动力相关蛋白Drp1在羊瘙痒因子139A感染小鼠脑组织中变化的研究

目的 研究动力相关蛋白1(Drp1)在羊瘙痒因子139A感染的小鼠脑组织中的变化。方法 采用Western Blot方法检测Drp1在羊瘙痒因子139A感染的脑组织匀浆中的含量变化及其亚硝基化水平。采用组织免疫荧光方法检测Drp1在脑组织中的分布。结果 在羊瘙痒因子139A感染终末期小鼠脑组织匀浆中,Drp1总量略有降低。对感染不同时间点的动态分析结果显示Drp1含量呈逐渐降低趋势,终末期稍有回升。感染终末期脑组织中亚硝基化水平明显增高。组织免疫荧光显示正常和羊瘙痒因子139A感染终末期小鼠脑组织中,Drp1与神经元细胞存在共定位现象。结论 Drp1在小鼠中枢神经系统中主要分布于神经元细胞,在羊瘙痒因子139A感染的小鼠脑组织中,Drp1总量略有降低,另外亚硝基化水平明显增高,提示在羊瘙痒病感染的小鼠脑组织中,线粒体动力相关蛋白的表达量及翻译后修饰水平出现了变化,在感染过程中起着重要作用。     

CXCL1/CXCR2在羊瘙痒因子感染小鼠脑组织中的分布特征研究

目的 探究朊病毒感染小鼠脑组织CXC趋化因子配体1 (CXCL1)与CXC趋化因子受体2 (CXCR2)的分布特征。方法 通过免疫组织化学、免疫组织荧光双染实验明确羊瘙痒因子139A及ME7感染终末期小鼠脑组织中CXCL1/CXCR2的分布特征,确定CXCL1/CXCR2的靶细胞及与羊瘙痒因子样朊蛋白(PrPSc)沉积的关系。结果 通过全脑区免疫组化染色发现,CXCL1/CXCR2在羊瘙痒因子139A及ME7感染终末期小鼠脑组织中的含量明显升高,主要分布在海马、皮层、丘脑、小脑及延髓5个脑区。CXCL1与小胶质细胞和神经元细胞存在共定位,而CXCR2与神经元细胞存在共定位。在羊瘙痒因子139A及ME7感染终末期小鼠脑组织中CXCL1、CXCR2和PrP^Sc三者存在明显共定位。结论 CXCL1/CXCR2分布于朊病毒感染小鼠脑组织中朊病毒病理特征集中的脑区。     

羊瘙痒因子139A感染引起小鼠脑组织中的1-ACT表达增加

目的 探究1-ACT在羊瘙痒因子139A感染小鼠脑组织中的变化情况。方法 利用蛋白免疫印迹、免疫组织化学、间接免疫荧光及荧光共聚焦方法分析羊瘙痒因子139A感染小鼠脑组织中1-ACT表达的变化和分布特点。结果 蛋白免疫印迹方法显示在羊瘙痒因子139A感染小鼠终末期脑组织中1-ACT的含量较正常对照小鼠明显上调且随着潜伏期的延长而逐渐增加;免疫组织化学方法发现1-ACT主要分布于羊瘙痒因子139A感染小鼠的皮层、丘脑和小脑区域;间接免疫荧光实验显示羊瘙痒因子139A感染终末期小鼠脑组织中补体成分C3含量明显增加,同时荧光共聚焦实验表明1-ACT与补体成分C3存在明显的共定位现象。结论 羊瘙痒因子139A感染终末期小鼠脑组织中1-ACT含量明显增加。     

