黄芩苷通过上调SIRT1保护SH-SY_5Y氧化应激的损伤

观察黄芩苷(baicalin,BL)对过氧化氢诱导SH-SY5Y细胞损伤的作用,并初步探讨SIRT1是否是其发挥作用的靶点及其可能机制。培养的人神经母细胞瘤细胞系SH-SY5Y细胞加入黄芩苷(25、50及100μmol·L-1)预孵育12 h,加入H2O2(150μmol·L-1)作用24 h诱导产生氧化损伤,应用MTT比色法检测细胞存活率,测定培养液中乳酸脱氢酶(LDH)漏出率、一氧化氮(NO)含量;并采用流式细胞仪检测细胞凋亡及应用免疫荧光组化法检测Caspase-3的活性、RT-PCR检测SIRT1水平。结果表明,与H2O2模型组比较,黄芩苷(50和100μmol·L-1)组的细胞存活率增高(P<0.05、P<0.01),而LDH、NO的释放量及细胞凋亡数(P<0.05、P<0.01)、Caspase-3的表达量均减少;SIRT1 mRNA表达明显(P<0.05、P<0.01)。黄芩苷对H2O2损伤的SY5Y细胞具有保护作用,可减轻神经细胞的损伤、抑制细胞的凋亡,其作用机制可能是通过上调SIRT1水平而抑制Caspase-3表达实现的。     

Activation of ERK1/2, JNK and PKB by hydrogen peroxide in human SH-SY5Y neuroblastoma cells: role of ERK1/2 in H2O2-induced cell death

Reactive oxygen species including H(2)O(2) activate an array of intracellular signalling cascades that are closely associated with cell death and cell survival pathways. The human neuroblastoma SH-SY5Y cell line is widely used as model cell system for studying neuronal cell death induced by oxidative stress. However, at present very little is known about the signalling pathways activated by H(2)O(2) in SH-SY5Y cells. Therefore, in this study we have investigated the effect of H(2)O(2) on extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase B (PKB) activation in undifferentiated and differentiated SH-SY5Y cells. H(2)O(2) stimulated time and concentration increases in ERK1/2, JNK and PKB phosphorylation in undifferentiated and differentiated SH-SY5Y cells. No increases in p38 MAPK phosphorylation were observed following H(2)O(2) treatment. The phosphatidylinositol 3-kinase (PI-3K) inhibitors wortmannin and LY 294002 ((2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) inhibited H(2)O(2)-induced increases in ERK1/2 and PKB phosphorylation. Furthermore, H(2)O(2)-mediated increases in ERK1/2 activation were sensitive to the MAPK kinase 1 (MEK1) inhibitor PD 98059 (2'-amino-3'-methoxyflavone), whereas JNK responses were blocked by the JNK inhibitor SP 600125 (anthra[1-9-cd]pyrazol-6(2H)-one). Treatment of SH-SY5Y cells with H(2)O(2) (1 mM; 16 h) significantly increased the release of lactate dehydrogenase (LDH) into the culture medium indicative of a decrease in cell viability. Pre-treatment with wortmannin, SP 600125 or SB 203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole; p38 MAPK inhibitor) had no effect on H(2)O(2)-induced LDH release from undifferentiated or differentiated SH-SY5Y cells. In contrast, PD 98059 and LY 294002 significantly decreased H(2)O(2)-induced cell death in both undifferentiated and differentiated SH-SY5Y cells. In conclusion, we have shown that H(2)O(2) stimulates robust increases in ERK1/2, JNK and PKB in undifferentiated and differentiated SH-SY5Y cells. Furthermore, the data presented clearly suggest that inhibition of the ERK1/2 pathway protects SH-SY5Y cells from H(2)O(2)-induced cell death.     

