ApoE-/-小鼠颈动脉稳定性粥样硬化模型的建立及7.0TMR动态观察

目的 建立ApoE-/-小鼠颈动脉稳定性动脉粥样硬化(AS)模型,并探讨用高场强7.0T小动物MR检测AS的形成过程.方法 对10只ApoE-/-小鼠损伤并阻断一侧颈总动脉血流20 min,之后高脂饮食饲养7周,分别在术后4、7周进行7.0T MR检测与病理学检查.结果 4周后MRI显示患侧均出现不同程度的血管壁高信号,7周后MRI表现为损伤血管高壁信号区增厚并管腔狭窄、不规则,创伤后血管腔面积呈下降趋势.对应病理学检查显示,4周后颈总动脉腔内斑块形成,斑块内泡沫细胞及脂质坏死核心形成,其上覆盖厚纤维帽;7周后斑块内增生的内膜内见广泛钙质沉积.结论 用损伤及高脂饮食方法可成功建立ApoE-/-小鼠稳定期AS模型;高场强7.0T MR可成功检测小鼠颈动脉稳定期粥样硬化的形成过程,进一步研究ApoE-/-小鼠易损斑块提供研究基础.     

血管紧张素Ⅱ快速诱导ApoE-/-小鼠腹主动脉夹层动脉瘤模型的建立及其MR成像

目的 建立ApoE-/-小鼠腹主动脉夹层动脉瘤模型,探讨超高场强7.0T MR检测ApoE-/-小鼠腹主动脉瘤的价值. 方法 10月龄ApoE-/-小鼠饲以高脂饮食10周后,背部埋置血管紧张素Ⅱ缓释泵,Ang Ⅱ分为1000 ng/(kg·min)和500 ng/(kg·min)组,对照组埋置生理盐水,装泵前及装泵后14天内行MR活体扫描,扫描后取腹主动脉行病理学检查. 结果 Ang Ⅱ灌注高剂量组第6或第7天即形成夹层动脉瘤,T2WI示一侧管壁周可见新月形超高信号,病理证实为中膜与外膜间出血;低剂量组第13、14天后也见腹主动脉夹层动脉瘤形成,MR示管壁信号于T2WI及PDWI均明显增加,并可见斑点状高信号向腔外突出,与病理内膜断裂血流冲击中膜形成主动脉夹层一致. 结论用2种剂量的血管紧张素Ⅱ灌注2周内均可成功建立ApoE-/-小鼠腹主动脉夹层动脉瘤模型,前组可在更短时间内建模成功.超高场强MR可成功用于活体检测腹主动脉夹层动脉瘤形成.     

超声生物显微镜成像对载脂蛋白E基因敲除小鼠早期动脉粥样硬化的分析

目的 利用超声生物显微镜（UBM）成像分析载脂蛋白E基因敲除（ApoE-/-）小鼠主动脉早期动脉粥样硬化（AS）的超声特征.方法 8周龄和16周龄雄性ApoE-/-小鼠各8只为实验组,同周龄的雄性C57BL/6小鼠各8只为对照组.使用UBM观察小鼠主动脉根部、升主动脉和主动脉弓的形态结构,并于主动脉根部短轴切面测量内-中膜厚度（IMT）.检查后处死小鼠取标本,行病理学检查.结果 ApoE-/-小鼠的主动脉根部IMT较同周龄对照组增厚,差异有统计学意义（P〈0.01）;16周龄ApoE-/-小鼠较8周龄ApoE-/-小鼠主动脉根部IMT增厚更为明显,差异有统计学意义（P〈0.01）.形态学病理检查显示6只16周龄ApoE-/-小鼠主动脉根部、升主动脉小弯侧及无名动脉可见局部管壁增厚,有散在白色脂纹形成.结论 UBM成像可无创观察活体ApoE-/-小鼠升主动脉早期AS的病变特征,能有效监测ApoE-/-小鼠AS病变的进程.     

