淫羊藿苷抑制β-catenin 和NF-κB p65 的活性对小鼠胰腺癌皮下移植瘤生长和运动的调节

目的:研究淫羊藿苷调控小鼠胰腺癌皮下移植瘤生长和运动的机制。方法:建立BALB/c小鼠皮下胰腺癌移植瘤模型后,分别给予生理盐水(对照组)、10 mg/kg淫羊藿苷(低剂量组)、20 mg/kg淫羊藿苷(中剂量组)、40 mg/kg淫羊藿苷(高剂量组)、5 mg/kg阿霉素(阿霉素组)腹腔给药干预,干预25 d后取出瘤体,检测瘤体重量和体积,并根据小鼠存活情况绘制生存曲线;TUNEL染色观察瘤组织凋亡情况,免疫组化检测Ki67、血管内皮生长因子(VEGF)蛋白阳性表达率;qRT-PCR检测瘤组织中生长和运动标记分子基因相对表达情况,Western blot检测Wnt/β-catenin和核因子κB(NF-κB) p65信号通路关键蛋白表达情况。结果:与对照组相比,中、高剂量淫羊藿苷及阿霉素干预后,移植瘤的重量、体积,瘤组织中Ki67、VEGF的阳性表达率,Ki67、VEGF、基质金属蛋白酶-9(MMP-9)的mRNA相对表达量,β-catenin蛋白表达量、NF-κB p65蛋白磷酸化水平均显著降低(P0.05),小鼠的25 d存活率、瘤组织细胞凋亡率以及Caspase-3的mRNA相对表达量均显著升高(P0.05)。结论:淫羊藿苷可能通过抑制β-catenin和NF-κB p65的活性下调增殖及运动相关基因表达,上调凋亡相关基因表达从而调节小鼠胰腺癌皮下移植瘤的生长和运动。     

淫羊藿苷调节酸性微环境减轻绝经后老年骨质疏松性疼痛

背景：前期研究已证明，淫羊藿苷在促进骨形成和抑制骨吸收方面具有重要作用，但其对骨质疏松介导的骨痛产生的影响尚未见报道。目的：探讨淫羊藿苷减轻绝经后老年性骨质疏松性骨痛的可能机制。方法：(1)动物实验：将200只C57BL/6小鼠随机分为4组：假手术组、模型组、模型+淫羊藿苷组，模型+碳酸酐酶Ⅱ抑制剂组。除假手术组外，其余各组摘除小鼠卵巢建立绝经后骨质疏松模型。模型+淫羊藿苷组在造模后第2天灌胃淫羊藿苷，每2周进行1次疼痛行为学实验并取材，持续20周。microCT检测股骨骨量、苏木精-伊红染色及TRAP染色检测破骨细胞活性、免疫荧光染色检测神经元形态及相关离子通道表达。(2)细胞实验：提取小鼠骨髓来源的破骨细胞前体细胞，在体外使用RANKL/M-CSF体系诱导分化为破骨细胞并添加不同浓度淫羊藿苷(1,10μmol/L)干预。采用抗酒石酸酸性磷酸酶染色检测破骨细胞分化，采用鬼笔环肽染色检测破骨细胞肌动蛋白环，采用骨板吸收实验检测破骨细胞噬骨功能，采用pH计检测体系pH值，采用Western Blot检测破骨细胞分化相关蛋白表达。此外，提取小鼠背根神经节来源神经细胞并用淫羊藿苷处理，采用C...     