儿童急性淋巴细胞白血病核转录因子κB的表达及其意义

为了探讨儿童急性淋巴细胞白血病（ALL）NF-κB P65蛋白的表达及意义,应用SP免疫组织化学法检测32例ALL患儿和40例非血液病的对照儿童NF-κBP65蛋白的表达。结果表明：32例ALL患儿的NF-κB P65蛋白的阳性表达率为87.50%（28/32）,表达定位于ALL细胞的胞核及胞浆中,阳性表达率明显高于对照组12.50%（5/40）,两者比较有显著性差异（χ2=40.28,p〈0.01）。在28例ALL患儿组阳性表达者中,弱阳性表达（＋）占10.71%（3/28）,阳性表达（＋＋）占42.86%（12/28）,强阳性表达（＋＋＋）占46.43%（13/28）。正常对照组均为弱阳性表达（5/5）,两者表达程度经Ridit分析差异有显著意义（p〈0.01）。ALL病程间（初发或复发）、免疫表型间（T系ALL与B系ALL）、各细胞形态学间的表达程度差异均无显著意义（p〉0.05,四格表精确概率法）。结论：NF-κB P65蛋白表达于儿童ALL细胞中,抑制NF-κB信号传导途径可能在儿童ALL治疗中有重大价值,这为临床寻求以NF-κB为靶点的治疗手段提供了科学依据。     

细菌脂蛋白耐受中核转录因子核转位机制研究

目的 探讨细菌脂蛋白(BLP)耐受所致核转录因子-κB(NF-κB)活化受抑制的分子机制.方法 以不同浓度BLP(10、100、1 000 ng/ml)预处理人急性单核细胞白血病细胞(THP-1)诱导BLP耐受,再以不同浓度BLP(0、10、100、1 000 ng/m1)刺激经BLP预处理(耐受组)或未经BLP预处理(对照组)的THP-1细胞,采用酶联免疫吸附法(ELISA)检测培养上清中肿瘤坏死因子-α(TNF-α)的释放,确定最适的BLP预处理和刺激浓度.然后按此条件处理细胞不同时间(0、0.5、1、2、6 h)并提取蛋白,用蛋白质免疫印迹法(Western blotting)检测NF-κB亚单位p50和p65的表达、核转位及磷酸化情况.结果 对照组中10、100、1 000 ng/mlBLP可剂量依赖性刺激THP-1活化并产生TNF-α(pg/ml:184.86±32.51、3 215.88±167.09、6 042.96±245.37),耐受组中100 ng/ml BLP预处理几乎完全抑制不同剂量BLP诱导的TNF-α释放.故最适BLP预处理浓度为100 ng/ml,刺激浓度为1 000 ng/ml.Western blotting检测表明,在BLP耐受的细胞质中p50蛋白表达明显高于对照组(0 h:542.9±15.6比272.8±13.2,0.5 h:558.0±16.9比236.4±11.8,1 h:524.7±17.5比211.6±9.8,2 h:584.9±15.6比222.4±12.3,均P＜0.01),而两组间p65蛋白无明显差异.BLP刺激还可诱导对照组细胞中p50和p65发生核转位,即细胞核中p50和p65蛋白增加(1 h p50:344.2±13.6比79.0±5.2,p65:78.4±4.5比0,均P＜0.05),而耐受组细胞核中p50和p65均无明显变化.另外,BLP刺激还可诱导对照组细胞中p65的536位丝氨酸发生快速磷酸化(0.5 h:0.67±0.08比0.04±0.01,1 h:0.71±0.11比0.04±0.01,均P＜0.05).但是在BLP刺激的耐受组细胞中磷酸化p65蛋白水平无明显变化.结论 BLP耐受的THP-1细胞中抑制性NF-κB亚单位p50表达上调,而具有转活化能力的亚单位p65的核转位及磷酸化均受到抑制,可能是BLP耐受中TNF-α等NF-κB依赖的基因表达减少的分子机制之一.

