PI3K/AKT信号通路在偏头痛发病机制中的研究进展

偏头痛是一种临床常见的原发性头痛,因其发病率高、致残率高,对患者的生活质量造成巨大影响,但其发病机制尚不明确。磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)信号通路参与营养代谢、增殖、生长、转录、炎症等细胞活动,在偏头痛的发病机制中具有重要作用。文中介绍PI3K/AKT信号通路在偏头痛发病机制中的作用,旨在为探讨偏头痛的发病机制及治疗靶点等方面提供更多帮助。     

PI3K/AKT信号通路与脑缺血神经细胞凋亡

PI3K/AKT信号通路是重要的细胞存活信号通路,对脑缺血神经细胞凋亡起重要的调控作用。本文就该信号通路对脑缺血损伤的保护作用做一综述。     

PI3K/Akt信号通路在脑缺血神经元凋亡中作用的研究进展

脑缺血发生早期的神经元凋亡与PI3K/Akt信号通路密切相关,通过多种途径干预此信号通路可调控神经元的凋亡,为脑缺血的治疗研究提供靶点,本文就其可能的调控神经元凋亡机制作一综述.     

PI3K/Akt信号通路在癫痫鼠海马神经细胞中的作用及葡萄籽原花青素影响

目的探讨PI3K/Akt信号通路在戊四氮(PTZ)诱导癫痫大鼠海马神经细胞凋亡中的作用及葡萄籽原花靑素(GSPE)对其影响。方法根据是否给予PI3K/Akt信号通路特异性抑制剂LY294002,将大鼠随机分为5组,每组10只:正常对照组、癫痫模型组(PTZ组)、LY294002+PTZ组、GSPE+LY294002+PTZ组、GSPE+PTZ组。采用流式细胞学检测海马组织线粒体膜电位(ΔΨm)水平,Western blot法检测海马组织p-Akt、Caspase 3蛋白的表达变化,电镜观察线粒体的超微结构,以明确GSPE预处理对上述指标的影响。结果与PTZ组相比,LY294002+PTZ组中Caspase 3表达水平显著升高。与LY294002+PTZ组相比,GSPE+PTZ组中p-Akt水平明显升高、Caspase 3蛋白水平明显下降(P0.05),相应海马组织中线粒体ΔΨm的水平升高(P0.05)及超微结构有所改善;而GSPE+LY294002+PTZ组中上述指标则差异无统计学意义。结论 GSPE干预可抑制癫痫鼠海马神经细胞的凋亡并保护线粒体的功能,其机制可能与激活PI3K/Akt信号通路抑制Caspase 3的表达有关。     

孕酮通过PI3K/Akt信号通路减轻新生大鼠缺血缺氧性脑损伤

目的探讨孕酮是否通过PI3K/Akt信号通路减轻新生大鼠缺血缺氧性脑损伤。方法取40只7 d龄新生Wistar大鼠随机分成4组:假手术组:仅做颈部切口,不做缺氧缺血处理;模型组:按动物模型的方法进行缺氧缺血处理;孕酮组:动物进行缺氧缺血处理且在缺氧前30 min按8 mg/kg腹腔注射孕酮溶液;抑制剂组:在建立缺血缺氧性脑损伤模型前30 min,按16μg/kg剂量在大鼠左侧海马区注射Wortmannin。电镜观察新生鼠缺氧缺血性脑损伤神经元的变化,采用免疫组织化学法检测海马pAkt及NF-κB的蛋白表达,应用Western blot检测海马pAkt及NF-κB的蛋白含量。结果 24 h后假手术组神经元结构基本正常,模型组神经元由于缺氧缺血损伤呈空化改变,给予孕酮后的缺氧缺血神经元受损情况改善,空化现象减少,应用抑制剂神经元空化改变明显。缺氧缺血后海马神经元pAkt蛋白表达减少,NF-κB表达增加;孕酮预处理可增加pAkt的表达,降低NF-κB表达;使用抑制剂组pAkt蛋白表达减少,NF-κB表达增加。结论孕酮可通过激活PI3K/Akt信号通路,增加pAkt的水平,抑制NF-κB表达,减轻缺血缺氧性脑损伤中的炎症反应,发挥脑保护作用。     