超微超顺磁性氧化铁对兔动脉粥样硬化斑块的MRI研究

目的:利用超微超顺磁性氧化铁(USPIO)对兔动脉粥样硬化斑块进行磁共振成像,分析其磁共振表现特点及其价值.方法:实验组以球囊导管损伤腹主动脉内膜+高脂饮食的方法建立兔动脉粥样硬化模型12只,对照组3只行假手术和普通饲料喂饲.12周后对所有动物行USPIO增强前后的腹主动脉磁共振扫描,连续跟踪扫描6d(每隔24h 1次),在T2WI序列上观察血管壁信号变化情况,比较管壁信号噪声比(SNR),并将磁共振结果与病理学相对照.结果:USPIO增强后显示实验组在T2WI序列上腹主动脉管壁信号逐渐降低,在第4天SNR值达到最低点,较增强前信号差异有统计学意义(P＜0.05),而对照组腹主动脉在增强前后管壁信号无变化.病理证实所有动物模型兔腹主动脉都发生动脉粥样硬化病变,注射USPIO后处死的实验组兔普鲁士蓝染色为阳性,电镜显示USPIO颗粒存在于巨噬细胞胞浆的细胞器内.对照组兔腹主动脉病理检查为阴性.结论:USPIO颗粒可以被兔动脉粥样硬化斑块中的巨噬细胞特异性吞噬并引起相应的磁共振信号改变,USPIO磁共振成像有望在体观测动脉粥样硬化斑块内的炎症反应.     

3.0T MRI观察兔腹主动脉粥样硬化斑块演变过程

目的 探讨MRI在识别兔动脉粥样硬化斑块中的诊断价值.方法 20只新西兰白兔,随机设置实验组16只,对照组4只,结合球囊拉伤腹主动脉和间断高脂饲料喂养,建立动脉粥样硬化模型;在建模后2、3、4个月分别行高分辨MR成像.通过测量腹主动脉管壁厚度和面积、管腔面积、管壁信号增强程度等指标,观察腹主动脉壁的重构过程,并对模型最终的斑块成分进行MRI和组织病理结果对照研究.结果 对17只兔(实验组14只,对照组3只)完成3次MR检查,并获得组织病理学结果.MRI显示,实验组腹主动脉管壁厚度和面积逐渐增厚,且与同期对照组相比差异均有统计学意义(P＜0.01);实验组腹主动脉管腔进行性扩张,管壁强化程度较对照组增加明显,但演变过程不明显.另外,MRI对兔腹主动脉硬化斑块的成分判别限制在纤维、脂质和钙化斑块,对纤维斑块、脂质斑块识别率较高.结论 高分辨MRI可以无创性地观察动脉粥样硬化动物模型腹主动脉管壁重构的演变过程,有助于对动脉硬化斑块的预后和药物干预进行探索.     

FIZZ1与动脉粥样硬化关系探讨

目的 探讨FIZZ1在ApoE基因敲除鼠粥样斑块表达情况并探讨其可能的表达细胞.方法 C57BL/6J ApoE基因敲除鼠及C57BL/6J野生型小鼠各9只,分别喂食高脂饲料及普通饲料,24周后处死小鼠,自主动脉根部至腹主动脉离断整个血管,石蜡包埋后作连续切片,行HE染色及FIZZ1免疫组化.检测血管斑块内FIZZ1表达情况,体外模拟粥样斑块内Th2型细胞因子环境,检测斑块内FIZZ1表达是否与Th2型细胞因子刺激平滑肌细胞或巨噬细胞有关.结果 免疫组化可见FIZZ1在粥样硬化斑块内明显表达,Th2型细胞因子可以刺激巨噬细胞FIZZ1表达,但不能刺激平滑肌细胞FIZZ1表达.结论 正常血管壁内未见FIZZ1表达,ApoE基因敲除鼠粥样斑块表达FIZZ1,动脉粥样硬化斑块内Th2型细胞因子刺激巨噬细胞可能为FIZZ1表达机理之一.     