淫黄葛复合剂对阿尔茨海默病小鼠行为学和海马解聚素金属蛋白酶10表达的影响

目的 探讨淫羊藿、黄芪、葛根有效组分复方对阿尔茨海默病（AD）模型小鼠行为学和海马CA3区解聚素金属蛋白酶10（ADAM10）表达的影响。方法 10月的雄性APPswe/PS1dE9双转基因模型小鼠30只随机分为复方组、模型组和去铁斯诺(DFX)组,10月龄的雄性C57BL/6 J小鼠10只作为正常对照组。用药结束后,采用Morris水迷宫检测各组小鼠学习记忆能力,并于水迷宫后取出小鼠的脑组织,应用免疫荧光、Real-time PCR和Western blotting方法检测各组小鼠海马CA3区ADAM10的表达。结果 水迷宫实验结果显示,与正常对照组小鼠相比,模型组小鼠的逃避潜伏期、游泳距离和游泳时间均明显延长(P＜0.05),穿越平台区域次数和平台区域停留时间明显减少(P＜0.05),首次穿越平台的逃避潜伏期明显延长(P＜0.05);与模型组小鼠相比,复方组和DFX组逃避潜伏期、游泳距离和游泳时间明显缩短(P＜0.05),穿越平台区域次数和平台区域停留时间明显增多(P＜0.05),首次穿越平台的逃避潜伏期明显缩短;复方组和DFX组相比,逃避潜伏期、游泳距离和游泳时间及跨台次数差异无显著性 (P＞0.05),穿越平台区域次数、平台区域停留时间和首次穿越平台的逃避潜伏期差异无显著性 (P＞0.05)。与正常对照组小鼠相比,模型组小鼠海马CA3区ADAM10的表达增高(P＜0.05);与模型组相比,复方组和DFX组小鼠海马CA3区DAM10的表达降低(P＜0.05);复方组和DFX组相比,ADAM10表达水平差异无显著性 (P＞0.05)。结论 应用淫羊藿、黄芪、葛根有效组分复方可以改善APPswe/PS1dE9双转基因AD模型小鼠的学习记忆能力,其机制可能与下调ADAM10的表达减少神经元的损伤和死亡有关。     

中药淫羊藿苷干预人工关节磨损微粒诱导的骨溶解

背景：人工关节周围产生骨溶解是关节松动失败的重要原因,各国学者都在寻求一种能有效抑制骨溶解反应的药物,以减少假体松动的发生。 目的：观察不同剂量淫羊藿苷干预人工关节磨损微粒诱导骨溶解的效果。 方法：将钛合金及骨水泥磨损微粒制成的混悬液分别置入清洁小鼠颅盖骨进行骨溶解建模后,空白组滴入生理盐水到颅盖骨中,药物干预组给予不同浓度的淫羊藿苷(剂量分别为30,60,120 mg/kg)灌胃,每日1次。建模2周后处死小鼠,在显微镜下观察小鼠颅盖骨的结构。经苏木精-伊红染色和免疫组化分析计算破骨细胞数量和小鼠颅盖骨溶解面积的变化。 结果与结论：与空白组比较,钛合金微粒和骨水泥微粒建模后的小鼠颅盖骨切片上的骨溶解陷窝数量及破骨细胞数明显增加,图像分析骨溶解陷窝面积也增大(P < 0.05)。淫羊藿苷干预后骨溶解面积减小及破骨细胞数量减少  (P < 0.05),以120 mg/kg灌胃组最为显著,其次是60 mg/kg,30 mg/kg。结果可见钛磨损微粒和骨水泥磨损微粒能促进破骨细胞的增殖,诱导骨溶解;淫羊藿苷能抑制磨损微粒诱导的破骨细胞形成,从而抑制骨溶解。中国组织工程研究杂志出版内容重点：人工关节;骨植入物;脊柱;骨折;内固定;数字化骨科;组织工程全文链接：     

淫羊藿苷改善甲状腺功能减退模型大鼠的垂体发育

背景：甲状腺功能减退常伴随着垂体合成分泌激素分泌不足,有研究表明淫羊藿苷对甲状腺功能减退引起的垂体激素分泌不足有确切疗效,但其作用机制还不清楚。目的：探究淫羊藿苷对大鼠甲状腺功能减退后垂体合成分泌激素的影响及机制。方法：(1)40只新生雌性SD大鼠随机分为对照组、模型组及75,150,300 mg/kg淫羊藿苷组,每组8只,后4组给予丙基硫氧嘧啶1.5 mg/(kg·d)灌胃处理构建甲状腺功能减退大鼠模型,各淫羊藿苷剂量组给予75,150,300 mg/kg淫羊藿苷干预治疗,检测各组miR-17-5p、LIM同源框4(LIM homeobox 4,LHX4)、PROP成对同源1蛋白(prop paired end homology 1 protein,PROP1)和HESX1表达,以及垂体合成分泌激素含量。(2)采用锂盐处理共培养的大鼠甲状腺细胞和垂体前叶细胞,给予不同浓度淫羊藿苷(10,30,50,70,100μmol/L)干预,CCK-8试剂盒检测垂体前叶细胞活力;ELISA试剂盒检测促卵泡激素、生长激素和促甲状腺激素水平;实时荧光定量PCR检测miR-17-5p表达;Wester...     

