BV2对MSC接受受损PC12上清刺激后神经营养功能影响的研究

目的：观察小胶质细胞（BV2）在骨髓基质细胞（MSC）接受受损PC12上清刺激后，对其神经营养功能的影响。方法：采用原代细胞培养法培养骨髓基质细胞（MSC），以BV2和PC12细胞株分别代表小胶质细胞和神经细胞进行传代培养，应用转移筛网进行BV2与MSC的共育，流式细胞术检测PC12凋亡，透射电镜下进行观察，ELISA检测培养上清中的神经营养因子。结果：小胶质细胞（BV2）和损伤PC12上清同时刺激MSC时，后者分泌的上清能显著降低受损PC12的凋亡数目。结论：小胶质细胞的存在有利于接受受损神经细胞上清刺激的MSC发挥神经营养及神经支持功能。     

胶质细胞源性神经营养因子基因修饰骨髓基质干细胞移植脑出血大鼠 神经营养因子的表达

背景：研究证实,细胞移植和神经营养因子相结合治疗脑损伤能促进大鼠神经功能的恢复。 目的：观察移植胶质细胞源性神经营养因子基因修饰的骨髓基质干细胞对大鼠脑出血后神经营养因子表达的影响。 方法：通过脑立体定位仪向SD大鼠脑尾壳核注射胶原酶和肝素建立脑出血动物模型,将48只模型鼠随机分为3组,骨髓基质干细胞组、胶质细胞源性神经营养因子/骨髓基质干细胞组和对照组于建模后第3天在脑出血部位分别移植骨髓基质干细胞、胶质细胞源性神经营养因子/骨髓基质干细胞以及生理盐水。 结果与结论：与对照组和骨髓基质干细胞组相比,胶质细胞源性神经营养因子/骨髓基质干细胞组大鼠神经功能恢复更好;与对照组相比,移植后1,2周其他2组各神经营养因子表达均显著增加(P < 0.05)。提示胶质细胞源性神经营养因子基因修饰的骨髓基质干细胞移植治疗脑出血大鼠比单纯骨髓基质干细胞有更好的神经保护作用。     

胶质细胞源的神经营养因子研究进展

胶质细胞源的神经营养因子（Ｇｌｉａｌｃｅｌｌｉｎｅ－ＤｅｒｖｅｄＮｅｕｒｏｔｒｏｐｈｉｃＦａｃｔｏｒ，ＧＤＮＦ），自发现以后，其分子结构和基因序列都已搞清楚，重组基因也已表达成功，同时针对其生物学作用和临床应用等方面也做了大量工作，至今已取得可喜进展。这里就ＧＤＮＦ的蛋白和分子结构作简要介绍，对人ＧＤＮＦ基因定位、鼠ＧＤＮＦ基因表达及调节、人ＧＤＮＦ基因表达，以及ＧＤＮＦ的作用方式等方面的研究工作做了综述     

辐射诱导神经炎症反应中小胶质细胞的活化机制

<正>肿瘤是严重危害人类健康的公共卫生问题。放射治疗是目前原发性或转移性脑肿瘤的主要治疗手段,可使脑肿瘤患者的远期生存率得到显著提高~([1])。然而,接受颅脑照射的患者中有90%会在治疗后6个月发生辐射相关认知功能障碍,这严重影响了患者的生存质量~([2])。辐射诱导认知障碍的发病机制比较复杂。研究发现,接受颅脑照射后可引起神经干细胞数量下降,神经干细胞再生能力、分化能力下降~([3]);也     

小胶质细胞与大脑发育和神经疾病

小胶质细胞是中枢神经系统中的巨噬细胞。在大脑的不同发育时期和不同病理生理状态，具有不同的形态和功能。既可以起到防御和促进神经元再生修复的作用，也可以介导病理损害的发生，与ＡＤ、ＭＳ、ＡＩＤＳ等大脑疾病密切相关。     

LPS激活的小胶质细胞提高损伤PC12存活率

目的 探讨激活小胶质细胞对损伤神经细胞存活的影响.方法 原代培养法及传代培养法分别培养小胶质细胞和PC12,以LPS激活小胶质细胞,PC12经纤维化Aβ1-40损伤后与小胶质细胞进行共育,流式细胞仪法检测PC12凋亡.结果 接受激活小胶质细胞共育的损伤PC12的存活率同对照组相比显著提高(P＜0.05).结论 在本实验环境下,LPS激活的小胶质细胞对PC12细胞具有营养功能.     