Novel squamosamide derivative （compound FLZ） attenuates Aβ25-35^- induced toxicity in SH-SY5Y cells

AIM: The aim of the present study was to investigate the protective effect of compound N-[2-(4-hydroxy-phenyl)-ethyl]-2-(2,5-dimethoxy-phenyl)-3-(3-methoxy-4-hydroxy-phenyl)-acrylamide (compound FLZ), a novel synthetic analogue of nature squamosamide, on Abeta25-35-induced toxicity and its active mechanism in human neuroblastoma SH-SY5Y cells. METHODS: SH-SY5Y cells were pre-incubated with various concentrations of compound FLZ for 30 min and then cultivated with Abeta25-35 (25 micromol/L) for 48 h to induce neurotoxicity. Cell viability, lactate dehydrogenase (LDH) release, and the glutathione (GSH) level were determined by a biochemical analysis. The cell apoptotic ratio and intracellular reactive oxygen species (ROS) level were measured by a flow cytometry analysis. The expression of apoptosis protein (Bcl-2 and Bax) and cytochrome c release were assayed by the Western blot method. RESULTS: The pretreatment of SH-SY5Y cells with FLZ (1 and 10 micromol/L) markedly increased cell viability and decreased LDH release and morphological injury. Also, FLZ attenuated the Abeta25-35-induced apoptotic cell ratio, regulated the apoptosis protein (Bcl-2 and Bax) expression, and decreased the cytochrome c release from mitochondria. FLZ also significantly inhibited the generation of ROS and the depletion of GSH induced by Abeta25-35 in SH-SY5Y cells. CONCLUSION: FLZ has protective action against Abeta25-35-induced toxicity in SH-SY5Y cells, which might be mediated through its antioxidant property.     

黄芩苷对H_2O_2诱导的SH-SY5Y细胞损伤的保护作用及其对Trx表达的影响

目的探讨黄芩苷对H2O2诱导的SH-SY5Y细胞损伤的保护作用及其作用机制。方法采用体外培养细胞的方法,建立SH-SY5Y细胞H2O2损伤模型。分设药物组(50,100,200μmol/L)、H2O2损伤组、阴性对照组。采用MTT法检测细胞活力,采用实时荧光定量PCR法检测各组细胞的Trx表达的变化。结果同H2O2损伤组比较,黄芩苷能明显减轻H2O2引起的SH-SY5Y细胞的损伤,同时Trx表达升高。结论黄芩苷对H2O2诱导的SH-SY5Y细胞损伤具有明显的保护作用,其作用机制可能是黄芩苷通过上调Trx表达,起到抗氧化作用,继而起到抗凋亡的作用。     

A novel mechanism for pergolide-induced neuroprotection: inhibition of NF-kappaB nuclear translocation

We previously demonstrated that the dopaminergic agonist pergolide, independently from its DA agonist activity, can exert neuroprotective effects against cell death induced in SH-SY5Y neural cells by H(2)O(2) treatment. Since oxidative stress in SH-SY5Y neural cells is known to activate the NF-kappaB pathway we tested the hypothesis that pergolide may interfere with NF-kappaB activity. Based on Western blot analysis and immunocytochemistry, pergolide was found to prevent H(2)O(2)-induced apoptosis by inhibiting NF-kappaB nuclear translocation and activation of p53 signalling pathway. Similarly, the cell-permeable SN50 peptide, which is known to block NF-kappaB nuclear translocation, prevented both H(2)O(2)-induced p53 expression and apoptosis. The mechanism of action of pergolide responsible for neuroprotection differed from that of antioxidants. In fact, Vitamin E, contrary to pergolide and SN50, rescued neuronal cells from H(2)O(2)-induced apoptosis acting upstream NF-kappaB activation, as demonstrated by the prevention of H(2)O(2)-induced IkappaB degradation. These data suggest a novel site of action of pergolide that may account for additional pharmacological properties of this drug.     

