人参皂苷Rg1抗黑质神经元凋亡的可能机制

目的研究人参皂苷Rg1抗1-甲基-4-苯基-1,2,3,6-四氢吡啶(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,MPTP)诱导的小鼠黑质神经元凋亡的作用及其机制。方法MPTP制备的帕金森病(Parkinson′s disease,PD)小鼠模型,经人参皂苷Rg1预处理后,用尼氏(Nissl)染色和TH组化染色观察黑质神经元的损害情况,借助TUNEL染色了解黑质神经元的凋亡情况,并用免疫组织化学方法检测黑质神经元caspase-3的活化以及iNOS和nNOS的表达情况。结果人参皂苷Rg1预处理能减少PD鼠模型黑质致密带Nissl阳性神经元和TH阳性神经元的脱失现象,降低黑质神经元TUNEL染色的阳性率。结论人参皂苷Rg1预处理对MPTP诱导的小鼠黑质神经元凋亡有明显的保护作用。     

人参皂苷Rg1对小鼠1—甲基—4—苯基—1，2，3，6—四氢吡啶诱导的黑质神经元凋亡的保护作用

目的:探讨人参皂苷Rg1对抗1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的C57BL小鼠黑质神经元凋亡的可能机制.方法:MPTP(30 mg·kg~(-1)·d~(-1)×5 d)腹腔注射制备C57BL小鼠帕金森病模型,同时预防组分别以不同剂量人参皂苷Rg1(2.5、5.0、10.0 mg·kg~(-1)·d~(-1)×8 d)于MPTP注射前预先腹腔注射小鼠.用Nissl染色和TH组化染色观察黑质损害情况,TUNEL染色检测细胞凋亡,同时运用免疫组织化学方法检测caspase-3的活性片段以及Bcl-2、Bcl-xl、Bax、iNOS和 nNOS的表达情况.结果:人参皂苷Rg1(5.0和10.0 mg/kg)预处理能使黑质致密带Nissl阳性神经元和TH阳性神经元的脱失减少,同时降低了TUNEL阳性率,并伴有Bcl-2和Bcl-xl表达增加,Bax和iNOS表达减少以及抑制caspase-3的激活.结论:人参皂苷Rg1预处理对MPTP诱导的小鼠黑质神经元凋亡有明显的保护作用,其作用可能是通过降低iNOS和Bax蛋白表达,增加Bcl-2和Bcl-xl蛋白表达以及抑制caspase-3的激活来实现的.     

Astaxanthin protects against MPTP/MPP+-induced mitochondrial dysfunction and ROS production in vivo and in vitro

Astaxanthin (AST) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. We have investigated the role of AST in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of the substantia nigra (SN) neurons in the mouse model of Parkinson’s disease (PD) and 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity of SH-SY5Y human neuroblastoma cells. In in vitro study, AST inhibits MPP+-induced production of intracellular reactive oxygen species (ROS) and cytotoxicity in SH-SY5Y human neuroblastoma cells. Preincubation of AST (50 μM) significantly attenuates MPP+-induced oxidative damage. Furthermore, AST is able to enhance the expression of Bcl-2 protein but reduce the expression of α-synuclein and Bax, and suppress the cleavage of caspase-3. Our results suggest that the protective effects of AST on MPP+-induced apoptosis may be due to its anti-oxidative properties and anti-apoptotic activity via induction of expression of superoxide dismutase (SOD) and catalase and regulating the expression of Bcl-2 and Bax. Pretreatment with AST (30 mg/kg) markedly increases tyrosine hydroxylase (TH)-positive neurons and decreases the argyrophilic neurons compared with the MPTP model group. In summary, AST shows protection from MPP+/MPTP-induced apoptosis in the SH-SY5Y cells and PD model mouse SN neurons, and this effect may be attributable to upregulation of the expression of Bcl-2 protein, downregulation of the expression of Bax and α-synuclein, and inhibition of the activation of caspase-3. These data indicate that AST may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson’s disease.     