PI3K/Akt/mTOR信号通路靶向治疗胶质细胞瘤研究进展

脑胶质瘤是中枢神经系统最常见的肿瘤,虽然近年来在胶质瘤的手术技术、化疗、放疗等治疗手段上都取得了长足的进步,但是治疗效果都不是很满意,患者预后仍不容乐观,特别是胶质母细胞瘤患者中位生存期只有8个月[1].随着分子靶向治疗的地位在治疗肿瘤中越来越重要,对胶质瘤中磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)丝/苏氨酸激酶(serine/threonine kinase,Akt)/和哺动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号传导通路(PI3K/Akt/mTOR传导信号通路)及其抑制剂的研究,越来越成为学者们关注的热点.因此本文就PI3K/Akt/mTOR信号通路靶向治疗胶质瘤的研究进展做一综述.     

紫草素通过调控PI3K/AKT通路减轻脑缺血再灌注损伤的机制研究

目的 探讨脑缺血再灌注损伤后PI3K/AKT信号通路的活性变化及紫草素发挥相应作用的调控机制。方法 采用改良的Longa线栓法制作小鼠大脑中动脉缺血再灌注模型。成年雄性CD-1小鼠随机被分为5组:假手术组(Sham)、缺血再灌注组(Vehicle)、低剂量紫草素干预组(L-Shi)、高剂量紫草素干预组(H-Shi)、紫草素+LY294002组(H-Shi+LY294002)。各组小鼠取材前先进行神经功能评分、取材后进行脑梗死体积、脑组织含水量的测定,并对超氧化物歧化酶(SOD)的活性和丙二醛(MDA)含量的变化进行检测,运用免疫组化,蛋白印迹法和实时定量PCR等方法检测缺血侧脑组织中PI3K、AKT、HO-1、Nrf2蛋白和mRNA水平的变化;以及紫草素在脑缺血再灌注损伤中的神经保护作用及其对PI3K/AKT信号转导通路的作用。结果 H-Shi组可明显改善神经功能缺损、降低脑含水量、减小脑梗死体积;免疫组化、Western blot结果显示H-Shi组在24 h和72 h均可明显升高p-PI3K、p-AKT、HO-1、Nrf2的表达,但这种作用同样可被LY294002阻断。H-Shi对...     

PI3 K/Akt信号在阿尔茨海默病样细胞中的作用及依达拉奉对其影响

目的探讨PI3K/Akt信号在β样淀粉蛋白(Aβ1-40)引起的PC12细胞凋亡中的作用及依达拉奉(MCI-186)对其影响。方法采用流式细胞学检测细胞凋亡,Western blot法检测磷酸化Akt及总Akt水平,观察MCI-186对其保护作用。结果模型组中各时间点Akt Ser473的磷酸化水平与对照组比较均降低而保护组各时间点Akt Ser473的磷酸化水平均有明显的升高(P<0.05),保护组中细胞凋亡率较模型组显著降低(P<0.01)。结论Aβ1-40主要通过抑制磷酸化Akt水平,进而诱导PC12细胞凋亡。MC-186通过激活PI3K/Akt信号传导途径,发挥拮抗细胞凋亡的作用,最终达到保护神经细胞的目的。     

PI3K/Akt-eNOS-NO信号通路与脑缺血后适应的研究进展

缺血后适应对缺血性脑卒中具有内源性保护作用,其机制尚未完全阐明.PI3 K/Akt信号通路作为细胞内重要信号转导通路之一,通过影响下游多种效应分子的活化状态,达到对缺血性脑卒中的神经保护作用.缺血后适应通过激活PI3 K/Akt信号通路,从而激活下游内源性eNOS-NO系统,实现多条途径保护缺血脑组织.     