瑞舒伐他汀和阿司匹林对兔腹主动脉粥样硬化斑块疗效的磁共振研究

目的应用磁共振成像评价瑞舒伐他汀、阿司匹林以及二者联合用药对兔动脉粥样硬化斑块的疗效,并探讨其对炎症细胞的抑制作用。方法 160只新西兰兔行高脂饮食联合腹主动脉内膜损伤术,诱导动脉粥样硬化斑块的发生。所有动物随机分成对照组(高脂饮食)、A组(高脂饮食+阿司匹林)、T组(高脂饮食+瑞舒伐他汀)和AT组(高脂饮食+阿司匹林+瑞舒伐他汀),每组各40只;每组动物又随机分成1周组、2周组、1个月组和2个月组,每组各10只。分别于相应时间点行腹主动脉MR检查,分析斑块负荷即管壁标准化指数(NWI)的变化。MR检查后立即处死动物,尸检取得腹主动脉标本,行HE染色和巨噬细胞免疫组化染色,分析腹主动脉斑块形态学、斑块巨噬细胞含量的变化。结果 A组、T组和AT组NWI在各时间点均较对照组减低(1周、1个月及2个月时,P0.05)。随时间延长对照组动脉内膜逐渐增厚;在各时间点A组、T组和AT组动脉内膜增厚程度均较对照组减轻。在2个月时,A组、T组和AT组的巨噬细胞含量较对照组减少。结论瑞舒伐他汀、阿司匹林和两药联合均能抑制斑块进展,减轻斑块内炎症反应;高分辨MRI可用于对药物治疗效果的评估。     

靶向Rho激酶1纳米探针联合MRI可视化动脉粥样硬化斑块的实验研究

目的 评估Rho激酶(Rho-kinase, ROCK)1在动脉粥样硬化(atherosclerosis, AS)斑块中的表达,合成ROCK1靶向探针,并探索其可视化AS斑块的可行性。材料与方法 ROCK1抗体与超小超顺磁性氧化铁纳米颗粒偶联制备靶向探针(Fe₃O₄@PEG-ROCK1)并表征。高脂喂养载脂蛋白E基因敲除(Apolipoprotein-Edeficient, ApoE^-/-)小鼠,在10、16、22、28、34周随机取小鼠(n=5)测量体质量。主动脉免疫染色切片及蛋白印迹实验观察ROCK1的表达及活性。将34周ApoE^-/-小鼠分成两组,一组尾静脉注射Fe₃O₄@PEG(n=10),一组尾静脉注射Fe₃O₄@PEG-ROCK1(n=10),注射探针前及注射后8、16 h进行MRI。Image J软件计算斑块信号。病理分析腹主动脉标本。结果 Fe₃O₄@P...     

巨噬细胞MRI检测兔早期腹主动脉粥样硬化斑块

目的 观察巨噬细胞MRI在检测兔早期动脉粥样硬化斑块中的应用价值。方法 将10只健康新西兰兔随机均分为模型组及对照组,对模型组通过球囊拉伤联合高脂饲料建立腹主动脉粥样硬化模型,对照组不予任何干预。对两组动物行MR扫描,检测静脉注射葡聚糖四氧化三铁纳米颗粒（DCIONP）对比剂前及注射后45 min、24 h、48 h、72 h、96 h和120 h 血管壁信号强度（SI）及信号强度变化值（ΔSI）。之后处死动物,病理观察动脉粥样硬化斑块。结果 模型组斑块注射DCIONP后45 min SI升至最高,48 h开始低于注射前水平,96 h降至最低;对照组管壁于注射DCIONP后45 min均匀强化,24 h后SI基本恢复至注射前水平,其后SI无明显变化。两组间各时间点ΔSI差异均有统计学意义（P均<0.05）。病理结果表明血管壁信号衰减区与斑块内铁蓝染区及巨噬细胞分布相符。结论 巨噬细胞MRI可检测兔早期动脉粥样硬化斑块,可能具有潜在临床应用价值。     