淫羊藿苷通过HIF-1α/VEGF通路介导的血管生成调节大鼠种植窗期子宫内膜容受性

目的 探究淫羊藿苷通过缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子（VEGF）通路介导的血管生成调节大鼠种植窗期子宫内膜容受性的机制。方法 取SD雌性大鼠通过灌胃羟基脲+肾上腺素皮下注射的方法建立子宫内膜容受障碍模型，随机分为模型组、淫羊藿苷低剂量（10 mg/kg）组、淫羊藿苷高剂量（20 mg/kg）组、淫羊藿苷高剂量（20 mg/kg）+空载组、淫羊藿苷高剂量（20 mg/kg）+HIF-1α敲低组，每组20只，另选20只SD雌性大鼠灌胃+皮下注射等剂量生理盐水做对照组，将各组雌鼠与雄鼠合笼得到孕鼠并分组处理后，测定各组大鼠性激素[雌激素（E2）、孕酮激素（P）]水平、平均着床胚胎数；免疫组织化学染色检测各组大鼠子宫内膜微血管密度（MVD）；扫描电子显微镜检测各组大鼠子宫内膜超微结构；免疫组织化学染色和免疫印迹检测各组大鼠子宫内膜组织HIF-1α/VEGF通路蛋白表达。结果 与对照组相比，模型组大鼠子宫内膜表面附着大量短细微绒毛，未发现胞饮突，血清E2与P水平、平均着床胚胎数、子宫内膜MVD、HIF-1α与VEGF蛋白表达明显降低（P<0.05）；与模型组相比，淫羊...     

淫羊藿苷对ConA诱导的小鼠肝脏损伤保护机理的研究

目的:利用刀豆蛋白A(ConA)诱导建立小鼠肝炎模型,观察淫羊藿苷对该损伤模型保护作用的细胞免疫学和分子免疫学机制。方法:采用C57BL/6雄性小鼠,随机分为淫羊藿苷+ConA组、生理盐水+ConA组、淫羊藿苷+生理盐水组。小鼠尾静脉注射ConA,建立T细胞介导的免疫性肝脏损伤模型;采用转氨酶试剂盒测定各组小鼠血液中转氨酶含量;组织病理学观察实验小鼠肝脏组织和肝细胞坏死变化;采用ELISA试剂盒测定血清中炎性细胞因子IFN-γ、TNF-α含量;流式细胞术观察注射ConA后肝脏淋巴细胞的活化变化。结果:与ConA对照组相比,淫羊藿苷干预组小鼠血液中ALT和AST水平明显降低,P<0.01;IFN-γ、TNF-α含量明显降低,P<0.05;H&E染色可见淫羊藿苷干预组小鼠肝细胞核完整,未见炎性细胞的浸润,而ConA对照组小鼠肝细胞核固缩,部分核膜破裂,肝组织内有炎症细胞和红细胞浸润;流式细胞技术发现淫羊藿苷可明显延缓由ConA引起的肝脏NKT细胞的活化,减弱T细胞的浸润。结论:淫羊藿苷对ConA诱导的小鼠肝脏损伤有明显的保护作用,其机理可能与淫羊藿苷降低血液中IFN-γ、TNF-α表达及影响肝脏NKT细胞的活化有关。     

淫羊藿苷对精神分裂症模型大鼠认知及海马组织NRG1/ErbB信号通路的影响

背景:淫羊藿苷是补肾助阳中药淫羊藿的有效活性成分之一,除了可促进生殖系统功能外,还能明显改善精神分裂症,但其具体作用机制仍处于研究与探索阶段。目的:探究淫羊藿苷对精神分裂症大鼠认知功能的影响及机制。方法:采用随机数字表法将48只SD大鼠分4组,每组12只:正常组不造模;模型组、淫羊藿苷低、高剂量组通过腹腔注射N-甲基-D-天冬氨酸受体拮抗剂MK-801(1次/d)诱导精神分裂症模型,连续注射14 d。确认造模成功后,淫羊藿苷低、高剂量组分别灌胃给予25,50 mg/(kg·d)的淫羊藿苷,对照组、模型组灌胃生理盐水,连续给药28 d。给药结束后,进行行为学检测及海马组织尼氏染色和FJB染色、氧化应激水平、炎症因子水平、NRG1/ErbB4信号通路蛋白表达。结果与结论:(1)与模型组比较,给药两组刻板行为评分、自发活动总路程和逃避潜伏期明显减少(P <0.05),穿台次数明显增加(P <0.05);淫羊藿苷高剂量组刻板行为评分、逃避潜伏期(第3-5天)明显低于淫羊藿苷低剂量组(P <0.05);(2)与模型组比较,给药两组海马组织线粒体膜电位、超氧化物歧化酶活性升高(P...     