人参皂苷Re对MPTP致帕金森病模型小鼠多巴胺能神经元的保护作用

目的研究人参皂苷Re对 1 甲基 4 苯基 1,2 ,3,6 四氢吡啶 (1 methy 4 phenyl 1,2 ,3,6 te trahydropyridine ,MPTP)诱致帕金森病模型小鼠多巴胺能神经元的保护作用及其可能机制。方法通过给C5 7BL小鼠皮下注射MPTP制备帕金森病 (parkinson’sdisease ,PD)模型 ,灌胃给予人参皂苷Re预处理后 ,运用逆转录 聚合酶链式反应 (RT PCR)、免疫组织化学染色以及图像分析等技术分别对纹状体前脑啡肽原 (preproenkephalin ,PPE)mRNA、前强啡肽原 (preprodynorphin ,PPD)mRNA的表达水平和黑质酪氨酸羟化酶 (TH)、γ 氨基丁酸 (GABA)免疫反应阳性神经元数目等多项指标进行考察。结果Re能使黑质致密部 (SNc)的TH阳性神经元和黑质网状部 (SNr)的GABA阳性神经元数目显著增多 ;Re高剂量预防组 (2 6mg·kg-1)PPD扩增产物较模型组显著增加 (P <0 0 5 ) ;Re预防组的PPE扩增产物与模型组比没有显著差异。结论人参皂苷Re对MPTP诱致帕金森病小鼠黑质多巴胺能神经元具有明显的保护作用 ,其作用可能与改变GABA能神经元以及PPDmRNA表达水平 ,从而调节PD中直接回路和间接回路的兴奋 抑制平衡有关     

Apoptotic molecules and MPTP-induced cell death

MPTP-induced neurotoxicity is one of the experimental models most commonly used to study the pathogenesis of Parkinson's disease (PD). MPTP administered in vivo to mice causes selective loss of dopaminergic neurons in the substantia nigra (SN), as in this disease. Cell death may be induced in vitro by MPP(+), the active metabolite of MPTP, when neuronal cell cultures are used. Biochemical mechanisms underlying cell death induced by MPTP/MPP(+) still remain to be clarified completely. This article reviews some recent findings linking the effects of MPTP/MPP(+) with molecules typically involved in apoptotic pathways. This type of research has made extensive use of genetically manipulated systems such as transgenic mice and transfected cell lines. Evidence has emerged to suggest that Bcl-2, Bax, JNK, and caspases are implicated in neurotoxic effects due to in vivo MPTP administration to mice. Different neuronal cell lines such as MN9D cells, SH-SY5Y cells, cerebellar granule neurons, cortical neurons, and GH3 cells were also tested to investigate the possible involvement of Bcl-2, Bax, and caspases in in vitro MPP(+)-induced neurotoxicity.     

Ginsenoside Rg1 reduces MPTP-induced substantia nigra neuron loss by suppressing oxidative stress

AIM: To investigate the effect of ginsenoside Rg1, an effective ingredient from ginsenoside, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced substantia nigra neuron lesion. METHODS: C57-BL mice were given MPTP to prepare Parkinson disease mice model. Different doses of Rg1 (5, 10, and 20 mg.kg(-1).d(-1)) or N-acetylcystein (NAC) (300 mg.kg(-1).d(-1)) were given 3 d prior to MPTP in the pretreatment groups. Glutathione (GSH) level and total superoxide dismutase (T-SOD) activity in substantia nigra were determined by spectrophotometry. Nissl staining, tyrosine hydroxylase immunostaining, and TUNEL labeling were used to observe the damage and apoptosis of nigral neurons. Western blot analysis was used to detect the phospho-JNK and phospho-c-Jun levels in midbrain homogenates. RESULTS: Pretreatments of C57-BL mice with different doses of Rg1 or NAC were found to protect against MPTP-induced substantia nigra neurons loss. Rg1 or NAC prevented GSH reduction and T-SOD activation in substantia nigra, and attenuated the phosphorylations of JNK and c-Jun following MPTP treatment. CONCLUSION: The antioxidant property of Rg1 along with the blocking of JNK signaling cascade might contribute to the neuroprotective effect of ginsenoside Rg1 against MPTP.     

