活络祛痹贴膏抗炎镇痛作用及其机制研究

目的:探讨活络祛痹贴膏的抗炎镇痛作用及其机制研究,为其在临床中应用提供实验依据.方法:采用小鼠热板法、小鼠耳肿胀法、大鼠足肿胀法,贴敷给药7天,考察小鼠镇痛抗炎作用,采用Elisa测定足肿胀大鼠血清中白介素-6(IL-6)和抗肿瘤坏死因子(TNF-α)的表达水平.结果:活络祛痹贴膏高剂量组(10g·kg-1)可显著提高热板法小鼠痛阈值,显著减轻小鼠的耳肿胀度和大鼠足肿胀度(P＜0.05).活络祛痹贴膏中剂量组(7.5g·kg-1)可显著降低大鼠血清中IL-6和TNF-α的表达水平(P＜0.05).结论:活络祛痹贴膏具有抗炎、镇痛作用,可能通过影响血清中IL-6和TNF-α含量来实现.     

科学家再生感音毛细胞恢复小鼠听力

据报道,美国马萨诸赛州眼耳医院和哈佛医学院研究人员首次证明,用一种药物刺激成年小鼠耳蜗里残余的毛细胞,能使其再生出新的毛细胞,从而部分恢复小鼠因噪音而受损的听力。这一成果在耳聋治疗应用上有着光明前景,有望帮助聋人恢复听力。 研究人员先通过试管实验选出了一种叫做伽玛一分泌物抑制剂的药物,这种药会抑制一种叫做Notch蛋白产生的信号,Notch蛋白位于围绕着毛细胞的支持细胞表面,     

苯对小鼠嗜多染微核的影响

研究观察苯对小鼠骨髓嗜多染红细胞微核的影响,对苯的遗传毒性进行评价。将小鼠随机分为阴性对照组、阳性对照组及低浓度、中浓度、高浓度、3个剂量共5组,每组10只,雌雄各半,采用静式吸入染毒法,3个剂量组每天染毒1次。连续30d。2个对照组放置在另一个染毒柜中,除不染毒外其余处理均同染毒组。阳性对照组小鼠于处死前1d腹腔注射环磷酰胺(60mg/kg/B·W)1次。30d后处死小鼠,采用常规微核实验方法,检测小鼠骨髓嗜多染红细胞微核。以微核率为指标,进行方差分析,判断苯对小鼠骨髓嗜多染红细胞微核的影响。实验组组的微核率要高于阴性和阳性对照组,高剂量组的微核率最高!实验中的苯试剂可促进小鼠骨髓嗜多染红细胞产生微核,具有遗传毒性,且高浓度的苯毒性最强。     

碘酸钾和碘化钾对大鼠肝脏SIRT1 mRNA表达的影响

目的:观察不同剂量的碘酸钾和碘化钾对大鼠肝脏SIRT1基因表达的影响。方法:根据喂养碘剂和剂量不同将Wistar大鼠随机分为8组,即:适碘组(KI、KIO3),10倍高碘组(10KI、10KIO3)、50倍高碘组(50KI、50KIO3),100倍高碘组(100KI、100KIO3)。喂养半年后,利用实时荧光定量PCR(Real-time PCR)分析大鼠肝脏SIRT1基因表达水平。结果:适碘组中,SIRT1在KI组中的mRNA表达量高于KIO3组,P<0.05;10倍剂量组中,SIRT1在10KI组中的基因表达水平明显高于10KIO3,P<0.01;50倍和100倍剂量组中,SIRT1的基因表达量在两种不同碘剂组中没有统计学差异,P>0.05;不论摄入何种碘剂,SIRT1在高剂量碘组中的基因表达量均高于适碘组。结论:高剂量的碘化剂和碘酸钾均可上调大鼠肝脏SIRT1基因表达量,肝脏SIRT1基因的表达上调可能是机体改善高碘致高脂血症的一种重要的分子机制。     