Abstract：

Objective To approach the nuclear factor-κB (NF-κB) nuclear translocation mechanism in bacterial lipoprotein (BLP) tolerance. Methods Human monocytic THP-1 cells were first pretreated with 10, 100, 1 000 ng/ml BLP for 20 hours to induce BLP tolerance. Then THP-1 cells without BLP pretreatment (control group) or with BLP pretreatment (tolerance group) were stimulated with 0, 10, 100,1 000 ng/ml BLP again for 6 hours. The tumor necrosis factor-α (TNF-α) content in culture medium was measured by enzyme linked immunosorbent assay (ELISA) in order to determine the most suitable BLP pretreatment and stimulation concentration. Western blotting was used to detect the protein level, nuclear translocation and phosphorylation of NF-ΚB p50 and p65 in the cells of control and tolerance groups treated with respective conditions for 0, 0.5, 1, 2 and 6 hours. Results In control group BLP stimulation (10,100, 1 000 ng/ml) could induce THP-1 activation and TNF-α production (pg/ml: 184.86 ± 32. 51,3 215. 88±167. 09, 6 042. 96±245. 37) in a dose-dependent manner. In tolerance group, 100 ng/ml BLP pretreatment resulted in almost complete inhibition of TNF-α production as induced by 10-1 000 ng/ml BLP stimulation. Therefore, 100 ng/ml BLP pretreatment and 1 000 ng/ml stimulation were selected for following cell treatment. Western blotting analysts showed that there was an increase of p50 protein level in BLP-tolerant cells comparing with control group (0 hour: 542. 9±15. 6 vs. 272. 8±13. 2, 0. 5 hour: 558. 0±16. 9 vs. 236. 4±11.8, 1 hour: 524. 7±17. 5 vs. 211. 6±9. 8, 2 hours: 584. 9±15. 6 vs. 222. 4±12. 3, all P＜0. 01), whereas the p65 protein level was similar between the two groups. BLP stimulation also induced the nuclear translocation of p50 and p65 in control group (1-hour p50: 344. 2±13. 6 vs. 79. 0±5. 2, p65:78. 4 ±4.5 vs. 0, both P＜0. 05), but not in tolerance group. In addition, the phosphorylation of p65 at serine 536 was induced after BLP stimulation in control THP-1 cells (0. 5 hour: 0. 67±0. 08 vs. 0. 04±0. 01,1 hour: 0.71±0.11 vs. 0.04±0.01, both P＜0.05), but this change was not detected in BLP-tolerant cells. Conclusion It was found that in BLP-tolerant cells, the expression of inhibitory subunit p50 was increased and the nuclear translocation and phosphorylation of p65 with trans-activation ability was inhibited.These changes are likely responsible for the reduced gene expression of NF-ΚB dependent genes in BLP-tolerant cells.     

血管内皮生长因子和核转录因子p65在多形性腺瘤中的表达及其意义

目的 探讨血管内皮生长因子(VEGF)和核转录因子(NF-κB)p65在不同分型的多形性腺瘤中的表达及意义.方法 涎腺多形性腺瘤患者60例,其中细胞丰富型31例,基质丰富型29例,取瘤旁正常涎腺组织30份,应用免疫组织化学技术检测组织中VEGF、NF-κBp65的表达.结果 (1)VEGF表达主要以肿瘤性上皮组织较多,多为实性上皮条索、腺管样结构区域,染色强度不尽相同.(2)多形性腺瘤组织中NF-κB p65阳性表达主要见于腺泡上皮和导管上皮,呈强阳性染色;间质成分中血管上皮呈弱阳性表达、纤维结缔组织呈弱阳性表达;黏液样组织和软骨样组织未见明显阳性表达.(3)VEGF在细胞丰富型腺瘤中平均吸光度(MA)值为955.67±305.79,基质丰富型MA值为149.13±60.85,正常对照组MA值为53.46±9.66,两两比较差异均有统计学意义(P均＜0.05).(4)NF-κB p65在细胞丰富型腺瘤MA值为529.80±164.81,基质丰富型为43.40±5.46,正常对照组为6.84±1.91,两两比较差异均有统计学意义(P均＜0.05).<5)涎腺多形性腺瘤中NF-κB p65与VEGF表达呈正相关(r=0.854,P＜0.05).结论 (1)涎腺多形性腺瘤新生血管形成能力及细胞增殖活性随着瘤体中细胞成分的增多而逐渐升高,细胞丰富型多形性腺瘤较基质丰富型多形性腺瘤具有更易恶变的倾向.(2)NF-κB p65可能是通过作用于VEGF来实现对新生血管的调控作用.

