定海马组织中5-HT、NE水平;比色法检测各组大鼠海马CA1区谷氨酸水平; RT-qPCR检测海马CA1区NR2B、PI3K的mRNA水平;western blot检测海马CA1区NR2B、PI3K、P-AKT、Akt的蛋白表达。 结果：逍遥散的体内干预可显著提高抑郁大鼠海马组织中的5-HT、NE水平、降低海马CA1区谷氨酸水平、增加了海马CA1区NR2B、PI3K及P-AKT/AKT比值,显著改善了大鼠的抑郁症状。 结论:逍遥散可显著改善经慢性应激刺激后大鼠的抑郁样行为,其机制可能与降低谷氨酸兴奋性毒性,从而提高PI3K/Akt信号通路活性有关。     

民族药铁包金基于FGF2/FGFR1通路改善抑郁样行为的作用机制研究※

目的 观察民族药铁包金对脂多糖（LPS）诱导的抑郁样行为的干预作用,并探讨其基于FGF2/FGFR1信号通路的分子作用机制。方法 将150只SPF级雄性小鼠随机分成3批,每批分成5组,即模型组、铁包金低剂组（2 g/kg）、铁包金中剂组（4 g/kg）、铁包金高剂组（8 g/kg）、氟西汀组（20 mg/kg）,各组给药1 h后分别进行强迫游泳实验（FST）、悬尾实验（TST）及开场实验（OFT）。另取60只SPF级雄性小鼠随机分成6组,即正常对照组、模型对照组、铁包金低剂组（2 g/kg）、铁包金中剂组（4 g/kg）、铁包金高剂组（8 g/kg）、氟西汀组（20 mg/kg）,各组持续给予相应药物7 d,最后一次给药后注射LPS,采用糖水偏好实验和FST评价动物抑郁样行为。采用Western Blot方法测小鼠海马组织中成纤维细胞生长因子2（FGF2）、磷酸化及总成纤维细胞生长因子受体1（FGFR1）的含量。结果 铁包金可以缩短小鼠强迫游泳和悬尾不动时间,对小鼠自发活性行为则没有影响,提示铁包金具有良好的抗抑郁效果。同时,铁包金能够显著增加LPS抑郁小鼠糖水偏好值,减少小鼠游泳不动时间;并可显著增加小鼠大脑海马FGF2表达量,提高FGFR1磷酸化水平。结论 铁包金具有抗抑郁作用,其作用机制与激活大脑海马FGF2/FGFR1信号通路相关。     

嗅三针对蛛网膜下腔出血并发认知障碍大鼠海马神经元及Caspase-3表达的影响

目的:研究嗅三针对蛛网膜下腔出血并发认知障碍模型大鼠的干预作用及对海马神经元Caspase-3、PI3K、AKT mRNA和蛋白表达的影响。方法:取清洁级雄性SD大鼠60只,随机分为空白组、模型组、嗅三针组、尼莫地平组以及假针刺组,每组12只。各组大鼠干预后,采用荧光定量PCR检测大鼠海马区Caspase-3、PI3K、AKT mRNA表达,Western blot技术检测Caspase-3、PI3K、AKT蛋白表达量。结果:与模型组比较,嗅三针组和尼莫地平组海马中PI3K、AKT mRNA表达量均有不同程度升高,且嗅三针组高于尼莫地平组,差异有统计学意义(均P<0.05),嗅三针组和尼莫地平组Caspase-3 mRNA表达均低,差异有统计学意义(均P<0.05)。与模型组比较,尼莫地平组及嗅三针组PI3K、AKT蛋白的表达均升高,Caspase-3蛋白表达降低,差异有统计学意义(均P<0.05)。结论:嗅三针对蛛网膜下腔出血并发认知障碍大鼠的神经保护作用机制可能是通过激活大鼠脑组织的PI3K/AKT信号通路,抑制Caspase-3蛋白表达及细胞凋亡,减轻神经组织炎性损伤。     

乌索酸调节PI3K/AKT/mTOR信号通路在结直肠癌中的研究进展

乌索酸（Ursolic acid,UA）是一种广泛存在于植物的草、叶、花和果实中的具有抗氧化,抗菌,抗炎,肝保护,免疫调节,抗肿瘤,化学预防,心脏保护、抗高脂血症和降低血糖等活性的五环三萜类化合物。本文综述了乌索酸结构与抗肿瘤机制、PI3K/AKT/mTOR信号通路参与结直肠癌进程以及乌索酸调节PI3K/AKT信号通路阻碍结直肠癌进展。