猫爪草多糖抗炎作用机制的实验研究

目的:考察不同浓度猫爪草多糖(PRRT)对早、中、晚期炎症模型的影响,探索其抗炎机制方法:将小鼠和大鼠随机各分为阴性对照组和阳性对照组和PRRT低、中、高剂量组,每组10只。采用二甲苯致耳廓肿胀、醋酸诱发小鼠腹腔毛细血管通透性增高,蛋清致大鼠背部气囊滑膜炎、棉球诱发小鼠肉芽肿,探讨PRRT的抗炎作用。称体质量测定各组小鼠耳的炎症肿胀程度及肉芽增生水平,用化学方法检测各组小鼠腹腔洗涤液中的伊文思蓝含量、滑膜炎渗出液容积、渗出液中的白细胞(WBC)计数和肿瘤坏死因子(TNF)-a含量,渗出液和血清中超氧化物歧化酶(S0D)、丙二醛(MDA)含量。结果:PRRT组分的高剂量组与阴性对照组相比,可显著抑制小鼠耳肿胀、降低毛细血管通透性及肉芽组织增生。结论:PRRT能够缓解早、中、晚期炎症形成,其抗炎机制可能是PRRT可降低血清和滑膜炎渗出液中的MDA含量,提高SOD活性,进而减轻脂质过氧化损伤。     

伯氏螺旋体在小鼠宿主中的关节特异性转录谱

目的建立伯氏疏螺旋体感染的小鼠模型,研究伯氏疏螺旋体在小鼠关节组织中的关节特异性基因表达谱。方法首先,建立伯氏疏螺旋体感染小鼠模型,在不同时间点处死小鼠,收集小鼠关节、心脏、皮肤和膀胱组织,从四种组织中分别提取总RNA;随后,用DECAL技术和微阵列技术分析不同时间点伯氏疏螺旋体在四种组织中的转录组;最后,将伯氏疏螺旋体在关节中的转录组依次与其他三种组织中的转录组进行比较,找出仅在关节中表达的伯氏疏螺旋体基因,从而获得伯氏疏螺旋体不同时间点的关节特异性基因表达谱。结果与其他组织相比,在感染后第15天,伯氏疏螺旋体在小鼠关节组织特异地表达21个基因,其中13个基因位于伯氏疏螺旋体染色体上,8个基因位于质粒上;在感染后的第105天,伯氏疏螺旋体在小鼠关节组织特异地表达24个基因,其中13个基因位于伯氏疏螺旋体染色体上,11个基因位于质粒上。结论伯氏疏螺旋体在小鼠关节组织中存在独特的基因表达谱,这些在关节中特异表达的基因可能与莱姆关节炎的发生、发展有关。     

壮药依山红对四氯化碳所致急性肝损小鼠保肝作用研究

观察壮药依山红醇提物、水提物的毒性及对四氯化碳（CCl4）所致小鼠急性肝损伤的作用。采用常规小鼠急性毒性试验方法;CCl4腹腔注射造成急性肝损伤模型,将小鼠随机分成空白对照组、模型组、联苯双酯阳性药组和依山红水提物组、醇提物组,观察各剂量组对小鼠血清谷丙转氨酶（GPT）及谷草转氨酶（GOT）的影响。壮药依山红水提物（Y1）、醇提物（Y2）的最大耐受量分别为301 g/kg、304g/kg。联苯双酯模型组及依山红醇提取物各剂量组与模型组相比均有显著性差异。依山红对于CCl4所致小鼠急性肝损伤具有一定的保肝降酶作用,且醇提物优于水提物。     

氯化铵对顺铂诱导A549细胞凋亡的形态学研究

目的探讨氯化铵(NH4CL)对顺铂(cisplatin,CDDP)抑制A549细胞增殖的影响。方法体外培养人肺癌A549细胞,MTT法检测NH4CL及CDDP对人肺癌A549细胞增殖率的影响;光镜下观察NH4CL及CDDP对A549细胞生长的影响;共聚焦显微镜下观察A549细胞核的形态变化。结果与对照组相比,给予不同浓度的NH4CL及CDDP导致A549细胞增殖率明显下降;光镜下观察A549细胞经非毒性剂量的NH4CL与CDDP联合应用处理后细胞生长抑制明显高于单独给予CDDP组;共聚焦显微镜观察可见非毒性剂量的NH4CL与CDDP联合应用处理A549细胞核碎裂现象明显多于单独CDDP处理组。结论 NH4CL可以促进CDDP对A549A细胞的凋亡诱导作用。     