胶质细胞源性神经营养因子与脊髓再生

前　　言胶质细胞源性神经营养因子 (glial cell line- derivedneurotrophic factor,GDNF)是在 1993年由大鼠胶质瘤细胞系 B49中分离的糖基化的二硫键结合的同二聚体蛋白质 ,含有 134个氨基酸 ,分子量为 33～ 35 k D。因其具有 7个保守的半光氨酸残基 ,并且它们在分子出现的位置与转化生长因子- β(transform ing growth factor- β,TGF- β)超家族的全体成员均相同 ,所以 GDNF被认为是 TGF- β超家族的一员。人和大鼠的 GDNF基因业已被克隆 ,二者的氨基酸序列有 93%的同源性 [1 ] 。 GDNF的受体是多成分的复合物 ,它是由固定于质…     

胶质细胞系源性神经营养因子分子生物学的研究新进展

胶质细胞系源性神经营养因子属于转化生长因子β家族，由两条同源多肽链构成。ｃＤＮＡ长度有５８１ｂｐ和６５９ｂｐ两种，在神经组织和非神经组织中均有表达。ＧＤＮＦ对中脑多巴胺神经元和外周感觉，运动神经元的发育、存活和再生有较高的促进作用。     

胶质细胞源性神经营养因子受体

胶质细胞源性神经营养因子能够促进多种神经细胞特别是多巴胺能神经元及运动神经元存活。胶质细胞源性神经营养因子的信号传递受体是RET受体酪氨酸激酶,受体α亚基是它与RET相互作用的媒介。胶质细胞源性神经营养因子生物学活性的发挥需要RET与受体α亚基同时存在。     

胶质细胞株源性神经营养因子研究的新进展

1．前言胶质细胞株源性神经营养因子（Glialcellline－derivedneurotrophicfactor，GDNF）是多种神经元存活的必需因子。最初是由小鼠胶质细胞株B49细胞分离的精基化的二硫键结合的二体蛋白质，有134个氨基酸。它的7个半胱氨酸残基依其在分子中的配布位置与转化生长因子-β（transforminggrowthfactor-β，TGF-β）超家族成员分子相同，而且其序列中的＜20％为同源的，所以，GDNF为TG-β超家族的成员。最初鉴定的rhGDNF有促进大鼠胚胎中脑DA能神经元存活、形态分化和增强其摄取DA的能力，其EC50为1．2PM或36Pg／ml。但是，当其…     

Inducible expression of the signal transduction protein 14-3-3gamma in injured arteries and stimulated human vascular smooth muscle cells

Although the 14-3-3 family of proteins have been shown to be key signal transduction proteins involved in regulation of cellular growth and proliferation, little has been reported on their expression in pathophysiological states. We hypothesized that expression of one isoform, 14-3-3gamma, would also be increased in vascular proliferative diseases. We observed 14-3-3gamma expression induced in human coronary artery vasculopathy (CAV) as compared with coronary arteries isolated from normal and end-stage heart failure patients. 14-3-3gamma is acutely expressed in aortic medial smooth muscle cells in experimental models of arterial injury including rat cardiac allografts balloon angioplasty-injured swine coronary arteries. In each case, 14-3-3gamma protein expression is induced by 3 days and peaks at 7-10 days post-injury. Expression of this protein in cultured human vascular smooth muscle cells (VSMC) is associated with cytokine-induced VSMC activation, rather than direct injury to the VSMC themselves, and is unique among other 14-3-3 family proteins. Potential 14-3-3gamma protein-protein interactions are also differentially regulated by cytokine stimulation. This study indicates that 14-3-3gamma expression is induced in arterial trauma by cytokines, and suggests that this protein may play an important role in progression of vascular proliferative diseases.     

卡介菌多糖核酸对哮喘大鼠肺组织IL-12/STAT4信号通路的影响

目的探讨卡介菌多糖核酸(BCG-PSN)对支气管哮喘大鼠肺组织白介素12/信号转导子及转录激活子4(IL-12/STAT4)信号通路的影响及其在气道炎症中的作用。方法将40只雄性SD大鼠随机分成正常对照组(A组),哮喘模型组(B组),卡介菌多糖核酸组(C组)和地塞米松组(D组),每组10只。采用鸡清卵蛋白(OVA)致敏和激发的方法制备哮喘大鼠模型。苏木精-伊红(HE)染色观察肺组织病理形态学改变,用免疫组化法观察IL-12和STAT4在大鼠哮喘模型肺组织中的表达分布。结果模型组肺组织IL-12和STAT4蛋白表达较少,其平均灰度值显著高于对照组(P<0.01);地塞米松组和卡介菌多糖核酸组肺组织IL-12和STAT4蛋白表达较多,其平均灰度值显著低于哮喘组(P<0.01),而地塞米松组和卡介菌多糖核酸组之间差异无统计学意义;卡介菌多糖核酸组STAT4的表达与IL-12呈正相关(r为0.908,P<0.01)。结论卡介菌多糖核酸调节气道炎症可能是通过调控IL-12/STAT4信号通路的基因表达实现的。     