莫诺苷抑制过氧化氢诱导的神经细胞损伤作用

目的研究从中药山茱萸提取的有效成分莫诺苷抑制过氧化氢(H2O2)诱导的神经细胞氧化损伤作用。方法培养的人神经母细胞瘤细胞系SH-SY5Y细胞加入莫诺苷1、10、100μmol/L预孵育24h,加入H2O2300μmol/L作用18h诱导产生氧化损伤,测定细胞内细胞色素C及脑源性神经生长因子(BDNF)的含量。结果莫诺苷1、10、100μmol/L使细胞色素C的释放显著降低18%(P<0.05)、28%(P<0.05)、35%(P<0.01);BDNF(10、100mol/L)的释放增加(P<0.01)。结论莫诺苷的神经保护作用是通过抑制细胞色素C的释放,抑制神经细胞凋亡,并能促进神经细胞增加神经营养因子的释放,进而促进神经细胞的再生,抑制神经细胞氧化损伤。     

Mechanisms of chromium (VI)-induced apoptosis in anterior pituitary cells

In this study, we investigated the protective effects of rosmarinic acid (RA) on H(2)O(2)-induced neurotoxicity in human dopaminergic cell line, SH-SY5Y. Results showed that RA significantly attenuated H(2)O(2)-induced reactive oxygen species (ROS) generation and apoptotic cell death. Rosmarinic acid effectively suppressed the up-regulation of Bax and down-regulation of Bcl-2. Furthermore, RA stimulated the antioxidant enzyme heme oxygenase-1 (HO-1). We also demonstrated that the HO-1 induction by RA was associated with the protein kinase A (PKA) and phosphatidylinositiol-3-kinase (PI3K) signaling pathways. These results suggest that RA can protect SH-SY5Y cells under oxidative stress conditions by regulating apoptotic process. Thus, RA should be clinically evaluated for the prevention of neurodegenerative diseases.     

黄芩苷对SH-SY5Y细胞损伤的Bcl-2和Bcl-xL mRNA基因表达的影响

目的 探讨黄芩苷对过氧化氢(H₂O₂)诱导的SH-SY5Y细胞损伤的Bcl-2和Bcl-xL mRNA表达的影响. 方法 建立人神经母细胞瘤SH-SY5Y细胞的体外H₂O₂损伤模型,采用噻唑蓝(MTT)法检测不同浓度黄芩苷对SH-SY5Y细胞存活率的影响,采用Real-time PCR法检测各组细胞的Bcl-2和Bcl-xL表达水平的变化. 结果 50,100,200 μmol.L^-1黄芩苷组细胞存活率分别为130.4%,89.9%和60.9%,H₂O₂损伤组细胞存活率为33.9%,50,100 μmol.L^-1黄芩苷组与H₂O₂损伤组比较,差异有统计学意义(P<0.01). 50,100,200 μmol.L^-1黄芩苷组Bcl-2 mRNA表达量分别为(11.48±0.48),(7.37±1.57),(7.39±2.01),H₂O₂损伤组为(5.84±0.58);50,100,200 μmol.L-1黄芩苷组Bcl-xL mRNA表达量分别为(19.96±2.22),(11.36±3.94),(13.07±2.37),H₂O₂损伤组为(7.95±0.58),50 μmol.L^-1组Bcl-2 和Bcl-xL mRNA与H^₂O^₂损伤组比较,差异均有统计学意义(均P<0.05). 结论 黄芩苷对H₂O₂诱导的SH-SY5Y细胞损伤的保护作用,可能与黄芩苷上调Bcl-2和Bcl-xL的表达而起到抗凋亡的作用有关.     

Synergistic effects of hydrogen peroxide and ethanol on cell viability loss in PC12 cells by increase in mitochondrial permeability transition

The promoting effect of ethanol against the cytotoxicity of hydrogen peroxide (H2O2) in differentiated PC12 cells was assessed by measuring the effect on the mitochondrial membrane permeability. Treatment of PC12 cells with H2O2 resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. In PC12 cells and dopaminergic neuroblastoma SH-SY5Y cells, the promoting effect of ethanol on the H2O2-induced cell death was increased with exposure time. Ethanol promoted the nuclear damage, change in the mitochondrial membrane permeability, ROS formation and decrease in GSH contents due to H2O2 in PC12 cells. Catalase, carboxy-PTIO, Mn-TBAP, N-acetylcysteine, cyclosporin A and trifluoperazine inhibited the H2O2 and ethanol-induced mitochondrial dysfunction and cell injury. The results show that the ethanol treatment promotes the cytotoxicity of H2O2 against PC12 cells. Ethanol may enhance the H2O2-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c and subsequent activation of caspase-3, which is associated with the increased formation of ROS and depletion of GSH. The findings suggest that ethanol as a promoting agent for the formation of mitochondrial permeability transition may enhance the neuronal cell injury caused by oxidants.     