兔动脉粥样硬化斑块巨噬细胞表达动态变化

目的:检测巨噬细胞在兔动脉粥样硬化模型斑块中表达的动态变化。方法:24只健康雄性新西兰大耳白兔随机分为试验组(15只)和对照组(9只),试验组在球囊损伤腹主动脉内膜后喂养高脂饮食,对照组喂养普通饲料,于6,12,18周分别处死动物,分离腹主动脉,检测脂质和脂蛋白,应用光学显微镜观察动脉粥样硬化进程,采用免疫组织化学方法分析巨噬细胞在斑块处的表达及定位。结果:高脂饮食喂养后6周,兔动脉内皮受损,12周和18周可见明显动脉粥样硬化斑块形成。与对照组比较,巨噬细胞在动脉粥样硬化斑块处表达增高,主要位于内膜斑块的中下部分;巨噬细胞表达量随着动脉粥样硬化斑块的进展而增多。结论:巨噬细胞的表达随着斑块进展而增多,可能与动脉粥样硬化进展及斑块不稳定相关。     

影响NOD/SCID小鼠淋巴瘤18F-FDG PET摄取的免疫因素分析

目的 通过比较两种不同类型免疫缺陷动物肿瘤组织的18F-FDG标准摄取值(SUV),初步探讨B、NK细胞免疫与肿瘤组织的相互作用.方法 对NOD/SCID小鼠(T、B、NK免疫联合缺陷)12只,BALB/C裸鼠(无T细胞免疫)12只,分别种植淋巴瘤细胞(A20),成瘤后对各组均经尾静脉注射18F-FDG 8.32～12.02 MBq(225～325 μCi),使用Philips小动物PET进行全身动态和静态扫描,观察B细胞免疫和NK细胞自然杀伤免疫对肿瘤组织摄取18F-FDG的影响,并分析免疫因素在肿瘤摄取18 F-FDG中的作用.结果 NOD/SCID小鼠最大SUV(SUVmax)为18.33±3.42,高于BALB/C裸鼠[(9.66±4.15),t=4.981,P＜0.01],平均SUV(SUVmean)为11.04±1.40,高于BALB/C裸鼠[(5.47±3.30),t=4.718,P=0.001].结论 不同免疫状态对小鼠淋巴瘤的18F-FDG摄取水平存在影响.     

18F-氟乙酸可否辅助18F-FDG用于胰腺癌的PET/CT显像?

目的 探讨18F-氟乙酸(11F-FAC)是否适用于胰腺癌原发灶的探测.方法 观察正常雄性SD大鼠注射18F-FAC后20 min,1 h、2 h和3 h的生物分布,再比较荷胰腺癌稞鼠18F-FAC与18F-FDG的生物分布差异,最后用PET/CT显像比较两种示踪剂在松节油所致大鼠炎症模型中的放射性摄取.结果 正常胰腺18F-FAC分布较少,1 h清除最明显[(0.24±0.07)％ID/g,P=0.002].荷瘤模型对18F-FAC和18F-FDG两种示踪剂均有较高的放射性摄取,分别为(5.12±2.11)和(3.52±0.23)％ID/g,且靶本比几乎相同,分别为(2.81±1.00)和(2.85±0.37).炎症显像提示,建模后第5、7天18F-FDG显像的炎症/肌肉比值高于18F-FAC(P均＜0.001).结论 18F-FAC可能成为PET/CT探测胰腺癌的一种选择,并能在炎症鉴别诊断中发挥一定的作用.     

Immunoglobulin treatment reduces atherosclerosis in apo E knockout mice.

Atherosclerosis is associated with immune activation. T cells and macrophages infiltrate atherosclerotic plaques and disease progression is associated with formation of autoantibodies to oxidized lipoproteins. In the apo E knockout mouse, a genetic model of cholesterol-induced atherosclerosis, congenital deficiency of macrophages, lymphocytes, or interferon-gamma receptors result in reduced lesion formation. We have now evaluated whether immune modulation in the adult animal affects disease development. Injections of 7-wk-old male apo E knockout mice with polyclonal immunoglobulin preparations (ivIg) during a 5-d period reduced fatty streak formation over a 2-mo period on cholesterol diet by 35%. Fibrofatty lesions induced by diet treatment for 4 mo were reduced by 50% in mice receiving ivIg after 2 mo on the diet. ivIg treatment also reduced IgM antibodies to oxidized LDL and led to inactivation of spleen and lymph node T cells. These data indicate that ivIg inhibits atherosclerosis, that it is effective both during the fatty streak and plaque phases, and that it may act by modulating T cell activity and/or antibody production. Therefore, immunomodulation may be an effective way to prevent and/or treat atherosclerosis.     