淫羊藿苷减轻七氟醚诱导的小鼠认知功能障碍

目的 评价淫羊藿苷对七氟醚诱发的术后认知功能障碍(POCD)的影响,探讨其作用机制。方法 将小鼠分为对照组、模型组(七氟醚麻醉+剖腹探查术建立小鼠POCD模型)、淫羊藿苷组、PI3K抑制剂组、淫羊藿苷+抑制剂组、PI3K激活剂组,每组12只。分别采用条件恐惧实验、Y迷宫实验评价小鼠认知功能障碍;ELISA检测血清TNF-α、IL-1β及BDNF水平;取海马组织,尼氏染色观察神经元形态变化;TUNEL染色检测神经元凋亡率;免疫荧光法检测M1型、M2型激活小胶质细胞及其标志物表达水平;Western blot检测TNF-α、IL-1β、IL-10、GSK-3β磷酸化蛋白、Bcl-2表达。结果 与对照组相比,模型组小鼠出现认知功能损伤,海马神经元损伤及凋亡严重,海马组织中小胶质细胞M1型极化介导的促炎反应高于M2型极化介导的抗感染反应,PI3K/Akt-GSK-3β通路及其介导的抗感染及抗凋亡蛋白表达降低(P<0.05)。淫羊藿苷及PI3K激活剂干预处理,均可促进PI3K/Akt-GSK-3β通路及其介导的抗感染及抗凋亡反应,促进海马小胶质细胞M2型极化介导的抗感染反应,缓解海马神经元...     

淫羊藿苷对大鼠肾脏缺血再灌注后炎性损伤的保护

背景：肾移植过程中移植肾缺血再灌注损伤不可避免,采用药物减轻该损伤有助于提高肾移植近远期疗效。淫羊藿苷对心肌和脑缺血的治疗效果较好,对肾脏缺血再灌注的作用尚不清楚。 目的：探索淫羊藿苷对肾脏的缺血再灌注损伤的保护机制。 方法：54只SD大鼠随机等分为假手术组、淫羊藿苷组和模型组,后2组大鼠建立单侧肾脏缺血再灌注损伤模型,假手术组大鼠仅游离肾蒂而不钳夹阻断肾血管。淫羊藿苷组和模型组在造模前2 d至造模后12 d分别给予100 mg/kg淫羊藿苷和1 mL/kg 0.3%羧甲基纤维素钠灌胃,1次/d。 结果与结论：相比于对照组,肾脏缺血再灌注损伤后大鼠血肌酐明显升高,肌酐清除率下降,肾组织出现病理性损伤,而给予淫羊藿苷的大鼠,大鼠肾组织诱生型一氧化氮合酶 mRNA和蛋白表达水平下降,肾组织内的促炎因子(肿瘤坏死因子α、白细胞介素1β,6)、趋化因子(干扰素诱导蛋白10、单核细胞趋化蛋白1、巨噬细胞炎性蛋白2)mRNA的表达水平降低,肾脏缺血再灌注损伤后6 h,大鼠血浆亚硝酸盐/硝酸盐和肾组织内髓过氧化物酶水平最高,而后逐渐下降;且淫羊藿苷组大鼠血浆亚硝酸盐/硝酸盐和肾组织内髓过氧化物酶水平低于模型组(P < 0.05)。提示淫羊藿苷可通过抑制诱生型一氧化氮合酶酶表达及其下游的炎症级联反应而减轻大鼠肾脏缺血再灌注损伤。     