Altered thermal sensitivity in neurons injured by infraorbital nerve lesion

Nerve lesions are common injuries. While peripheral sensitivity is lost, the partially regenerating nerve undergoes a complex transformation, occasionally leading to persistent pain syndromes. Changes of thermal perception following nerve injury have received little attention. This study investigates the sensitivity of trigeminal neurons after infraorbital nerve lesion in guinea-pigs. Cultured trigeminal neurons innervating the area of denervation were identified by retrograde transport of DiI deposited at the site of the lesion. The standardized protocol consisted of cold and heat stimulation starting from body temperature as well as application of menthol and capsaicin, while activation was quantified by Fura-2-based calcium microfluorimetry. Compared to neurons from control animals, DiI-positive neurons were similar in the percentage and extend of the responses to menthol and capsaicin. However, DiI-positive neurons were less responsive to cold stimulation and had a lower cold threshold when compared to DiI-negative or control neurons. At the same time, DiI-positive neurons were more responsive to heat stimulation and had a lower heat threshold compared to control neurons. In summary, the percentage of trigeminal neurons responsive to thermal or chemical stimulation did not change after axotomy. However, thermal sensitivity of these neurons was altered.     

IL-6 cytokine family and signal transduction: a model of the cytokine system

The interleukin 6 (IL-6) cytokine family, which includes IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), ciliary neurotrophic factor (CNTF), IL-11 and cardiotrophin-1 (CT-1), exhibits pleiotropy and redundancy in biological activities. The IL-6 family cytokines exhibit a helical structure. Their receptors belong to the type 1 cytokine receptor family. The receptors of the IL-6 family cytokines share a receptor subunit, which explains one of the mechanisms of functional redundancy. In this review, we describe the general features of the IL-6 cytokine family and its signal transduction mechanisms. Many functional properties of the IL-6 family of cytokines and their receptors are general features of the cytokine system.     

Differentiation/maturation of neuropeptide Y neurons in the corpus callosum is promoted by brain-derived neurotrophic factor in mouse brain slice cultures

Neuropeptide Y (NPY) is widely distributed throughout both the central and peripheral nervous systems in mammals, and plays a role in various functions such as neural modifications affecting feeding, cardiovascular dynamics, or neural diseases. Many NPY neurons exist not only in gray matter in the central nervous system or ganglia in the peripheral system, but also in white matter such as the corpus callosum (cc) especially during development. The functions and regulation of callosal NPY neurons are not well understood, though NPY neurons in the cerebral cortex or hypothalamus are known to be regulated by neurotrophic factors such as brain-derived neurotrophic factor (BDNF). We examined the effect of BDNF on NPY neurons in the cc using organotypic slice cultures to clarify the regulation of callosal NPY neurons. A 3-week administration of BDNF significantly increased the number of NPY-immunopositive neuronal cell bodies and fibers in the cc rather than in the cerebral cortex as assessed with immunohistochemistry. Electron microscopy demonstrated that the NPY immunoreactivity mainly occurred in the regions associated with accumulating synaptic or cored vesicles. NPY-positive fibers had some contacts with several other neuronal fibers and glial processes. BDNF affected these fine structures of NPY neuronal fibers in the cc. These results suggest that BDNF takes part in the development, maturation, and maintenance of NPY neurons in the cc.     

酪氨酸蛋白激酶JAK1 在IL-6诱导JAK/STAT 途径活化中的作用

目的 酪氨酸蛋白激酶JAK1和转录因子STAT3为参与IL－6诱导的JAK／STAT信号转导途径的两种主要的信号蛋白分子。本研究试图揭示JAK1在JAK／STAT途径诱导活化中的作用。方法 分别采用凝胶阻滞电泳（EMSA）和免疫沉淀（IP）法观察IL－6刺激作用下STAT3和JAK1在3种骨髓瘤细胞系（XG－7，KM－3和Sko-007)中的诱导活化状态。采用RTPCR和Western-blot法检测这两种信号蛋白分子在以上3株靶细胞中的表达情况。结果 尽管SAT3在3株靶细胞中都能够正常表达，但只有Sko-007细胞中出现IL－6刺激作用下STAT3的诱导活化。在XG－7细胞中，既没有检测到JAK1的表达，也没有观察到JAK1的活化。尽管JAK1在KM－3细胞中能够正常表达，但不能被IL－6诱导激活。Sko-007细胞中则同时出现JAK1的表达及IL－6刺激后的诱导活化。结论 JAK1的正常表达和激活是IL－6刺激作用下JAK／STAT信号转导途径在骨髓瘤细胞中诱导活化的前提条件。