Abstract：

Objective To investigate the expression and significance of VEGF and NF-κB/p65 in the two subtypes of pleomorphic adenoma. Methods Immunohistochemistry was applied to detect the expression of VEGF and NF-κB/p65 in pleomorphic adenoma of 60 patients including 31 cases of cell-rich and 29 cases of stroma-rich as well as normal salivary gland tissues of 30 cases from adjacent tumor. Results VEGF positive staining was mainly found in tumor epithelia,while NF-κB/p65 positive was detected in gland alveolus cell and ductal epithelia. The Mean optical density( MA ) values of VEGF were 955.67 ± 305.79,149. 13 ± 60. 85 and 53.46 ± 9. 66, respectively, in cell-rich adenoma, stroma-rich adenoma and normal control. The difference in VEGF expression between the groups was significant (Ps ＜ 0. 05 ) . The MA values of NF-κB/p65 were 529. 80 ± 164. 81,43.40 ±5.46 and 6. 84 ± 1.91 ,respectively,in three groups mentioned above. The difference in NF-κB/p65 expression between the groups was significant ( Ps ＜ 0. 05 ). In pleomorphic adenoma, the expression level of NF-κB/p65 was positively correlated with VEGF. Conclusion ( 1 ) The angiogenesis and proliferation potential of carcinomas increased with the cell component in pleomorphic adenoma. Stroma-poor adenoma is more frequently subjected to malignant transformation than stroma-rich adenoma. (2) NF-κB/p65 may have effects on angiogenesis by activating VEGF. Detecting the expression of VEGF and NF-κB/p65 may be helpful to predict the biological behavior of pleomorphic adenoma and prognosis of the patients, which couldprovide useful information for future targeted therapy of pleomorphic adenoma.     

P38丝裂原活化蛋白激酶和核转录因子κBP65在胸部爆炸伤致急性肺损伤中的作用

目的探讨P38丝裂原活化蛋白激酶(P38MAPK)和核转录因子κBP65(NFκBP65)活化在胸部爆炸伤致急性肺损伤(ALI)中的作用。方法应用胸部爆炸伤致ALI动物实验模型,原位分子杂交技术检测P38MAPK和NFκB P65mRNA表达情况,并与致伤后ALI发病程度进行相关性统计分析。结果肺组织中P38MAPK和NFκB P65mRNA表达情况与PaO2,P(A-a)O2、TNF-α及IL-6水平呈正相关,与急性肺损伤肺炎症反应的严重程度存在一致性。结论P38MAPK和NFκB P65活化在胸部爆炸伤致急性肺损伤(ALI)中起着重要作用,设法减弱其活化程度可能是防治ALI的有效途径。     

糖尿病大鼠肺组织中核转录因子-κB及其抑制因子信号通路的表达变化

目的 探讨核转录因子-κB(NF-κB)信号通路激活对糖尿病肺损伤的影响.方法 通过高糖、高脂饮食加腹腔注射小剂量链尿佐菌素(STZ)的方法,建立2型糖尿病大鼠模型,采用光镜动态观察12、24周时,对照组(20只)、糖尿病组(30只)大鼠肺组织的形态学改变情况,用Masson三色染色观察肺组织胶原沉积情况,应用免疫组织化学方法检测2组肺组织NF-κB p65、IκBα、蛋白激酶C的变化情况.结果 光镜下糖尿病大鼠肺组织结构紊乱,肺泡间隔增厚,周围细胞外基质增多,局部纤维化,随病情进展,表达愈加明显.12、24周糖尿病大鼠肺组织NF-κB p65的吸光度值为0.20±0.0l、0.35±0.06,高于同期对照组的0.12±0.02、0.17±0.03,差异有统计学意义(P均＜0.01),12、24周糖尿病肺组织IκB的吸光度为0.29±0.02、0.36±0.03,分别高于同期对照组的0.08±0.02、0.22±0.08,差异有统计学意义(P均＜0.01).结论 NF-κB及其IκB信号通路的激活参与糖尿病肺组织病变的发生发展,可能是肺损伤的机制之一.