艾司西酞普兰对帕金森病大鼠运动行为学及黑质多巴胺神经元的影响

目的 观察艾司西酞普兰(ESC)对帕金森病(PD)大鼠运动行为学及黑质多巴胺神经元的影响,并探讨可能机制.方法 将30只PD大鼠随机分为PD组、ESC组、ESC+LY294002组,各10只.另10只仅做假手术,设为Sham组.造模成功后,ESC组给予ESC 10 mg·kg-1(溶于生理盐水),灌胃;ESC+LY29...     

异甘草酸镁对四氯化碳诱导肝损伤大鼠肝组织Bax、Bcl-2蛋白表达及肝纤维化指标影响

目的:观察异甘草酸镁注射液对四氯化碳诱导肝损伤大鼠肝组织Bax、Bcl-2蛋白表达及纤维化指标的影响.方法:50只大鼠随机分成正常对照组(NS组)、肝损伤模型组(MO组)、异甘草酸镁注射液高剂量组(H组)、异甘草酸镁注射液中剂量组(M组)、异甘草酸镁注射液低剂量组(L组),每组10只.MO组和各给药组大鼠将50％ CC...     

SIRT3介导褪黑激素保护帕金森病多巴胺能神经元的作用机制

目的研究SIRT3在褪黑激素保护帕金森病(Parkinson’s disease,PD)多巴胺能神经元中的作用。方法48只小鼠随机分为对照组、模型组和治疗组,治疗组小鼠给予褪黑激素(10 mg·kg-1)和MPTP(30 mg·kg-1)腹腔注射,模型组小鼠给予MPTP腹腔注射,对照组小鼠同时给予等量生理盐水,褪黑激素连续给药14 d。采用免疫组化分析黑质TH、Iba-1表达情况,ELISA法检测中脑组织氧化应激指标(ROS、MDA、SOD)及炎症因子(TNF-α、IL-1β)水平,实时定量PCR分析SIRT3 mRNA水平,免疫荧光和Western blot检测蛋白表达情况。结果与对照组比较,模型组小鼠黑质TH表达减少、Iba-1表达增多,中脑组织氧化应激与炎症损伤明显增强,黑质SIRT3 mRNA和蛋白表达水平明显降低,SOD2蛋白表达减少,iNOS蛋白表达增多,组间比较差异均具有统计学意义( P <0.05)。治疗组小鼠经褪黑激素干预后,TH表达增多、Iba-1表达减少,氧化应激与炎症损伤明显减弱,SIRT3 mRNA和蛋白表达水平升高,SOD2蛋白表达上调,iNOS蛋白表达下调,与模型组比较,差异均具有统计学意义( P <0.05)。 结论 褪黑激素通过上调SIRT3表达抵抗PD多巴胺能神经元损伤,作用机制与其抑制小胶质细胞激活减轻氧化应激和炎症损伤有关。     

Three new and two rare furanoeremophilanes from Senecio asirensis

Three new furanoeremophilanes have been obtained from the aerial parts of Senecio asirensis (N. O. Asteraceae), and characterized as 6-hydroxylmethyl-9-methoxyl-4,11-dimethylnaphtho[2,3-b]furan, designated asirensane-a (1), 6-hydroxyl-1,2-dimethoxyl-4,6,11-trimethyl-6-hydronaphtho[2,3-a]furan-7-one, named asirensane-b (2), and (6,12-dihydroxyl-9-methoxyl-4-methyl-11-acetyl-3,4-dihydronaphtho[2,3-b]furan-3-yl)methyl (2'Z)-2'-methylbut-2'-enoate, designated asirensane-c (3). In addition, two rare furanoeremophilanes have also been isolated and characterized from this source, namely 9-methoxyl-4,11-dimethylnaphtho[2,3-b]furan, named 14-nordehydrocalohastine (4), and 4,11-dimethylnaphtho[2,3-b]furan-6,9-dione, designated as maturinone (5). Their structures have been elucidated on the basis of spectral analysis. The alcoholic extract was also tested for anti-inflammatory activity, which decreased edema by 22% at a dose of 500 mg kg^-1 after 3 h with respect to the control group treated only with carrageenan, while the standard drug phenylbutazone showed a 50% decrease at a dose of 100 mg kg^-1, indicating that the extract has moderate anti-inflammatory activity.     

