臀上皮神经临床意义

目的:阐明臀上皮神经临床意义。方法:解剖20具尸体(40侧)腰臀区,对臀上皮神经及相关结构进行解剖、观察、分析。结果:40侧腰臀区共发现138支臀上皮神经。在神经出胸腰筋膜后层处的卵圆形空隙有27个,其剩余空间周围见有脂肪组织。结论:臀上皮神经穿出胸腰筋膜后层处的卵圆形空隙为引起脂肪组织疝出、卡压神经引发腰痛的薄弱点。     

Immunohistochemical analysis of the vimentin filaments in Sertoli cells is a powerful tool for the prediction of spermatogenic dysfunction

The close interaction between male germ cells and Sertoli cells, a type of somatic cell found in the seminiferous tubules of mammalian testis, is essential for the normal progression of spermatogenesis in mammals. Vimentin is an intermediate filament protein that primarily provides mechanical support, preserves cell shape, and maintains the nuclear position, and it is often used as a marker to identify Sertoli cells. Vimentin is known to be involved in many diseases and aging processes; however, how vimentin is related to spermatogenic dysfunction and the associated functional changes is still unclear. In a previous study, we reported that vitamin E deficiency affected the testes, epididymis, and spermatozoa of mice, accelerating the progression of senescence. In this study, we focused on the Sertoli cell marker vimentin and explored the relationship between the cytoskeletal system of Sertoli cells and spermatogenic dysfunction using testis tissue sections that caused male reproductive dysfunction with vitamin E deficiency. The immunohistochemical analysis showed that the proportion of the vimentin-positive area in seminiferous tubule cross-sections was significantly increased in testis tissue sections of the vitamin E-deficient group compared with the proportion in the control group. The histological analysis of testis tissue sections from the vitamin E-deficient group showed that vimentin-positive Sertoli cells were greatly extended from the basement membrane, along with an increased abundance of vimentin. These findings suggest that vimentin may be a potential indicator for detecting spermatogenic dysfunction.     

炎症胶质细胞中诱导型一氧化氮合酶基因转录的机制

目的：通过瞬时转染p38MAPK途径中上游激酶，组成激活型MAPK激酶3和MAPK激酶6，进一步了解p38MAPK级联传导信号系统调节诱导型一氧化氮合酶基因在胶质细胞中的转录激活机制。 方法：实验于2003-01／2004-08在美国南卡洲医科大学神经科学研究室和南通大学基础医学院生物化学与分子生物学教研室进行。采用MAPK激酶3和MAPK激酶6表达质粒与接有荧光素酶的大鼠诱导型一氧化氮合酶启动基因质粒；cAMP反应元件和核因子-κB联合转染C6胶质细胞株。测定荧光素酶活性，观察诱导型一氧化氮合酶基因激活表达机制。 结果：①MKK3b／MKK6b能引起诱导型一氧化氮合酶启动基因质粒的激活，并都能够被p38MAPK抑制剂SB203580所抑制。②MKK可以诱导cAMP反应元件介导的和核因子-κB依赖的转录活性。③显性抑制型CRE结合蛋白和CCAAT／增强子结合蛋白都是p38MAPK的靶向作用目标，转染这两种转录因子产生相反的影响：显性抑制型CRE结合蛋白增强了诱导型一氧化氮合酶启动基因质粒的表达，而显性抑制型CCAAT／增强子结合蛋白则引起抑制作用，对cAMP反应元件也具有相同的影响。④此外，激活型MAPK激酶3和MAPK激酶6诱导诱导型一氧化氮合酶启动子的激活能够被野生型活化转录因子增强。然而磷酸化缺陷型的野生型活化转录因子则起抑制作用。 结论：转录因子的靶向作用特点，对于炎症反应中NO的过量产生具有选择干扰性，在临床上具有实用价值。     

Neuroprotective effects of Caralluma tuberculata on ameliorating cognitive impairment in a d-galactose-induced mouse model

Cognitive deficiency and oxidative stress have been well documented in aging disorders including Alzheimer’s disease. The aim of this study was to investigate the therapeutic efficacy of Caralluma tuberculata methanolic extract (CTME) on cognitive impairment in mice induced with d-galactose. In this study we assessed the therapeutic efficacy of CTME on cognitive impairment in mice induced with d-galactose by conduction of behavioral and cognitive performance tests. In order to explore the possible role of CTME against d-galactose-induced oxidative damages, various biochemical indicators were assessed. Chronic administration of d-galactose (150 mg/kg d, s.c.) for 7 weeks significantly impaired cognitive performance (in step-through passive, active avoidance test, Hole-Board test, Novel object recognition task and Morris water maze) and oxidative defense as compared to the control group. The results revealed that CTME treatment for two weeks (100, 200 and 300 mg/kg p.o) significantly ameliorated cognitive performance and oxidative defense. All groups of CTME enhanced the learning and memory ability in step-through passive, active avoidance test, Hole-Board test Novel object recognition task and Morris water maze. Furthermore, high and middle level of CTME (300 and 200 mg/kg p.o) significantly increased Total antioxidative capacity (T-AOC), Glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity, neprilysin (NEP), and β-site AβPP cleaving enzyme 1 (BACE1) expression while Nitric Oxide (NO), Nitric Oxide Synthase (NOS) activity and Malondialdehyde (MDA) concentration, and the level of Aβ1-42 and presenilin 1 (PS1) were decreased. The present study showed that CTME have a significant relieving effect on learning, memory and spontaneous activities in d-galactose-induced mice model, and ameliorates cognitive impairment and biochemical dysfunction in mice.     