Abstract：

Objective To investigate the effect of activation of NF-κB signaling pathway on pathogenesis of lung in diabetes mellitus(DM) rat. Methods The experimental type 2 diabetic rats were built by injecting streptozotocin (STZ) and feeding with high fat and glucose food. At the 12nd and 24th week, we observed the alteration of morphology in the lung of rats in the control group(20 rats) ,the DM group(30 rats)using spectroscopic analysis. The collagen accumulation of lung was observed by masson trihrome staining, and alteration of NF-κB P65, IκBα, and PKC in lung was observed by immunohistochemistry. Results The tissue structure of lung in the DM rats distributed deranged in the light microscope, alveolar wall were thicken, extracellular matrixes increased and pulmonary fibrosis appeared. With the development of pathogenic condition, the expression increased obviously. The staining optical density value of NF-κB P65 in tissue of lung in the 12 w and 24 w DM group were 0. 20 ± 0. 01 and 0. 35 ± 0. 06 respectively, which was significantly higher than those of the control group at the corresponding time point ( 0. 12 ± 0. 02 and 0. 17 ± 0. 03, respectively, Ps ＜ 0. 0l ). The staining optical density value of IκB in tissue of lung in the 12 w and 24 w DM group were 0. 29 ±0. 02 and 0. 36 ± 0. 03, respectively, which were significantly higher than those of the control at the corresponding time point (0. 08 ± 0. 02 and 0. 22 ± 0. 08, respectively, Ps ＜ 0. 01 ). Conclusion The signaling pathway of NF-κB/IκB participate in the occurrence and development in the pathogenesis of lung in DM, and may be one of the mechanisms of lung injury.     

血必净对创伤弧菌脓毒症大鼠肺组织核因子-κB p65表达作用的研究

目的 观察创伤弧菌脓毒症大鼠肺组织核因子-κB(NF-κB)p65基因及蛋白表达,并探讨血必净对其的干预作用.方法 SD大鼠110只,随机分为正常组(A组,n＝10)、创伤弧菌脓毒症组(B组,n＝50,采用大鼠左下肢皮下注射创伤弧菌悬液制作大鼠创伤弧菌脓毒症模型)和血必净治疗干预组(C组,n＝50,感染后半小时腹腔注射血必净4 mL/kg).B、C组于染菌后1、6、12、24、48 h活杀(各时间点n=10),采用逆转录-聚合酶链式反应(RT-PCR) 法、Western blot法和双抗体夹心酶联免疫吸附法(ELISA)分别检测大鼠肺组织NF-κB p65的基因与蛋白表达及IL-10的含量,数据采用单因素方差分析.结果 与A组比较,B组大鼠肺组织创伤弧菌感染后6、12 h NF-κB p65 mRNA表达量与6、12、24和48 h肺组织NF-κB p65蛋白表达量均明显增高 (P<0.05);与B组相同时间点比较,C组6 h肺组织NF-κB p65 mRNA表达量与12、24及48 h肺组织NF-κB p65 蛋白表达量明显减少(P<0.05); 与A组比较,B组创伤弧菌菌感染12、24和48 h IL-10的含量明显增加(P<0.05),与B组相同时间点比较,C组24 h(52.444±9.605)肺组织IL-10的含量明显增高(P<0.05);感染后48 h,大鼠肺内血管明显充血,间质水肿并伴炎性浸润,肺泡腔塌陷,血必净干预后,肺组织损伤有所减轻.结论 NF-κB参与了创伤弧菌脓毒症肺损伤过程;血必净能抑制NF-κB p65的表达,从而起到保护创伤弧菌脓毒症大鼠肺组织的作用.     