Apolipoprotein E deficiency in mice: gene replacement and prevention of atherosclerosis using adenovirus vectors.

Apolipoprotein E (apoE)-deficient mice develop marked hyperlipidemia as well as atherosclerosis and thus are an excellent animal model for evaluating the potential for gene therapy in human genetic dyslipoproteinemias. Recombinant adenovirus containing either human apoE (rAdv.apoE) or the reporter gene luciferase (rAdv.luc) were generated and infused intravenously in apoE-deficient mice with preinfusion plasma total cholesterol of 644 +/- 149 mg/dl an cholesterol rich VLDL/IDL. After a single infusion of rAdv.apoE, plasma concentrations of human apoE ranging from 1.5 to 650 mg/dl were achieved. Adenovirus-mediated apoE replacement resulted in normalization of the lipid and lipoprotein profile with markedly decreased total cholesterol (103 +/- 18mg/dl), VLDL, IDL, and LDL, as well as increased HDL. Measurement of aortic atherosclerosis 1 mo after adenoviral infusion demonstrated a marked reduction in the mean lesion area of mice infused with rAdv.apoE (58 +/- 8 x 10(3) microns2) when compared with control mice infused with rAdv.luc (161 +/- 10 x 10(3) microns2; P < 0.0001). Thus, apoE expression for 4 wk was sufficient to markedly reduce atherosclerosis, demonstrating the feasibility of gene therapy for correction of genetic hyperlipidemias resulting in atherosclerosis. The combined use of adenovirus vectors and the apoE-deficient mouse represents a new in vivo approach that will permit rapid screening of candidate genes for the prevention of atherosclerosis.     

Insulin attenuates the cytokine response in a burn wound infection model

A massive burn is one of the most serious injuries resulting in major imbalances of the immune system. The aftermath of a burn is frequently complicated by infections and septic events that additionally increase mortality and morbidity.The aim of the present study was to investigate if insulin attenuates the cytokine response of burned mice challenged with Pseudomonas. Male mice (C57/BL/6) received a full thickness burn of 35% of their total body surface area. Mice received 5 IU/kg insulin i.p. or an equal volume of saline for 5 days after burn. Mice were challenged with 5x10 colony forming units Pseudomonas aeruginosa intraperitoneally. Serum was harvested 6 h after the bacterial challenge, and 18 serum cytokines were measured using the Bio-Plex suspension array system (Bio-Rad, Hercules, Calif). All 18 cytokines were elevated after the Pseudomonas challenge. However, mice treated with insulin showed significantly lower proinflammatory cytokine concentrations of interleukin 5, interleukin 6, and keratinocyte-derived chemokine after the Pseudomonas infection when compared with placebo-treated mice (P<0.05). In contrast, serum concentrations of G-CSF were significantly higher in insulin-treated animals when compared with placebo (P<0.05). We conclude, that insulin treatment selectively modulates specific cytokines in a burn wound infection model.     