小檗碱衍生物9-OH小檗碱的抗帕金森病活性和作用机制研究

目的: 探究小檗碱衍生物9-OH小檗碱对1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride,MPTP)诱导的斑马鱼帕金森病(Parkinson’s disease,PD)症状是否具有缓解作用。方法: 受精后1 d (day post fertilization,dpf)的斑马鱼胚胎,设置空白对照组,50 μmol·L^-1 MPTP造模组,50 μmol·L^-1 MPTP与不同质量浓度(100,300,500 μmol·L^-1)9-OH小檗碱共处理组。4 dpf时,分别观察并记录各组斑马鱼多巴胺神经元及脑部血管的发育情况;5 dpf时,监测行为学,记录各组行为学数据并分析差异,收集后检测PD相关基因表达变化,包括编码α-突触核蛋白(α-synuclein,α-Syn)的α-syn、编码E3泛素连接酶(E3 ubiquitin protein ligase,Parkin)的parkin、编码自噬相关基因5(autophagy related gene 5,Atg5)的atg5、编码微管相关蛋白1轻链3B (microtubule-associated protein 1 light chain 3B,Lc3b)的lc3b。结果: MPTP造模组的斑马鱼多巴胺神经元和脑部血管出现不同程度的损伤,且出现运动迟缓、焦虑等PD状行为,与PD相关的基因表达也出现异常;而MPTP与9-OH小檗碱共处理组的斑马鱼多巴胺神经元和脑部血管的损伤得到改善,行为学能力得到恢复,且PD相关基因的表达趋于正常。结论: 小檗碱衍生物9-OH小檗碱对MPTP诱导的斑马鱼帕金森病症状有缓解作用。     

RY10-4对乳腺癌MCF-7裸鼠移植瘤的抑制作用及其机制

目的:探讨2-(1-羟基-4-酮-2,5-环己二烯)-吡喃-4-酮(RY10-4)对乳腺癌裸鼠移植瘤抑制作用及其可能的作用机制。方法:建立乳腺癌(MCF-7)裸鼠移植瘤模型,将造模裸鼠随机分为模型组、RY10-4低剂量组(7.5 mg·kg^-1)、 RY10-4高剂量组(15 mg·kg^-1)和紫杉醇组(15 mg·kg^-1);各组均采取隔天腹腔注射给药,检测各组荷瘤裸鼠移植瘤体积和体质量变化。给药16 d后,处死所有裸鼠,称取各组移植瘤质量,TUNEL法检测凋亡指数,并通过Western blot测定移植瘤中Bcl-2、Bax和MAPK 通路蛋白的表达。结果:与模型组比较,RY10-4低、高治疗组和紫杉醇组瘤体积明显减小,瘤质量明显减轻,抑瘤率分别为29.8%,47.2%,53.8%。TUNEL法结果显示,各治疗组能明显引起移植瘤细胞凋亡(P<0.01)。Western blot结果显示,随着RY10-4治疗量的增加抗凋亡蛋白Bcl-2表达减弱,促凋亡蛋白Bax的表达增强,Bcl-2/Bax值显著下降,与模型组相比差异均有统计学意义(P<0.05);另外,RY10-4治疗组移植瘤细胞中的p-p38和p-ERK表达量明显增加。结论:RY10-4能够抑制乳腺癌移植瘤的生长和诱导乳腺癌细胞的凋亡,其诱导凋亡作用可能与下调Bcl-2蛋白和上调Bax蛋白,降低Bcl-2/Bax值,并激活p38和ERK信号通路有关。     

Effect of angiotensin-converting enzyme inhibitor perindopril on interneurons in MPTP-treated mice.