4002/大鼠海马中83KD蛋白诱导神经干细胞向AChE阳性神经元定向分化的作用（英文）

背景：神经干细胞的临床应用还尚待时日,现阶段需要解决如何诱导神经干细胞分化为特定表型的神经元以替代丢失、变性的神经元细胞。 目的：探讨大鼠海马组织83 ku蛋白对神经干细胞向乙酰胆碱酯酶阳性神经元分化的作用。 设计、时间及地点：细胞学体外对照观察,于2003-10/2008-04在南通大学医学院完成。 材料：清洁级SD大鼠12只,17 d龄SD胎鼠多只,均由南通大学实验动物中心提供。 方法：取6只正常大鼠及6只切割海马伞后14 d大鼠的海马组织制成匀浆,进行非变性聚丙烯酰胺凝胶电泳,根据染色结果切取含有83 ku差异蛋白条带进行电洗脱,定量后调整蛋白浓度为300 mg/L。取胎鼠前脑组织,体外分离培养神经干细胞,设立3组：空白对照组加入单纯DMEM/F12无血清培养基;83 ku蛋白正常组、83 ku蛋白切割组分别加入含10 mg/L来自正常/割海马伞大鼠海马组织83 ku蛋白的DMEM/F12无血清培养基,诱导12 d。 主要观察指标：用乙酰胆碱酯酶组织化学染色检测神经干细胞分化为乙酰胆碱酯酶阳性神经元的情况。 结果：诱导12 d后,83 ku蛋白切割组乙酰胆碱酯酶阳性神经元较多,胞体大且分化较好,突起粗且长;83 ku蛋白正常组乙酰胆碱酯酶阳性神经元较少,胞体小,突起短;空白对照组仅见少量乙酰胆碱酯酶阳性神经元。组间乙酰胆碱酯酶阳性神经元数比较差异有显著性意义(P < 0.05),83 ku蛋白切割组>83 ku蛋白正常组>空白对照组。 结论：大鼠海马组织中83 ku蛋白可成功诱导神经干细胞定向分化为乙酰胆碱酯酶阳性神经元。     

MicroRNA-146a-5p attenuates neuropathic pain via suppressing TRAF6 signaling in the spinal cord

Glia-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. Our recent study demonstrated that TNF receptor associated factor-6 (TRAF6) is expressed in spinal astrocytes and contributes to the maintenance of spinal nerve ligation (SNL)-induced neuropathic pain. MicroRNA (miR)-146a is a key regulator of the innate immune response and was shown to target TRAF6 and reduce inflammation. In this study, we found that in cultured astrocytes, TNF-α, IL-1β, or lipopolysaccharide (LPS) induced rapid TRAF6 upregulation and delayed miR-146a-5p upregulation. In addition, miR-146a-5p mimic blocked LPS-induced TRAF6 upregulation, as well as LPS-induced c-Jun N-terminal kinase (JNK) activation and chemokine CCL2 expression in astrocytes. Notably, LPS incubation with astrocytes enhanced the DNA binding activity of AP-1 to the promoters of mir-146a and ccl2. TRAF6 siRNA or JNK inhibitor SP600125 significantly reduced LPS-induced miR-146a-5p increase in astrocytes. In vivo, intrathecal injection of TNF-α or LPS increased spinal TRAF6 expression. Pretreatment with miR-146a-5p mimic alleviated TNF-α- or LPS-induced mechanical allodynia and reduced TRAF6 expression. Finally, SNL induced miR-146a-5p upregulation in the spinal cord at 10 and 21 days. Intrathecal injection of miR-146a-5p mimic attenuated SNL-induced mechanical allodynia and decreased spinal TRAF6 expression. Taken together, the results suggest that (1) miR-146a-5p attenuates neuropathic pain partly through inhibition of TRAF6 and its downstream JNK/CCL2 signaling, (2) miR-146a-5p is increased by the activation of TRAF6/JNK pathway. Hence, miR-146a-5p may be a novel treatment for chronic neuropathic pain.     

Promotion of sciatic nerve regeneration in rats by a new neurotrophic pyrimidine derivative MS-430

• 1.1. The effects of a new neurotrophic pyrimidine derivative of MS-430 on nerve regeneration was examined using Wistar rats whose left sciatic nerve had been subjected to controlled injury.
• 2.2. The functional recovery and the packing density of common peroneal nerve axons were significantly enhanced with the administration of 3 mg/kg/day of MS-430.
• 3.3. These results suggest that MS-430 is a promising candidate as a neurotrophic drug for clinical use.

     

大鼠坐骨神经切断后Src抑制的蛋白激酶C的底物的表达变化

目的 探讨大鼠坐骨神经切断后,Src抑制的蛋白激酶C的底物(SSeCKS)在神经中的表达变化及其意义.方法 制备成年SD大鼠坐骨神经切断模型.通过Western blotting和免疫组织化学方法检测坐骨神经切断后SSeCKS表达的时空变化.结果 Western blotting显示,大鼠坐骨神经切断后,近端SSeCKS的表达逐步升高,伤后2d达到高峰,之后逐渐下降.远端SSeCKS表达于12h达到高峰,之后呈下降趋势.免疫组织化学方法结果表明,SSeCKS在神经断端处高表达,成簇状聚集;在远离断端处表达明显降低,分布亦较为均一.免疫荧光双标记结果显示,SSeCKS与S100、NF200及GAP43有部分共定位.结论 大鼠坐骨神经切断后,可以引起SSeCKS的表达变化,其可能参与周围神经损伤后某些伤害性刺激信号分子的转导,并与损伤后神经的再生及功能修复有关.