受鼠年龄对小鼠异基因骨髓移植后急性移植物抗宿主病发生的影响

本研究通过建立2种周龄的小鼠急性移植物抗宿主病(aGVHD)模型,探讨受鼠年龄对小鼠异基因骨髓移植后aGVHD发生的影响。选用近交系8-10周龄C57BL/6(H-2Kb)小鼠作为供鼠,18-20周龄及8-10周龄的BALB/c(H-2Kd)小鼠作为受鼠;两种周龄的小鼠均分为正常对照组、单纯照射组和模型组。单纯照射组及模型组小鼠给予总剂量率为7.5 Gy的60Coγ射线全身照射,其剂量率为0.68 Gy/min。模型组小鼠照射后4 h进行骨髓细胞+脾细胞移植,每只小鼠输入骨髓细胞数5×106个,脾细胞数5×105个。每天观察各组小鼠的一般情况、生存状态。于照射后第5、10、15、20、25、30天计数各组小鼠外周血白细胞数量;采用流式细胞术测定各组小鼠外周血白细胞嵌合率及T淋巴细胞亚群、Th1细胞比例;观察正常对照组、单纯照射组及第5、15和25天模型组小鼠肝脏、小肠和皮肤的组织病理学变化。结果表明:照射后1个月模型组小鼠均发生aGVHD,18-20周龄组小鼠与8-10周龄组相比,移植后aGVHD发生率低(60%vs 100%),临床评分低,生存率比为83%vs 61%,两组间差异显著;18-20周龄组小鼠外周血白细胞在移植后第10天达到清髓,第15天白细胞开始恢复,而8-10周龄组则分别为移植后第5和第10天,两组间差异显著;18-20周龄组小鼠外周血供者来源的白细胞在移植后第20天达到完全嵌合,而8-10周龄组为第10天,两组间差异显著;18-20周龄组小鼠外周血T淋巴细胞亚群中CD8+T细胞及Th1细胞比例均低于8-10周龄组,两组间差异显著。组织病理学变化显示,在相同时间点,18-20周龄组小鼠的肝脏、小肠及皮肤的炎症和坏死程度均较8-10周龄组轻微。结论:18-20周龄受鼠比8-10周龄受鼠aGVHD发生率低,程度轻,生存状况较好,受鼠年龄影响aGVHD的发生和进程。     

Role of interleukin 18 in nitric oxide production and pancreatic damage during acute pancreatitis

The release of the immunomodulator, interleukin 18 (IL-18) into sera early in acute pancreatitis (AP) corresponds to disease severity. IL-18 induces nitric oxide (NO), which is involved in the pathophysiology of pancreatitis. The objective of this study was to clarify the role of IL-18 in pathogenesis and NO production during early AP using recombinant mouse (rm) IL-18 protein and IL-18 gene knockout (KO) mice. After pretreatment with phosphate-buffered saline or rmIL-18, wild-type (WT) or KO mice were injected intraperitoneally with phosphate-buffered saline (sham) or cerulein (AP) hourly for 3 h. Blood, pancreas, spleen, and liver were collected until 24 h after the first dose. Main outcome measures were serum IL-18, amylase and lipase levels, histological evaluation of the pancreas with parenchyma vacuolization of acinar cells, mRNA expression of inducible NO synthase (iNOS) in the pancreas, and spleen, liver, and plasma NO metabolite level. Serum IL-18 was significantly increased immediately after induction of AP in WT mice. Serum amylase, lipase, and the numbers of acinar cells with parenchyma vacuolization were significantly higher in the group AP/KO than in the group AP/WT, but these parameters were improved by dose-dependent pretreatment with rmIL-18 administration in both groups. Pancreatic iNOS gene expression and plasma NO metabolites were significantly increased by 6 h after the initiation of AP, but were significantly lower in the group AP/KO than in the AP/WT mice. Pretreatment with rmIL-18 also significantly increased these levels in both groups. Splenic and hepatic iNOS expression was not changed after the initiation of AP in WT mice, whereas pretreatment with rmIL-18 also increased these levels. Administration of aminoguanidine, a selective iNOS inhibitor, before AP induction abolished the protective effect of pretreatment with rmIL-18 on pancreatic injury. IL-18 appears to protect the pancreas during early induced-induced AP in mice, probably through induction of NO release from an iNOS source. IL-18 may be a target for new AP therapeutics.     