氨甲酰化促红细胞生成素经PI3-K/Akt信号通路抗脑缺血损伤

目的观察脑缺血后氨甲酰化促红细胞生成素(CEPO)的神经保护作用并探讨其可能机制。方法健康雄性SD大鼠随机分为6组(n=10):(1)假手术组;(2)缺血组;(3)EPO组;(4)CEPO组;(5)LY(LY294002)组;(6)CEPO+LY组。应用大脑中动脉线栓法(MCAO)制作大鼠局灶性脑缺血模型,评定大鼠神经功能并计算脑梗死体积,Western blot方法检测PI3-K/Akt活性变化。结果 EPO组与CEPO组脑梗死体积均明显缩小,神经功能显著改善,磷酸化Akt(p Akt)水平明显增高,且两组之间无明显差异,但CEPO的神经保护作用及对Akt磷酸化的诱导效应均可被PI3-K抑制剂LY294002部分抵消。结论 CEPO具有与EPO相当的缺血后脑保护作用,其机制可能与PI3-K/Akt信号通路激活有关。     

Buyang Huanwu decoction enhances cell membrane fluidity in rats with cerebral ischemia/reperfusion

After bilateral carotid artery occlusion for 30 minutes and reperfusion for 2 hours, distinct pathological changes presented in the cerebral cortex and cerebellum of rats. Compared with normal rats, nerve cell membrane fluidity significantly decreased in ischemia/reperfusion rats as detected by spin-labeling electron spin resonance, consistent with order parameter S and rotational correlation time τc measurements. Brain nerve cells from rats with ischemia/reperfusion injury were cultured with 1-100 mg/mL Buyang Huanwu decoction. Results showed that Buyang Huanwu decoction gradually increased membrane fluidity dose-dependently to normal levels, and eliminated hydroxide (OH˙) and superoxide (O2˙) free radicals dose-dependently. These findings suggest that Buyang Huanwu decoction can protect against cell membrane fluidity changes in rats with ischemia/ reperfusion injury by scavenging free radicals.     

补阳还五汤和依达拉奉联用对小鼠急性脑缺血损伤后脑保护机制的研究

目的探讨补阳还五汤和依达拉奉联用对急性脑缺血损伤后神经细胞凋亡及凋亡相关蛋白表达的影响,探讨其可能的脑保护机制。方法将60只小鼠随机分假手术组、模型组、补阳还五汤组、依达拉奉组以及补阳还五汤+依达拉奉组,每组12只。采用改良线栓法制作小鼠大脑中动脉缺血再灌注模型,给予补阳还五汤及依达拉奉药物干预。分别于再灌注后1d和7d,采用TUNEL法观察小鼠脑皮质缺血区神经细胞凋亡率,采用免疫组化方法观察小鼠脑皮质缺血区B淋巴细胞瘤2基因(bcl-2)、bcl-2相关X蛋白(bax)和半胱氨酸蛋白酶3(caspase-3)表达的阳性细胞数。结果与假手术组比较,模型组小鼠脑皮质缺血区凋亡指数升高(P0.01),且bcl-2、bax和caspase-3表达的阳性细胞亦均升高(P0.01);经补阳还五汤和(或)依达拉奉干预后,各药物组小鼠脑组织的凋亡指数及bax和caspase-3阳性细胞均较模型组下降(P0.01),而脑组织bcl-2阳性细胞均较模型组增加(P0.01),且补阳还五汤+依达拉奉联合用药组较单一用药组改变明显(P0.05)。结论补阳还五汤与依达拉奉联用能抑制脑缺血再灌注损伤后脑细胞中促凋亡蛋白bax、caspase-3的表达;促进具有神经元保护作用的bcl-2蛋白的表达,从而抑制神经细胞凋亡,协同发挥脑保护作用。     