卵巢上皮性肿瘤组织中黏蛋白抗原4和核因子-κB/p65蛋白表达及临床意义

目的探讨黏蛋白抗原4(MUC4)及核因子(NF-κB/p65)在卵巢癌组织中的表达及临床意义。方法通过免疫组化方法,用MUC4及NF-κB/p65抗原检测正常卵巢组织和卵巢上皮性肿瘤组织中MUC4、NF-Kb/p65的表达,分析其临床意义。结果在卵巢癌中MUC4、NF-Kb/p65蛋白的阳性表达率分别为80%、92.30%,与卵巢交界性、良性及正常卵巢组织两两相比,差异均有统计学意义,且MUC4和NF-Kb/p65阳性表达与肿瘤分化程度、淋巴结转移明显相关(P<0.05)。结论 MUC4和NF-κB/p65蛋白表达与卵巢癌分化程度、淋巴结转移关系密切,MUC4可望作为卵巢癌早期诊断的标志物,黏附分子的表达可能受核转录因子的调控。     

脑病损后构音障碍的诊评：附65例临床报告

应用弗朗蔡构音障碍评法对６５例构音障碍患者进行诊评，发现脑血管病后构音障碍以痉挛型多见，共５７例占８７．８％，依次是弛缓型、运动失调型、运动过弱型。该评价法能比较全面系统地对脑病损后构音障碍进行诊断分型与鉴别诊断，为临动态的观察病情变化及疗效判定，提供可靠的客观依据，同时能对判断预后有一定指导作用。     

EV71感染对小鼠脑组织p38MAPK信号通路影响的研究

目的研究肠道病毒71(EV71)感染对小鼠脑组织p38MAPK信号通路的影响。方法利用实验室筛选出的具有较强致病能力的EV71-GZCH43-3株,采用不同的病毒滴度(103PFU/ml,105PFU/ml,107PFU/ml)感染2周龄的ICR幼鼠,建立轻、中、重三种不同程度的幼鼠感染模型,病理切片观察其肺组织病理变化;利用流式细胞术检测感染模型幼鼠中CD4+CD25+Foxp3+Treg细胞的变化情况;反转录酶-聚合酶链式扩增反应(RT-PCR)方法检测p38MAPK信号途径基因的表达变化;酶联免疫分析法(ELISA)检测小鼠血清中肿瘤坏死因子α(TNF-α)、干扰素(IFN-γ)水平的变化情况。结果成功建立轻、中、重三种不同感染滴度的EV71感染幼鼠模型,其肺组织明显充血;流式细胞术结果显示随着病毒感染滴度的增加,Treg细胞的数目明显增加;ELISA结果表明随病毒滴度增加IFN-γ表达量增加,高滴度组大约是对照组的30倍;TNF-α先随病毒滴度增加而略有降低,随后在高滴度组又明显升高。结论表明EV71感染可能通过影响p38MAPK信号途径基因的表达而间接调节TNF-α和IFN-γ体内表达,诱导宿主病理性免疫反应,引起宿主免疫功能的紊乱。     

结直肠癌组织中锌指蛋白139(ZNF139)的表达及临床意义研究

目的 探究锌指蛋白139(zinc finger protein 139,ZNF139)在结直肠癌(colorectal cancer)组织中的表达及与临床病理参数及预后的关系。方法 选取2012年5月～2014年6月就诊于恩施土家族苗族自治州中心医院行手术治疗的67例结直肠癌患者的临床病理资料及癌组织、癌旁组织和正常黏膜组织进行研究。采用实时荧光定量逆转录聚合酶链反应(RT-PCR)和免疫组织化学法染色检测ZNF139 mRNA及蛋白在结直肠癌组织中的表达情况,分析其与结直肠癌患者临床病理因素的关系;采用K-M生存曲线分析ZNF139表达对预后的影响;采用COX回归模型分析影响结直肠癌患者预后的风险因素。结果 结直肠癌病灶组织中ZNF139 mRNA(0.651±0.130)表达水平明显高于癌旁组织(0.217±0.070)和正常组织(0.201±0.052),差异有统计学意义(t=24.060, 24.947,均P=0.001)。结直肠癌组织中ZNF139蛋白阳性率(52.24%)明显高于癌旁组织(28.36%)和正常黏膜组织(19.40%),差异均有统计学意义(χ²     