Shear Augmented Dispersion of a Solute in a Casson Fluid Flowing in a Conduit

The unsteady dispersion of a solute in a Casson fluid flowing in a conduit (pipe/channel) is studied using the generalized dispersion model of Gill and Sankarasubramanian. With this approach, the entire dispersion process is described appropriately in terms of a simple diffusion process with the effective diffusion coefficient as a function of time, in addition to its dependence on the yield stress of the fluid. The results are accurate up to a first approximation for small times, but verified with Sharp to be exact for large times. The model brings out mainly the effect of yield stress, or equivalently, the plug flow region on the overall dispersion process. It is found that the rate of dispersion is reduced (i.e., the effective diffusivity decreases) due to the yield stress of the fluid, or equivalently, the plug flow region in the conduit. Also, the effective diffusivity increases with time, but eventually attains its steady state value below a critical time [0.48(a²/D_m) for dispersion in a pipe and 0.55(a²/D_m) for dispersion in a channel—the critical transient time for a Newtonian fluid—where a is the radius of the pipe and D_m is the molecular diffusivity]. At steady state, for dispersion in a pipe with the plug flow radius one tenth of the radius of the pipe, the effective diffusivity is reduced to about 0.78 times of the corresponding value for a Newtonian fluid at equivalent flow rates; for dispersion in a channel, the reduction factor is about 0.73 confirming the earlier result of Sharp. Further, the location of the center of mass of a passive species over a cross section is found to remain unperturbed during the course of dispersion and for different values of the plug flow parameter (i.e., the yield stress of the fluid). The study can be used as a starting first approximate solution for studying the dispersion in the cardiovascular system or blood oxygenators. © 2000 Biomedical Engineering Society. PAC00: 8719Uv, 4760+i, 8350Nj, 8370Hq, 8715Vv, 8710+e, 4755Kf     

Once in a lifetime: a case of a pineal tumour

This paper describes the case of a 14-year-old boy who presented to his general practitioner with a history of headaches and visual problems. Investigations subsequently revealed that he had a pineal tumour. The management of the patient is described and this rare condition discussed.     

Identification of a novel astrovirus in a domestic pig in Hungary

The family Astroviridae consists of two genera, Avastrovirus and Mamastrovirus, whose members are associated with gastroenteritis in avian and mammalian hosts, respectively. We serendipitously identified a novel porcine astrovirus in a fecal specimen from a domestic pig (Sus scrofa domestica) in Hungary. Sequencing of a fragment indicated that it was an ORF1b/ORF2/3′UTR sequence, and it has been submitted to the database as porcine astrovirus type 2 (PAstV-2/Hungary/2007) with accession number GU562296. Its unique sequence characteristics and its phylogenetic position suggest that PAstV-2 could be an important link between previously reported astroviruses and that a genetically divergent lineage of astroviruses exist in piglets.     

Concentration Effects of a Biopolymer in a Microfluidic Device

This paper builds upon our previous effort exploring the behavior of biological macromolecules subjected to a microfluidic flow; here we focus on concentrated solutions of macromolecules. Epifluorescence microscopy and a fluorescent probe were used to visualize -DNA molecules flowing through a silicon-fabricated microfluidic device. The flow path consisted of an inlet reservoir, contracting into a long straight channel, and then expanding into an outlet reservoir. Macromolecules in the flow experienced an elongational flow at the channel contraction along the channel centerline and a shear flow at the channel walls. Previous results on dilute solutions with concentration c = 0.001c ^* indicated that both types of flow can stretch a macromolecule. Generally, stretching increases with the Deborah number (De) and a prolonged exposure to high De may lead to chain scission. In this study, the concentration of -DNA in solution was increased to c = 0.1c ^*, and all other variables were held constant. Although both flow types stretched -DNA molecules, the deformation in the more concentrated solution was less than that in dilute solution. Furthermore, in contrast to dilute solution at the same or slightly higher De, no evidence of molecular degradation was observed as the macromolecules traveled through the channel. These findings are relevent when designing microfluidic systems for conducting biochemical analyses.     

Identification of a chemotactic sensitivity in a coupled system

Email: renee.fister{at}murraystate.edu Corresponding author. Email: maeve.mccarthy{at}murraystate.edu Received on July 16, 2007. Revised on March 24, 2008. Accepted on June 7, 2008. Chemotaxis is the process by which cells behave in a way thatfollows the chemical gradient. Applications to bacteria growth,tissue inflammation and vascular tumours provide a focus onoptimization strategies. Experiments can characterize the formof possible chemotactic sensitivities. This paper addressesthe recovery of the chemotactic sensitivity from these experimentswhile allowing for non-linear dependence of the parameter onthe state variables. The existence of solutions to the forwardproblem is analysed. The identification of a chemotactic parameteris determined by inverse problem techniques. Tikhonov regularizationis investigated and appropriate convergence results are obtained.Numerical results of concentration-dependent chemotactic termsare explored.