补阳还五汤对老龄大鼠脑缺血再灌注海马齿状回细胞增殖分化的影响

BACKGROUND： The mobilization of endogenous stem cells is an effective way to promote repair following ischemic brain damage. Buyang Huanwu decoction （BHD） can effectively improve cerebral blood flow and protect against cerebral ischemia/reperfusion damage. OBJECTIVE： To study the effects of BHD on cell proliferation and differentiation in the hippocampal dentate gyrus of rats following cerebral infarction, to investigate the protective effects of BHD against cerebral infarction, and to analyze the dose-effect relationship. DESIGN, TIME AND SETTING： This randomized, controlled, animal study was performed at the Laboratory of Department of Physiology, Henan College of Traditional Chinese Medicine, China from June 2007 to February 2008. MATERIALS： A total of 36 male, Sprague Dawley rats, aged 20-21 months, were equally and randomly assigned to the following groups： sham operation, model control, and nimodipine, as well as high-dose, moderate-dose, and low-dose BHD. BHD was composed of milkvetch root, Chinese angelica, red peony root, earthworm, peach seed, safflower, and Szechwan Iovage rhizome, which were provided by the Outpatient Department, Henan College of Traditional Chinese Medicine, China. METHODS： The Chinese medicinal ingredients described above were decocted. The external carotid artery was ligated in rats from the sham operation group. Rat models of focal cerebral infarction were established by middle cerebral artery occlusion in the model control and nimodipine groups, as well as the high-dose, moderate-dose, and low-dose BHD groups. The drugs were administered by gavage 5 days, as well as 2 hours, prior to model induction. Rats in the nimodipine group were daily administered a 6 mg/kg nimodipine suspension by gavage. Rats in the high-dose, moderate-dose, and low-dose BHD groups were administered daily 26, 13, and 6.5 g/kg BHD, respectively. Rats in the sham operation and model control groups were treated with an equal volume of saline. MAIN OUTCOME MEASURES： The effects of BHD on neurological dysfunction score, brain water content, cell proliferation and differentiation in the hippocampal dentate gyrus, and pathological changes in the ischemic brain hemisphere were measured in cerebral infarction rats. RESULTS： Compared with the sham operation group, the neurological dysfunction score, brain water content, number of BrdU-positive cells, BrdU/NeuN-positive cells, and BrdU/GFAP-positive cells in the hippocampal dentate gyrus significantly increased in the model control group （P 〈 0.01 ）. Compared with the model control group, neurological dysfunction score and brain water content were significantly decreased （P 〈 0.01 or 0.05）, as were the number of BrdU-positive and BrdU/NeuN-positive cells （P 〈 0.01 or 0.05）. The number of BrdU/GFAP-positive cells was significantly reduced （P 〈 0.05） in the nimodipine group, high-dose, moderate-dose, and low-dose BHD groups. Compared with the nimodipine group, the neurological dysfunction score was significantly reduced in the moderate-dose BHD group （P 〈 0.05）. However, the number of BrdU-positive cells was significantly increased in the rat hippocampal dentate gyrus in the high-dose and moderate-dose BHD groups （P 〈 0.01 or 0.05）. The following was determined by microscopy： slightly disarranged neural cells, mild vascular dilatation, inflammatory cell infiltration, and light tissue edema were observed in the nimodipine group; inflammatory celt infiltration was reduced in the low-dose BHD group; cerebral edema and inflammatory cell infiltration were significantly reduced in the high-dose and in the moderate-dose BHD group. Electron microscopy revealed lipofuscin, slightly swollen mitochondria, and normal rough endoplasmic reticulum in the high-dose and moderate-dose BHD groups. Improvement was best in the moderate-dose BHD group. CONCLUSION： Cerebral ischemia activated proliferation of neural stem cells in the rat hippocampal dentate gyrus. The actions of BHD against cerebral ischemia/reperfusion damage correlated with proliferation and differentiation of neural stem cells in the hippocampal dentate gyrus. A moderate-dose of BHD resulted in the most effective outcome.     

艾地苯醌对帕金森病模型小鼠的神经保护作用及机制

目的探讨艾地苯醌(idebenone)对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病(PD)模型小鼠的神经保护作用及其可能的机制。方法将48只雄性C57/BL6小鼠随机分为正常对照组、PD模型组、艾地苯醌低剂量组以及高剂量组,每组12只。按体重30 mg/kg给予小鼠腹腔注射MPTP(连续5 d)建立PD模型。PD造模前5 d分别按体重100、200 mg/kg给予艾地苯醌低剂量组及高剂量组小鼠艾地苯醌灌胃干预,连续11 d。采用爬杆实验和倒挂实验检测小鼠的运动能力;采用免疫组化法检测各组小鼠黑质区酪氨酸羟化酶阳性(TH⁺)细胞数;采用Western blot检测各组小鼠脑组织B淋巴细胞瘤-2(Bcl-2)、与Bcl-2相关的促凋亡调节因子X(Bax)、半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)、Cleaved-Caspase-3以及磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/AKT)信号通路相关蛋白的表达情况。结果与PD模型组相比,艾地苯醌低、高剂量组小鼠爬杆完成时间明显缩短(P<0.05),脑内Cleaved-Caspase...     