四氧嘧啶致小鼠、大鼠糖尿病模型研究

目的:研究四氧嘧啶尾静脉注射小鼠和大鼠诱导糖尿病模型,观察不同剂量四氧嘧啶诱导糖尿病模型的稳定性.方法1分别对小鼠尾静脉注射四氧嘧啶60、70、80mg/kg和对大鼠尾静脉注射四氧嘧啶30、40、50mg/kg,测定不同时点小鼠和大鼠的血糖值及体重.结果60、70和80mg/kg四氧嘧啶剂量均可导致小鼠糖尿病模型,但70和80mg/kg剂量组小鼠死亡率较大,而60mg/kg组小鼠糖尿病模型稳定;30mg/kg四氧嘧啶剂量不能造成大鼠糖尿病模型,40和50mg/kg四氧嘧啶剂量均可导致大鼠糖尿病模型,但四氧嘧啶50mg/kg剂量组大鼠死亡率较大,只有40mg/kg组糖尿病大鼠模型稳定.结论:造成小鼠和大鼠糖尿病模型最佳剂量分别为60mg/kg和40mg/kg.     

大鼠肝癌发生过程中血清白细胞介素-2的检测及意义

目的:研究白细胞介素-2(IL-2)在肝癌发生过程中的表达及意义。方法:采用二乙基亚硝胺建立大鼠肝癌模型。应用酶联免疫吸附法(ELISA)检测诱癌过程中血清IL-2的表达变化。结果:大鼠血清IL-2水平随病变进展而逐渐降低,癌变组血清IL-2浓度低于正常对照组、肝细胞损伤组及增生-硬化组。结论:检测血清IL-2水平有助于了解病情发展和机体免疫状态,是早期发现癌变的敏感指标。     

早期卵裂环境与小鼠植入前胚胎GCN5和HDAC1表达的研究

应用免疫细胞化学技术对体内、外组小鼠植入前胚胎组蛋白乙酰基转移酶GCN5(generalcontrolofnucleotidesynthesis,GCN5)和去乙酰化酶HDAC1(histonedeacetylase1)的表达情况进行测定研究。结果显示(1)体内组:GCN5在2细胞、4细胞、8细胞卵裂胚胎和桑椹胚的胞浆内为强荧光信号;而囊胚细胞的胞浆无明显荧光信号。HDAC1在2细胞的胞浆胞核内均有荧光信号,但以胞浆内为著;4细胞、8细胞、桑椹胚和囊胚的胞核内可见HDAC1强荧光信号。(2)体外组:2细胞、4细胞、8细胞、桑椹胚和囊胚的胞浆胞核均无明显的GCN5荧光信号。HDAC1在各细胞期胚胎的染色情况与体内组基本相似,只是荧光强度有所下降,尤其是2细胞胚胎。结果表明:早期卵裂环境影响小鼠植入前胚胎GCN5和HDAC1表达。     

SXP–RAL Family Filarial Protein,rWbL2, Prevents Development of DSS-Induced Acute Ulcerative Colitis

Helminthic infections lead to the release of various molecules which play an important role in modulation of the host immune system. Such filarial proteins with immunomodulatory potential can be used for therapeutic purpose in inflammatory and immune mediated diseases. In the present study, we have explored the prophylactic effect of filarial SXP–RAL family protein of Wuchereria bancrofti i.e. rWbL2 protein in DSS induced inflammatory ulcerative colitis in a mouse model. Prior treatment of rWbL2, followed by induction of colitis, showed significantly reduced disease severity as indicated by the decreased disease manifestations and improved macroscopic and microscopic inflammation. This preventive effect was found to be associated with increased release of anti-inflammatory cytokine IL-10 and decreased release of proinflammatory cytokines IFN-γ, TNF-α, IL-6 and IL-17 by the splenocytes of treated mice. From this study, it can be envisaged that pretreatment with filarial protein, rWbL2, can prevent the establishment of ulcerative colitis in BALB/c mice. The underlying immunological mechanism may involve the up-regulation of Th2 immune response with down-regulation of Th1 response.     