20-羟基蜕皮甾酮对H_2O_2诱导SH-SY5Y细胞损伤的保护作用

本文旨在研究一种类固醇激素即20-羟基蜕皮甾酮对H2O2诱导的SH-SY5Y细胞损伤的保护作用及其作用机制。预孵育20-羟基蜕皮甾酮可以明显提高H2O2诱导的SH-SY5Y细胞的生存率,减少乳酸脱氢酶（LDH）漏出率,抑制脂质过氧化水平（MDA）升高,提高超氧化物歧化酶（SOD）活性。此外,20-羟基蜕皮甾酮可以通过降低Bax/Bcl-2的比值,延缓caspase-3的活化来抑制H2O2诱导的细胞凋亡。本研究表明20-羟基蜕皮甾酮对H2O2诱导的SH-SY5Y细胞具有保护作用,有可能用于由氧化应激和凋亡导致的神经退行性疾病的治疗。     

Cytoprotection by lithium and valproate varies between cell types and cellular stresses

Despite much evidence that lithium and valproate, two commonly used mood stabilizers, exhibit neuroprotective properties against an array of insults, the pharmacological relevance of such effects is not clear because most of these studies examined the acute effect of these drugs in supratherapeutic doses against insults which were of limited disease relevance to bipolar disorder. In the present study, we investigated whether lithium and valproate, at clinically relevant doses, protects human neuroblastoma (SH-SY5Y) and glioma (SVG and U87) cells against oxidative stress and endoplasmic reticulum stress in a time-dependent manner. Pretreatment of SH-SY5Y cells for 7 days, but not 1 day, with 1 mM of lithium or 0.6 mM of valproate significantly reduced rotenone and H2O2-induced cytotoxicity, cytochrome c release and caspase-3 activation, and increased Bcl-2 levels. Conversely, neither acute nor chronic treatment of SH-SY5Y cells with lithium or valproate elicited cytoprotective responses against thapsigargin-evoked cell death and caspase-3 activation. Moreover, inhibitors of glycogen synthase kinase-3 (GSK-3), kenpaullone and SB216763, abrogated rotenone-induced, but not H2O2-induced, cytotoxicity. Thus the cytoprotective effects of lithium and valproate against H2O2-induced cell death is likely independent of GSK-3 inhibition. On the other hand, chronic lithium or valproate treatment did not ameliorate cytotoxicity induced by rotenone, H2O2, and thapsigargin in SVG astroglial and U87 MG glioma cell lines. Our results suggest that lithium and valproate may decrease vulnerability of human neural, but not glial, cells to cellular injury evoked by oxidative stress possibly arising from putative mitochondrial disturbances implicated in bipolar disorder.     

牛蒡苷元对H89诱导的SH—SY5Y细胞损伤的保护作用

目的：考察牛蒡苷元对H89诱导的人神经母细胞瘤SH—SY5Y细胞损伤的保护作用。方法：用蛋白激酶A抑制剂H89处理SH—SY5Y细胞．建立细胞损伤模型。将SH—SY5Y细胞分成正常组（正常细胞）、模型组（经H89处理的细胞）、H89＋牛蒡苷元组（经H89处理后给予牛蒡苷元处理的细胞）和H89＋丹酚酸B组（阳性对照组,经H89处理后给予丹酚酸B处理的细胞）。采用MTT法检测细胞活力、免疫荧光细胞化学法检测细胞中β-淀粉样肽和神经营养因子-3的表达以及Hoechst33258染色法检测细胞凋亡率。结果：H89诱导的细胞损伤模型造模成功。牛蒡苷元在低浓度（0．5μmol·L-1）用最佳,与模型组相比,H89＋低浓度显著提高（P〈0．01）,细胞中β-淀粉样肽的表达下调5．17％（P〈0．05）,而神经营养因子-3的表达上调80．54％（P〈0．01）．凋亡细胞百分比也显著降低（P〈0．05）。结论：低浓度牛蒡苷元对H89诱导的SH-SY5Y细胞损伤具有显著保护作用。     

Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells

Oxidative stress plays an important role in Alzheimer's disease and other neurodegenerative disorders. Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L, shows potent antioxidant property. In this paper, the neuroprotective effects of salidroside on hydrogen peroxide (H2O2)-induced apoptosis in SH-SY5Y cells were investigated. Pretreatment with salidroside markedly attenuated H2O2-induced cell viability loss and apoptotic cell death in a dose-dependent manner. The mechanisms by which salidroside protected neuron cells from oxidative stress included the induction of several antioxidant enzymes, thioredoxin, heme oxygenase-1, and peroxiredoxin-I; the downregulation of pro-apoptotic gene Bax and the upregulation of anti-apoptotic genes Bcl-2 and Bcl-X(L). Furthermore, salidroside dose-dependently restored H2O2-induced loss of mitochondrial membrane potential as well as the elevation of intracellular calcium level. These results suggest that salidroside has protective effects against oxidative stress-induced cell apoptosis, which might be a potential therapeutic agent for treating or preventing neurodegenerative diseases implicated with oxidative stress.     

BAPTA-AM对HepG-2细胞MT的保护作用及其机制

目的观察BAPTA-AM抗H2O2诱导的HepG-2细胞MT损伤作用并探讨其机制。方法采用四甲基偶氮唑盐比色(MTT)、Rhodamine 123(Rh 123))荧光染色、细胞色素C酶联免疫分析、Caspase-9活性检测试剂盒、活性氧ROS检测法分别测定HepG-2细胞活性、线粒体(MT)膜电位、MT细胞色素C(CytC)的释放、Caspase-9的激活、活性氧(ROS)的产生量。结果 BAPTA-AM能抑制H2O2损伤HepG-2细胞所致MT跨膜电位的降低,减少CytC的释放,抑制Caspase-9激活和ROS的生成,提高受攻击H2O2的细胞活力。结论 BAPTA-AM通过减轻钙超载,保护MT,抑制凋亡通路的激活,产生抗细胞损伤、挽救细胞生命之效。     

二氢石蒜碱对过氧化氢损伤的PC12细胞的保护作用

目的:探讨二氢石蒜碱(DL)对H2O2诱导的PC12细胞氧化损伤的影响及其可能机制。方法:用H2O2(200μmol.L-1)处理PC12细胞建立氧化应激模型,并加入二氢石蒜碱预处理作为保护。噻唑蓝(MTT)法和乳酸脱氢酶(LDH)检测细胞存活率和细胞损伤程度,利用荧光探针DCFH-DA和JC-1分别检测细胞内活性氧(ROS)和线粒体膜电位。结果:H2O2作用于PC12细胞后,细胞存活率下降,LDH活性和ROS含量增高,线粒体膜电位降低,与正常对照组比较具有显著性差异(P<0.01);10-7～10-5mol.L-1DL预处理后,细胞存活率提高,LDH和ROS变低,线粒体膜电位回升,且在一定范围呈剂量依赖性。结论:DL对H2O2诱导PC12细胞氧化损伤具有保护作用,其作用机制可能与减少ROS产生和稳定线粒体膜电位有关。     

Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells

Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy.     