Mitogen activated protein kinase signaling pathways participate in the active principle region of Buyang Huanwu decoction-induced differentiation of bone marrow mesenchymal stem cells

Our preliminary studies confirmed that an active principle region of Buyang Huanwu decoction, comprising alkaloid, polysaccharide, aglycon, glucoside and volatile oil, can induce bone marrow mesenchymal stem cell differentiation into neurons. Mitogen-activated protein kinase signaling was identified as one of the key pathways underlying this differentiation process. The present study shows phosphorylated extracellular signal-regulated protein kinase and phosphorylated p38 protein expression was increased after differentiation. Cellular signaling pathway blocking agents, PD98059 and SB203580, inhibited extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways respectively. mRNA and protein expression of the neuronal marker, neuron specific enolase, and neural stem cell marker, nestin, were decreased in bone marrow mesenchymal stem cells after treatment with the active principle region of Buyang Huanwu decoction. Experimental findings indicate that, extracellular signal-regulated protein kinase and p38 in mitogen-activated protein kinase signaling pathways participate in bone marrow mesenchymal stem cell differentiation into neuron-like cells, induced by the active principle region of Buyang Huanwu decoction.     

基于PI3K/Akt通路研究右美托咪定对癫痫持续状态大鼠海马神经元自噬的调节作用

目的 探讨右美托咪定(Dexmedetomidine,Dex)对癫痫持续状态(Status epilepticus,SE)大鼠海马神经元自噬的调节作用及对磷脂酰肌醇-3-羟激酶/蛋白激酶B(PI3K/Akt)信号通路的影响。方法 采用戊四氮(PTZ)点燃制备SE大鼠模型,随机分为模型组(M组)、Dex低剂量(Dex-L)组、Dex高剂量(Dex-H)组、Dex-H +LY294002(Dex-H+LY)组,另取正常SD大鼠为对照组(NC组),每组各15只; Dex-L组、Dex-H组分别腹腔注射Dex 25、100 μg/kg; Dex-H+LY组脑室注射5 μL PI3K抑制剂LY294002+腹腔注射Dex 100 μg/kg,NC组、M组大鼠腹腔注射等量生理盐水; 观察大鼠行为学表现并进行脑电图描记; 原位末端标记法(TUNEL)检测各组大鼠海马神经元凋亡情况; 免疫印迹(WB)检测各组大鼠海马组织中LC3、PI3K、p-PI3K、Akt、p-Akt蛋白表达水平。结果 NC组大鼠脑电图无异常放电现象,主要以α、β波为主; M组大鼠出现大量阵发性棘波、高幅尖波、棘慢复合波、尖慢复合波等; Dex-L组、Dex-M组大鼠癫痫发作减少或波幅降低; Dex-H+LY组大鼠癫痫样放电较Dex-H组明显增加。与NC组比较,M组大鼠海马神经元凋亡细胞数、海马LC3-Ⅱ蛋白表达显著增加,海马LC3-Ⅰ,p-PI3K/PI3K,p-Akt/Akt蛋白表达水平显著降低(P<0.05); 与M组比较,Dex-L组、Dex-H组大鼠海马神经元凋亡细胞数、海马LC3-Ⅱ蛋白表达依次减少(P<0.05),海马LC3-Ⅰ,p-PI3K/PI3K,p-Akt/Akt蛋白表达水平依次增高(P<0.05); 与Dex-H组比较,Dex-H+LY组大鼠海马神经元凋亡细胞数、海马LC3-Ⅱ蛋白表达显著增加,海马LC3-Ⅰ,p-PI3K/PI3K,p-Akt/Akt蛋白表达水平显著降低(P<0.05)。结论 Dex可能通过促进PI3K/Akt信号通路激活来抑制SE大鼠海马神经元过度自噬,减轻神经元凋亡,发挥抗惊厥及脑保护作用。     