Immunomodulation of ovalbumin-specific IgG and other classes of antibody response by honey in mice

It was reported earlier that intraperitoneal administration of honey had immunosuppressive activity on elicitation of allergen-specific murine antibody response as evaluated by passive cutaneous anaphylaxis and double immunodiffusion methods. In this study, the immunomudulatory effect of honey is evaluated by enzyme linked immunosorbent assay (ELISA) using ovalbumin as model allergen. It was found that ovalbumin (OVA)-specific IgG antibody responses elicited with various doses of OVA were significantly suppressed by rock bee honey (p<0.01). Honey was also found to have inhibited the production of OVA-specific IgM, IgA, IgG₁, and IgG_2b whereas that of IgG_2a and IgG₃ were not affected. Furthermore, honey also suppressed the OVA-specific total IgG antibody response in various inbred mice with different genetic background. In addition, the suppressive activity of honey was examined in different groups of mice by injecting honey at different time intervals, before and after immunization with OVA. The anti-OVA IgG antibody response was suppressed significantly when honey was injected 12 hours prior/latter to OVA injection. These results confirm the suppressive activity of honey on antibody response and suggest possible clinical application.     

Induction of Multiple Sclerosis and Response to Tyrosine Kinase Inhibitors

The goal of this work is to determine the role of the autoimmune cells in multiple sclerosis (MS) induction and the immunomodulatory mechanism of therapy with tyrosine kinase inhibitors (TKIs) in MS attenuation. Samples (5 × 10⁵ cells per well) of C6 and primary rat astrocytes were stimulated with 10 ng/mL of platelet-derived growth factor (PDGFbb) as a positive control forming a mouse model of MS. PDGFbb was added to the astrocytes in the absence or presence of 0.1 and 1 μM of imatinib. Proliferation of C6 and primary rat astrocytes samples were assessed for samples staging by the addition of 1 μCi of ³H-thymidine per well. Samples of RAW 264.7 cells were stimulated for 48 h with 10 ng/mL of PDGFbb in the absence or presence of 0.1 and 1 μM of sorafenib. Tumour necrotic factor (TNF) levels in culture supernatants from RAW 264.7 cells were measured by ELISA. The histologic grade (H_G) and the level of TNF of the mouse model of MS was 1/5 and 5 times respectively of those in the control one to clarify that MS induction is due to a major decrease in H_G inversely proportional to the accompanied increase in TNF level perpetuating local inflammation and demyelination in MS lesion. The addition of 0.1 and 1 μM doses of imatinib increased H_G of the mouse model of MS by 6 and 11 times respectively while 0.1 and 1 μM doses of sorafenib decreased TNF level to be 1/2 and 1/5 of that in the mouse model of MS respectively restoring normal rate of TNF level of normal lesion to show that H_Gand TNF level would be strongly inversely correlated (r = −0.99) in attenuating MS effectively by TKIs therapy but not in an inverse proportion as in MS induction.     

Antioxidant effect of carnosine pretreatment on cisplatin-induced renal oxidative stress in rats

Cisplatin mediated nephrotoxicity is remarkably documented by reactive oxygen species. Carnosine is a naturally occurring dipeptide and has a scavenging property. The aim of present study was to assess the lipid peroxidation and antioxidant enzymes in association with oxidative stress in cisplatin -treated and 10 subsequent doses of carnosine-pretreated rats. 24 male Albino Wistar rats, were randomly divided into four groups (n=6). Group I remains untreated; Group II received Cisplatin (3 mg / kg) for 5 alternate days; Group III received Carnosine (10 mg / kg) for consecutive 10 days; Group IV received Carnosine (10 mg / kg) before administration of Cisplatin (3 mg / kg). The effects of carnosine on cisplatin-induced nephrotoxicity were evaluated by plasma creatinine, urea, malondialdehyde, nitrate; kidney tissue malondialdehyde, 4-HNE, superoxide dismutase and catalase activities. Cisplatin-induced oxidative stress was indicated by increased level of tissue MDA, 4-HNE and decreased level of tissue GSH, SOD and Catalase. Marked elevation of kidney weight and reduced body weight and pathological changes in kidney tissues were also observed in Cisplatin-treated rats. Carnosine reduced these pathological changes and counteracted the deleterious effects of cisplatin. The results divulge the beneficial effect of Carnosine pretreatment with cisplatin in experimental rat model.     