刺五加干预后新生大鼠缺血缺氧脑组织前列腺素的代谢改变

目的:探讨益气活血中药刺五加对新生大鼠缺血缺氧脑组织前列腺素代谢改变的影响。方法:实验于2003-04/08在延边大学医院儿科疾病研究室进行。取新生7d的Wistar大鼠36只,随机分成3组:①正常组(n=10):不干预。②缺氧缺血脑病组(n=13):麻醉后结扎左侧颈总动脉,1h后置于37℃密封缺氧箱内,以2.0～3.0L/min速度吸入含体积分数为0.08的氧气的气体,持续2h,制备脑组织缺血缺氧动物模型。③刺五加组(n=13):制备模型同前,模型成功后即刻腹腔注射刺五加(10mL/kg,5g/L)。3组动物在48h后取材,用放射免疫分析法测量新生大鼠脑组织中前列腺素血栓素B2,6-酮-前列腺素F1含量变化。结果:实验中6只动物死亡,30只进入结果分析。①脑组织6-酮-前列腺素F1含量:缺氧缺血脑病组显著高于正常组和刺五加组犤(22.23±5.95),(13.63±2.50),(10.62±1.40)ng/g,F=11.618,P<0.01犦,正常组和刺五加组无差异(P>0.05)。②脑组织血栓素B2含量:缺氧缺血脑病组显著高于正常组和刺五加组犤(13.67±2.35),(9.11±0.96),(10.58±1.80)ng/g,F=13.248,P<0.01犦,正常组和刺五加组无差异(P>0.05)。结论:缺血缺氧模型脑组织中血栓素B2和6-酮-前列腺素F1含量明显增高,说明存在血栓素及前列腺素代谢紊乱,易形成血栓。刺五加能显著降低脑组织中此两种因子的含量,对缺血缺氧脑组织前列腺素代谢方面有保护作用。     

刺五加干预后新生大鼠缺血缺氧脑组织前列腺素的代谢改变

目的：探讨益气活血中药刺五加对新生大鼠缺血缺氧脑组织前列腺素代谢改变的影响、方法：实验于2003—04／08在延边大学医院儿科疾病研究室进行。取新生7d的Wistar大鼠36只．随机分成3组：①正常组（n=10）：不干预。②缺氧缺血脑病组（n=13）：麻醉后结扎左侧颈总动脉，1h后置于37℃密封缺氧箱内，以2．0～3．0L／min速度吸入含体积分数为0．08的氧气的气体，持续2h，制备脑组织缺血缺氧动物模型。③刺五加组（n=13）：制备模型同前．模型成功后即刻腹腔注射刺五加（10mL/kg，5g／L）。3组动物在48h后取材，用放射免疫分析法测量新生大鼠脑组织中前列腺素血栓素B2，6-酮-前列腺素F1含量变化。结果：实验中6只动物死亡，30只进入结果分析。①脑组织6-酮-前列腺素F1含量：缺氧缺血脑病组显著高于正常组和刺五加组[（22．23&;#177;5．95），（13．63&;#177;2．50），（10．62&;#177;1．40）ng／g，F=11．618，P〈0．01]，正常组和刺五加组无差异（P〉0．05）。②脑组织血栓素B2含量：缺氧缺血脑病组显著高于正常组和刺五加组[（13．67&;#177;2.35），（9．11&;#177;0．96），（10．58&;#177;1．80）ng／g，F=13．248，P〈0．01]，正常组和刺五加组无差异（P〉0．05）。结论：缺血缺氧模型脑组织中血栓素B2和6-酮-前列腺素F1含量明显增高，说明存在血栓素及前列腺素代谢紊乱，易形成血栓。刺五加能显著降低脑组织中此两种因子的含量，对缺血缺氧脑组织前列腺素代谢方面有保护作用。     

RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice

Osteoclasts (OCs) function to reabsorb bone and are responsible for the bone loss associated with inflammatory arthritis and osteoporosis. OC numbers are elevated in most disorders of accelerated bone destruction, reflecting altered rates of precursor differentiation and apoptosis. Both of these processes are regulated by the JNK family of MAP kinases. In this study, we have demonstrated that the NF-kappaB subunit RelA/p65 inhibits JNK-mediated apoptosis during a critical period of commitment to the OC phenotype in response to the cytokine RANKL. This RelA/p65-mediated arrest of cell death led to enhanced OC differentiation. Hence, Rela-/- OC precursors displayed prolonged JNK activation in response to RANKL, and this was accompanied by an increase in cell death that prevented efficient differentiation. Although complete blockade of JNK activity inhibits osteoclastogenesis, both short-term blockade in RelA-deficient cultures and suppression of the downstream mediator, Bid rescued apoptosis and differentiation. These antiapoptotic effects were RelA specific, as overexpression of RelA, but not RelB, blocked apoptosis and rescued differentiation in Rela-/- precursors. Thus, RelA blocks a RANKL-induced, apoptotic JNK-Bid pathway, thereby promoting OC differentiation. Consistent with this, mice lacking RelA/p65 in the hematopoietic compartment were shown to have a deficient osteoclastogenic response to RANKL and were protected from arthritis-induced osteolysis.     

Effect of administration of diethylcarbamazine on murine leukemia virus (Cas-Br-M) infected mice

Previous studies indicate that decreased serum viral infectivity and viral antigen levels follow oral administration of diethylcarbamazine (DEC) in feline leukemia virus infected cats, even though DEC has not been shown to exhibit in vitro antiviral activity. In this investigation, DEC was given by oral administration or (single dose) IP injection to murine leukemia virus (Cas-Br-M) inoculated mice to permit evaluation of its effect on viral-induced central nervous system disease. The survival of Cas-Br-M inoculated mice receiving DEC in water was significantly prolonged relative to similarly inoculated mice receiving distilled water. Among the Cas-Br-M inoculated mice euthanatized after the study, higher body weights and trend toward less severe brain and splenic lesions were noted in those receiving DEC in drinking water. Given these results, the possible utility of DEC in treatment of retroviral and other infections warrants further study.     

Diffusion-regularized susceptibility tensor imaging (DRSTI) of tissue microstructures in the human brain

Susceptibility tensor imaging (STI) has been proposed as an alternative to diffusion tensor imaging (DTI) for non-invasive in vivo characterization of brain tissue microstructure and white matter fiber architecture, potentially benefitting from its high spatial resolution. In spite of different biophysical mechanisms, animal studies have demonstrated white matter fiber directions measured using STI to be reasonably consistent with those from diffusion tensor imaging (DTI). However, human brain STI is hampered by its requirement of acquiring data at more than 10 head rotations and a complicated processing pipeline. In this paper, we propose a diffusion-regularized STI method (DRSTI) that employs a tensor spectral decomposition constraint to regularize the STI solution using the fiber directions estimated by DTI as a priori. We then explore the high-resolution DRSTI with MR phase images acquired at only 6 head orientations. Compared to other STI approaches, the DRSTI generated susceptibility tensor components, mean magnetic susceptibility (MMS), magnetic susceptibility anisotropy (MSA) and fiber direction maps with fewer artifacts, especially in regions with large susceptibility variations, and with less erroneous quantifications. In addition, the DRSTI method allows us to distinguish more structural features that could not be identified in DTI, especially in deep gray matters. DRSTI enables a more accurate susceptibility tensor estimation with a reduced number of sampling orientations, and achieves better tracking of fiber pathways than previous STI attempts on in vivo human brain.