基于PI3K/Akt通路探讨氯吡格雷对脑缺血再灌注损伤大鼠的神经保护作用

目的基于磷酯酰激醇3-激酶/蛋白激酶B(PI3K/Akt)通路探讨氯吡格雷对脑缺血再灌注损伤大鼠的神经保护作用.方法建立脑缺血再灌注大鼠模型,随机分为模型组、氯吡格雷组、LY294002(PI3K抑制剂)组、氯吡格雷+LY294002组,每组12只,另取12只SD大鼠设为假手术组.分组处理后,所有大鼠进行神经功能缺损评分并尾静脉取血,处死大鼠,HE染色检测各组大鼠神经元病理情况;三苯基氯化四氮唑(TTC)染色检测各组大鼠脑组织梗死面积;ELISA检测血清中中枢神经特异性蛋白(S100β)、神经元特异性烯醇化酶(NSE)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平;蛋白免疫印迹法检测脑组织中PI3K/Akt通路蛋白表达情况.结果与假手术组相比,模型组大鼠脑组织神经元出现坏死、核收缩变小等病理变化,神经功能缺损评分、脑梗死面积、血清中S100β、NSE、IL-6及TNF-α水平均明显升高(P<0.05),脑组织中p-PI3K/PI3K、p-Akt/Akt明显降低(P<0.05);与模型组相比,氯吡格雷组大鼠神经元病理损伤减轻,神经功能缺损评分、脑梗死面积、血清中S100β、NSE、IL-6及TNF-α水平均降低(P<0.05),脑组织中p-PI3K/PI3K、p-Akt/Akt升高(P<0.05);LY294002组大鼠神经元病理损伤加重,神经功能缺损评分、脑梗死面积、血清中S100β、NSE、IL-6及TNF-α水平均升高(P<0.05),脑组织中p-PI3K/PI3K、p-Akt/Akt降低(P<0.05).与LY294002组相比,氯吡格雷+LY294002组大鼠神经元病理损伤减轻,神经功能缺损评分、脑梗死面积、血清中S100β、NSE、IL-6及TNF-α水平均降低(P<0.05),脑组织中p-PI3K/PI3K、p-Akt/Akt升高(P<0.05).与氯吡格雷组相比,氯吡格雷+LY294002组大鼠神经元病理损伤加重,神经功能缺损评分、脑梗死面积、血清中S100β、NSE、IL-6及TNF-α水平均升高(P<0.05),脑组织中p-PI3K/PI3K、p-Akt/Akt降低(P<0.05).结论氯吡格雷可通过激活PI3K/Akt通路减轻大鼠脑缺血再灌注损伤,保护脑组织.     

姜黄素通过PI3K/AKT信号通路激活细胞自噬对大鼠颅脑损伤的神经保护作用

目的 探讨姜黄素对颅脑损伤（TBI大鼠）的神经保护作用及其机制。方法 48只成年雄性SD大鼠随机分成假手术组、TBI组、溶媒组、姜黄素组,每组12只。采用重物撞击法制作控制皮质冲击伤模型。造模后,姜黄素组腹腔注射姜黄素（60 mg/kg）,溶媒组腹腔注射姜黄素溶媒磷酸缓冲盐溶液;姜黄素干预72 h采用改良神经功能损伤量表（mNSS）评分评估神经功能;每组取6只大鼠采用Nissl染色评估损伤面积,采用TUNEL染色评估细胞凋亡率;另取6只大鼠免疫印迹法检测PI3K/AKT信号通路以及细胞自噬相关蛋白（LC3、Beclin-1、P62蛋白）表达水平。结果 与假手术组比较,TBI组和溶媒组mNSS评分显著增加（P<0.05）,损伤面积和神经元凋亡率均明显增加（P<0.05）,LC3、Beclin-1表达水平明显增高（P<0.05）,P62表达水平明显降低（P<0.05）,而PI3K和AKT蛋白表达水平无明显变化（P>0.05）;TBI组和溶媒组均无统计学差异（P>0.05）。与溶媒组相比,姜黄素组mNSS评分明显下降（P<0.05）,损伤面积和神经元凋亡率显著降低（P<0.05）,磷酸化PI3K/AKT水平明显增高（P<0.05）,LC3、Beclin-1表达水平明显增高（P<0.05）,P62表达水平明显降低（P<0.05）。结论 姜黄素对TBI大鼠具有显著神经保护作用,机制可能是通过PI3K/AKT信号通路激活自噬