TCTE3mRNA在人肝癌细胞株中的表达特征

探讨TCTE3 mRNA在人肝癌细胞株中的表达水平及意义。采用实时荧光定量PCR技术分别检测TCTE3基因在常规培养或缺氧诱导（CoCl2为诱导剂）的人肝癌细胞株中的表达情况。TCTE3 mRNA在常规培养的人正常肝细胞株L02,肝癌细胞株Bel-7402、SMMC-7721、HepG2和QGY-7701中不表达或极低表达;但经缺氧诱导后,SMMC-7721细胞中的TCTE3 mRNA表达量逐渐升高,4h达到最大,随后逐渐降低,与HIF1a mRNA表达的曲线变化有一定相似之处,只是这种变化的时间要早于HIF1a基因。在缺氧状态下肝癌细胞TCTE3 mRNA表达增加,且这种上调表达可能对HIF1a mRNA的表达有一定的促进作用。     

乳腺癌耐受蛋白介导5-氟脲嘧啶的耐受及机制探讨

AIM To filtrate breast cancer resistance protein(BCRP)-mediated resistance agents and investigate the mechanism,so as to provide valuable datum for optimization clinical chemotherapy scheme to tumor with evaluation marker of BCRP expression. METHODS MTT assay was used to filtrate BCRP-mediated resistance agents with PA317/Tet-on/TRE-BCRP cell of different expression levels of BCRP after treated with different concentration anticancer agents. High performance liquid chromatography(HPLC) was applied to measure relative dose of intracellular retention resistance agents. Nuclear DNA fluorescence dye,Hochest 33258, staining and flow cytometry were adopted to detect apoptotic cells after treated with drugs. RESULTS There were shown increasing durg-resistance to 5-fluorouracil,methotrexate, doxirubicin, pirarubicin,etoposide and mitoxantrone followed with increasing expression of BCRP on PA317/Tet-on/TRE-BCRP cells(P＜0.05, n=3),but shown sensitive to paclitaxel, cisplatin, vincristine, mitomycin and vindesine. There also was shown significant negative correlation between the intracellular retention dose of 5-fluorouracil with different expression of BCRP(r=-0.885, P＜0.05, n=3).There were shown parallel results of that decreasing cellular apoptotic rate with increasing cellular expression of BCRP after treated with 5-fluorouracil by fluorescence dye staining and flow cytometry(P＜0.05, n=3),and also shown significate rise of the apoptotic rate of BCRP expression cells after treated with Ko143 (P＜0.05, n=3). Every group of cells could be different extently blocked in phase of G0/G1 treated with 5-fluorouracil. CONCLUSION Resistance of 5-fluorouracil could be especially mediated by conjugated with BCRP and acted as drug exclude-pump substrate. Cellular ability resistant to 5-fluorouracil-induced apoptosis could be reinforced by BCRP expression.     

钒对遗传性Ⅱ型糖尿病ＫＫ小鼠降糖作用的实验研究

以遗传性非胰岛素依赖型糖尿病ＫＫ小鼠为动物模型,研究钒对雌雄性糖尿病小鼠的降糖作用．实验选择３周龄的ＫＫ小鼠,雌雄各半,通过自由饮水方式给予雌雄性小鼠０ｍｇ/Ｌ、０.１ｍｇ/Ｌ和１００ｍｇ/Ｌ的钒酸铵,实验周期为１７周,观察不同剂量钒酸铵对血糖、甘油三酯和总胆固醇代谢的影响．研究结果表明,０１ｍｇ?Ｌ钒酸铵对雌雄性小鼠的血糖水平和血液生化指标没有明显的影响,高剂量钒酸铵（１００ｍｇ?Ｌ）明显降低雄性糖尿病小鼠的饮水量、血糖水平、糖基化血红蛋白、甘油三酯和总胆固醇等,葡萄糖耐量水平得到显著改善,对糖尿病小鼠的肝肾功能没有影响．结果提示钒酸铵对雌性小鼠和雄性小鼠具有降血糖作用,其作用效果有明显的性别差异．     

Arabidopsis, the botanical Drosophila: from mouse cress to model organism

The small flowering plant Arabidopsis thaliana is the best-studied model organism in plant biology. More resources are allocated to research on this little weed than to the study of well-known favourites such as worms, fruit flies and mice. Yet, up to the early 1980s plant biologists had every good reason to ignore Arabidopsis: neither did it seem to possess the characteristics of a good model organism, nor did it have any agricultural promise. The sudden prestige acquired by Arabidopsis research thus constitutes a remarkable historical puzzle. What made the mouse cress into the most successful model organism to date?