We examined the effects of perindopril on the dopaminergic system in mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. The mice received four intraperitoneal injections of MPTP at 1-h intervals. Administration of perindopril showed dose-dependent neuroprotective effects against striatal dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletion 3 days after MPTP treatment. Our immunohistochemical study showed that MPTP can severe damage in tyrosine hydroxylase (TH)-immunoreactive neurons after MPTP treatment. The administration of perindopril significantly attenuated MPTP-induced substantia nigra and striatal damage. The present study also showed that the immunoreactivity of parvalbumin (PV)- or neuronal nitric oxide synthase (nNOS)-positive cells in the substantia nigra was decreased 7 days after MPTP treatment, whereas no significant changes were observed in these cells of the striatum throughout the experiments. The administration of perindopril significantly attenuated MPTP-induced decrease of the PV- or nNOS-immunoreactivity in the nigral cells. In double-labeled immunostaining with anti-PV and anti-nNOS antibody, PV-immunoreactive cell bodies and fibers were not double-labeled for nNOS-immunoreactive cell bodies and fibers in both the striatum and substantia nigra after MPTP treatment. Furthermore, PV- or nNOS-immunoreactive cell bodies and fibers in both the striatum and substantia nigra were not double-labeled for TH-immunoreactive cell bodies and fibers. These results demonstrate that the ACE inhibitor perindopril has a dose-dependent protective effect against MPTP-induced striatal dopamine, DOPAC and HVA depletion in mice. The present study also demonstrates that perindopril is effective against MPTP-induced degeneration of the nigral neurons and interneurons. Furthermore, our immunohistochemical study suggests that PV-immunoreactive cells and nNOS-immunoreactive cells are different interneurons in both the striatum and substantia nigra. Thus, our results provide further evidence that the ACE inhibitor perindopril may offer a novel therapeutic strategy for Parkinson's disease (PD).     

积雪草苷对大鼠心肌缺血再灌注损伤的保护作用以及MAPK通路的影响

目的：研究积雪草苷对大鼠心肌缺血再灌注损伤及MAPK信号通路的影响。方法：构建大鼠心肌缺血再灌注模型,将大鼠分为对照组、模型组和积雪草苷低（12.5 mg·kg^-1）、中（25 mg·kg^-1）、高（50 mg·kg^-1）治疗组。心脏超声检测心脏功能,HE染色检测心脏组织损伤程度。免疫组化检测心脏组织中ki67阳性细胞率,Western blot检测Bax、Bcl-2、磷酸化-细胞外调节激酶1/2（phosphorylation-extracellular signal-regulated kinase 1/2,p-ERK1/2）和p-p38丝裂原活化蛋白激酶（p-p38 mitogen-activated protein kinase,p-p38MAPK）的蛋白相对表达量。酶联免疫吸附法（enzyme-linked immunosorbent assay,ELISA）检测外周血液中肌酸激酶同工酶（creatine kinase-MB,CK-MB）、肌红蛋白（myoglobin,Mb）、肌钙蛋白（cardiac troponin I,cTnI）、肿瘤坏死因子-α（tumor necrosis factor alpha,TNF-α）、白介素-6（interleukin-6,IL-6）和IL-1β的蛋白相对表达量。结果：与模型组相比,在积雪草苷治疗后,大鼠心率、射血分数、左室收缩压显著上调;心肌酶Mb、cTnl、CK-MB的表达量显著下调,ki67阳性细胞率上调,促炎细胞因子IL-6、TNF-α和IL-1β的表达量下调,Bax/Bcl-2、p-ERK1/2/ERK1/2和p-p38MAPK/p38MAPK的比率显著下调。结论：积雪草苷对大鼠心肌缺血再灌注损伤的保护作用,并抑制MAPK信号通路。     

葱白提取物对心肌缺血-再灌注损伤大鼠的保护作用及其机制

目的探讨葱白提取物(FOB)预处理对大鼠心肌缺血-再灌注(I/R)损伤的保护作用及其机制。方法SD成年大鼠随机分为假手术组,I/R组,FOB(小、中、大剂量)(300,600,1200 mg·kg^-1)+I/R组和硝酸甘油+I/R组,每组10只;结扎左冠状动脉前降支30 min再灌注24 h建立在体心肌I/R损伤模型。多导生理记录仪记录和分析左心室功能变化;酶联免疫吸附测定(ELISA)法检测大鼠血清肌酸激酶(CK)、乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)水平;Western blotting和实时-聚合酶链反应(RT-PCR)检测心肌Bax和Bcl-2蛋白及mRNA表达水平;免疫荧光检测细胞色素C(Cyt-C)和凋亡酶激活因子1(Apaf-1)的表达。结果与I/R组比较,FOB(小、中、大剂量)+I/R组大鼠心功能均明显改善;CK、LDH和CK-MB浓度降低;Bax蛋白及mRNA表达水平下调,同时Bcl-2蛋白及mRNA表达水平升高;Cyt-C及Apaf-1蛋白表达下降(P<0.05),并存在一定量效关系。结论FOB具有显著改善大鼠心肌I/R损伤及拮抗心肌细胞凋亡的作用,其机制与调节心肌Bax、Bcl-2、Cyt-C和Apaf-1的表达密切相关。     