转录因子EN1在帕金森病模型小鼠中脑表达中的变化

目的:研究小鼠帕金森病(PD)模型急性期中脑转录因子EN1表达变化的特点及小鼠的自发性活动改变。方法:应用6-羟多巴胺(6-OHDA)纹状体注射制备小鼠PD模型;旷场试验观察其行为学变化;免疫组织化学/荧光染色检测注药后24h内中脑EN1、酪氨酸羟化酶(TH)的表达变化。结果:与对照组相比,模型组运动方式明显异常,7d内基本恢复正常;运动总量随注药后时间延长呈恢复趋势,但与对照组对比无显著差异;中央区域活动时间逐渐减少,反映了焦虑指数增高。与对照侧相比,实验侧中脑EN1免疫阳性细胞数在3—9h时已出现减少,12—18h时已较显著,18h为65.2±22.3%(P<0.05),21h时减少非常显著。TH阳性的多巴胺能(DA)神经元数目也随时间逐渐减少,但时间上略晚于EN1,15h才可见减少,18h时减少明显,为68.3±1.2%(P<0.05)。EN1在中脑主要定位于细胞核,但也可见于细胞浆。结论:注射6-OHDA后,小鼠出现行为学改变,焦虑指数增高;实验侧中脑EN1和TH阳性细胞数均随时间逐渐减少且EN1变化早于TH,提示转录因子EN1的减少可能是诱导DA神经元凋亡及PD部分症状出现的重要原因。     

Pterostilbene,a novel natural plant conduct,inhibits high fat-induced atherosclerosis inflammation via NF-κB signaling pathway in Toll-like receptor 5 (TLR5) deficient mice

Atherosclerosis is a specific form of an artery wall thickens, a syndrome affecting arterial blood vessels due to a chronic inflammatory response in the walls of arteries, which is promoted by fat accumulation. Toll-like receptors (TLRs) play prominent roles in inflammatory responses. And TLR5 is overexpressed in several diseases. Here in our study, we investigated the effect of TLR5 in high fat-induced atherosclerosis via NF-κB signaling pathway modulating pro-inflammatory cytokines releasing. Our results found that high fat induced atherosclerosis in wild type mice with fat accumulation and inflammatory response through NF-κB activation. Contrastly, TLR5 knockout mice displayed lower fat accumulation and ameliorated inflammation after high fat feeding with NF-κB inactivation. In addition, pterostilbene, as a natural dimethyl ether derivative of resveratrol mainly from blueberries, has diverse pharmacological activities, especially anti-inflammation. Our study also found that pterostilbene displayed inhibited role in suppressing inflammatory response through inactivating NF-κB signaling pathway regulated by TLR5 down-regulation in high fat-induced mice. Moreover, in vitro experiments of vascular smooth muscle cells (VSMCs) challenged with LPS or TNF-α, further indicated that NF-κB was involved in atherosclerosis progression, leading to high secretion of pro-inflammatory cytokines. However, VSMCs from TLR5 deficient mice inhibited phosphorylated levels of NF-κB signalilng pathway, finally resulting in down-regulation of inflammatory cytokines. Notably, pterostilbene also displayed suppressed role in inflammatory response via NF-κB inactivity in LPS or TNF-α-induced VSMCs by decreasing TLR5 expression. The results above indicated a novel therapeutic strategy of pterostilbene to protect against atherosclerosis via TLR5 regulation for clinic treatment in the future.     

Antiviral Activity of BL-3849A, a Low-Molecular-Weight Oral Interferon Inducer

Oral administration of BL-3849A to adult mice resulted in peak serum interferon titers of 4,000 units from 15 to 30 h after administration, with detectable levels persisting until 48 h. After intraperitoneal (i.p.) inoculation, peak serum interferon titers of 1,000 to 3,000 units were noted between 9 and 18 h. Multiple injections of the inducer by either route resulted in a marked decrease in the interferon response with each successive dose. In mice infected intranasally with the Rochester mouse virus strain of encephalomyocarditis virus, oral treatment with BL-3849A reduced mortality when initiated either 18 h before or 1 h after infection. In contrast, administration of drug by the i.p. route decreased mortality only if begun before infection. In mice inoculated i.p. with encephalomyocarditis virus, treatment by both the oral and the i.p. route decreased the mortality whether initiated 18 h before or 1 h after infection. Treatment by the oral, but not the i.p., route reduced mortality of mice inoculated i.p. with Semliki forest virus or Herpesvirus hominis type 2. BL-3849A appeared to be as effective as tilorone hydrochloride, but less effective than polyriboinosinic-polyribocytidylic acid, in the treatment of these viral infections of mice.