Neuronal effects of 4-t-Butylcatechol: a model for catechol-containing antioxidants

Many herbal medicines and dietary supplements sold as aids to improve memory or treat neurodegenerative diseases or have other favorable effects on the CNS contain a catechol or similar 1,2-dihydroxy aromatic moiety in their structure. As an approach to isolate and examine the neuroprotective properties of catechols, a simple catechol 4-t-Butylcatechol (TBC) has been used as a model. In this study, we investigated the effects of TBC on lipopolysaccharide (LPS)-activated microglial-induced neurotoxicity by using the in vitro model of coculture murine microglial-like cell line HAPI with the neuronal-like human neuroblastoma cell line SH-SY5Y. We also examined the effects of TBC on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cells. TBC at concentrations from 0.1-10 microM had no toxic effect on HAPI cells and SH-SY5Y cells, and it inhibited LPS (100 ng/ml)-induced increases of superoxide, intracellular ROS, gp91(Phox), iNOS and a decrease of HO-1 in HAPI cells. Under coculture condition, TBC significantly reduced LPS-activated microglia-induced dopaminergic SH-SY5Y cells death. Moreover, TBC (0.1-10 microM) inhibited 6-OHDA-induced increases of intracellular ROS, iNOS, nNOS, and a decrease of mitochondria membrane potential, and cell death in SH-SY5Y cells. However, the neurotoxic effects of TBC (100 microM) on SH-SY5Y cells were also observed including the decrease in mitochondria membrane potential and the increase in COX-2 expression and cell death. TBC-induced SH-SY5Y cell death was attenuated by pretreatment with NS-398, a selective COX-2 inhibitor. In conclusion, this study suggests that TBC might possess protective effects on inflammation- and oxidative stress-related neurodegenerative disorders. However, the high concentration of TBC might be toxic, at least in part, for increasing COX-2 expression.     

Beta-asarone attenuates beta-amyloid-induced apoptosis through the inhibition of the activation of apoptosis signal-regulating kinase 1 in SH-SY5Y cells

Beta-amyloid (Abeta) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that beta-asarone improves cognitive function by suppressing neuronal apoptosis in vivo. In this study, we assessed the neuroprotective effects of beta-asarone against the toxicity of Abeta in relation to the mitochondria-mediated cell death process, and to elucidated the role of the ASK1/MKK7/JNK and mitochondrial pathways in beta-asarone-induced neuroprotection in SH-SY5Y cells. Our results show that beta-asarone afforded protection against Abeta-induced toxicity by inhibiting apoptosis in SH-SY5Y cells. This result was also confirmed by caspase-9 and caspase-3 activity assays. Expression of p-ASK1, p-MKK7, p-JNK, Bax, Bad, and cytochrome c release decreased after pretreatment with beta-asarone in SH-SY5Y cells exposed to A1-42. Interestingly, these effects of beta-asarone against Abeta1-42 insult were enhanced by ASK1 siRNA. These findings suggest that beta-asarone prevents Abeta1-42-induced neurotoxicity through attenuating neuronal apoptosis, and might be a potential preventive or therapeutic agent for AD.     

MCI-186对β-淀粉样肽诱导SH-SY5Y细胞凋亡及p38MAPK蛋白表达的影响

目的研究依达拉奉(MCI-186)对阿尔茨海默病(AD)细胞损伤的保护作用及其机制。方法将人神经母细胞瘤SH-SY5Y细胞分为五组:空白对照组、溶剂对照组、β淀粉样肽(Aβ)组、Aβ+溶剂对照组和Aβ+药物处理组。用Aβ25-35处理SH-SY5Y细胞,建立AD细胞模型。采用DAPI荧光染色法计数凋亡细胞,Western blot法检测磷酸化的p38丝裂原活化蛋白激酶(p-p38MAPK)表达。结果 Aβ25-35引起时间和剂量依赖性的SH-SY5Y细胞凋亡,并使p-p38MAPK表达增加(P<0.05)。MCI-186与p38MAPK抑制剂SB239063均抑制Aβ25-35诱导的SH-SY5Y细胞凋亡及p-p38MAPK表达(P<0.05)。结论 MCI-186通过抑制p38MAPK磷酸化,对Aβ25-35诱导的SH-SY5Y细胞凋亡起到保护作用。