线粒体融合素2通过Ras-PI3K-Akt信号途径抑制缺血再灌注诱导的乳鼠心肌细胞凋亡

目的：研究线粒体融合素2（Mfn2）基因对缺血再灌注诱导的乳鼠心肌细胞凋亡的影响及其相关的信号通路。方法：乳鼠心肌细胞经缺氧/复氧（H/Re）处理模拟心肌缺血再灌注损伤。用Mfn2基因的重组腺病毒（Adv-Mfn2）感染经缺氧复氧处理的乳鼠心肌细胞。采用TUNEL染色、ELISA、流式细胞术等方法检测Mfn2对缺血再灌注诱导的乳鼠心肌细胞凋亡的影响。Western blot分析线粒体凋亡路径中Bcl-2蛋白、Bax蛋白、Caspase-9以及磷酸化蛋白激酶B（p-Akt）的表达变化。结果：TUNEL染色发现Adv-Mfn2感染乳鼠心肌细胞后,细胞凋亡较H/Re组和Adv-LacZ组显著减少。ELISA和流式细胞仪检测结果表明,Adv-Mfn2组心肌细胞凋亡较H/Re组及Adv-LacZ组明显减少,且这一作用呈时间依赖性。Western blot结果显示,Adv-Mfn2组中Bcl-2蛋白表达较H/Re组和Adv-LacZ感染组上升,Bax蛋白表达下降,各组中Caspase-9的表达变化与Bax相同,Adv-Mfn2组的p-Akt蛋白表达水平则较H/Re组和Adv-LacZ感染组明显上升。结论：Mfn2基因主要通过正向调控RasPI3K-Akt信号通路,促进Akt的磷酸化水平,使Bcl-2蛋白表达量增加,Bax蛋白表达量降低,抑制Caspase-9活化,从而抑制缺血再灌注诱导的乳鼠心肌细胞凋亡。     

法舒地尔对抑郁症的调节机制研究

目的：探究法舒地尔对抑郁症大鼠的保护作用及对海马神经细胞凋亡和微血管密度的影响。方法：40只SD大鼠随机分为对照组（n=10）、模型组（n=10）、法舒地尔组（n=10）和氟西汀组（n=10）。采用慢性温和不可预知性应激（chronic unexpected mild stress,CUMS）程序构建大鼠抑郁模型。法舒地尔组给予30 mg·kg^-1的法舒地尔;氟西汀组给予1.54 mg·kg^-1氟西汀,每日灌胃1次;对照组及模型组大鼠注射同等剂量的纯化水,每日灌胃1次,连续给药4 d。检测各组大鼠行为学的变化（如糖水消耗、强迫游泳）;酶联免疫吸附法检测各组大鼠海马组织中5-羟色胺（5-HT）和多巴胺（DA）的水平;TUNEL染色法检测海马区神经细胞凋亡情况;Western印迹法分别检测天冬氨酸蛋白水解酶-3（Caspase-3）、cleaved Caspase-3、B细胞淋巴瘤-2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）的蛋白表达;免疫组化法检测大鼠海马区S100B、CD34的分布和表达,并计算微血管密度（MVD）。结果：相比于对照组,模型组大鼠糖水偏爱指数明显下降,强迫游泳实验中静止不动时间明显延长,大鼠海马组织5-HT、DA水平明显降低,cleaved Caspase-3、Bax的蛋白表达明显升高,海马神经细胞凋亡数亦显著增高（P<0.05）,Bcl-2蛋白水平下调,MVD下降（P<0.05）。而法舒地尔和氟西汀预处理能显著抑制这些变化（P<0.05）,且法舒地尔组的整体抑制效果更佳。结论：法舒地尔可有效改善大鼠抑郁症状,这可能与其抑制海马区神经细胞凋亡,下调cleaved Caspase-3、Bax水平,上调Bcl-2水平,改善血管微循环有关。     

A new triterpene from Luculia pinciana Hook

A new triterpene named luculiaoic acid A (1), showing inhibitory activity of a leukaemia cell line, along with eleven known compounds, has been isolated from the ethyl acetate extract of the stems of Luculia pinciana Hook. All the structures were elucidated on the basis of NMR, MS, and IR methods. The activity to inhibit Staphylococcus aureus and Candida albicans of all compounds showed that ursolic acid inhibits the growth of Staphylococcus aureus with an MIC of 0.5 mg ml^-1 and an MBC of 10 mg ml^-1, and scopletin inhibits Candida albicans with an MIC of 1 mg ml^-1 and an MBC of 5 mg ml^-1.     

Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson’s Disease

Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson’s disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-mediated inflammation and nigrostriatal neurodegeneration in cellular and animal models of PD. Mito-Apo treatment in primary mesencephalic cultures significantly attenuated the 1-methyl-4-phenylpyridinium (MPP⁺)-induced loss of tyrosine hydroxylase (TH)-positive neuronal cells and neurites. Mito-Apo also diminished MPP⁺-induced increases in glial cell activation and inducible nitric oxide synthase (iNOS) expression. Additionally, Mito-Apo decreased nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE) levels in primary mesencephalic cultures. Importantly, we assessed the neuroprotective property of Mito-Apo in the MPTP mouse model of PD, wherein it restored the behavioral performance of MPTP-treated mice. Immunohistological analysis of nigral dopaminergic neurons and monoamine measurement further confirmed the neuroprotective effect of Mito-Apo against MPTP-induced nigrostriatal dopaminergic neuronal loss. Mito-Apo showed excellent brain bioavailability and also markedly attenuated MPTP-induced oxidative markers in the substantia nigra (SN). Furthermore, oral administration of Mito-Apo significantly suppressed MPTP-induced glial cell activation, upregulation of proinflammatory cytokines, iNOS and gp91phox in IBA1-positive cells of SN. Collectively, these results demonstrate that the novel mitochondria-targeted compound Mito-Apo exhibits profound neuroprotective effects in cellular and pre-clinical animal models of PD by attenuating oxidative damage and neuroinflammatory processes.     

雷公藤内酯醇对雄性大鼠生殖毒性的机制研究(Ⅱ)

目的：考察雷公藤内酯醇对大鼠睾丸细胞相关凋亡基因mRNA表达的影响,研究雷公藤内酯醇生殖毒性的分子机制。方法：以低（0.025 mg·kg^-1）、中（0.05 mg·kg^-1）、高（0.1 mg·kg^-1）剂量的雷公藤内酯醇对健康雄性Wistar大鼠连续灌胃染毒30 d,每天一次,于末次染毒24 h后处死大鼠,取睾丸组织进行病理学检查,并通过实时荧光定量PCR测定Bcl-2、Bax、Fas、FasL、CREM和Caspase-3基因mRNA的表达情况。结果：与阴性对照组相比,雷公藤内酯醇染毒组睾丸组织生精细胞明显减少,精索内几乎无精子;高剂量组Bcl-2、CREM mRNA表达降低;而Bax mRNA表达水平在中、高剂量组时呈显著地高表达;Fas和FasL mRNA表达水平在高剂量组显著上升;Caspase-3 mRNA表达水平呈现依赖剂量的高表达,中、高剂量时呈现显著性差异。结论：提示在本实验染毒剂量范围内,特别是高剂量的雷公藤内酯醇能够使生殖细胞相关凋亡基因Bcl-2、Bax、Fas、FasL、CREM和Caspase-3不同程度的表达异常,这很可能是雷公藤内酯醇诱导大鼠生殖细胞凋亡的重要原因,为进一步深入阐述雷公藤内酯醇雄性生殖毒性的分子机制提供了依据。