神经生长因子结构与功能研究进展

神经生长因子(NGF)是神经营养因子家族的典型代表, 它控制着脊椎动物周围和中枢神经系统中部分神经元的发育和存活.NGF的三维结构是以“胱氨酸结”和β折叠为基础,它以二聚体的形式结合细胞表面的受体从而发生生物学效应.参与这些反应的氨基酸残基已通过化学修饰和定点突变法加以确定,这有助于更进一步理解其结构与功能的关系.     

Theoretical Effect of Temperature on Threshold in the Hodgkin-Huxley Nerve Model

In the squid giant axon, Sjodin and Mullins (1958), using 1 msec duration pulses, found a decrease of threshold with increasing temperature, while Guttman (1962), using 100 msec pulses, found an increase. Both results are qualitatively predicted by the Hodgkin-Huxley model. The threshold vs. temperature curve varies so much with the assumptions made regarding the temperature-dependence of the membrane ionic conductances that quantitative comparison between theory and experiment is not yet possible. For very short pulses, increasing temperature has two effects. (1) At lower temperatures the decrease of relaxation time of Na activation (m) relative to the electrical (RC) relaxation time favors excitation and decreases threshold. (2) For higher temperatures, effect (1) saturates, but the decreasing relaxation times of Na inactivation (h) and K activation (n) factor accommodation and increased threshold. The result is a U-shaped threshold temperature curve. R. Guttman has obtained such U-shaped curves for 50 µsec pulses. Assuming higher ionic conductances decreases the electrical relaxation time and shifts the curve to the right along the temperature axis. Making the conductances increase with temperature flattens the curve. Using very long pulses favors effect (2) over (1) and makes threshold increase monotonically with temperature.     

Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration,Schwann Cell Function and Target Muscle Recovery

Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2–3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months.     

Effect of Sorbitol on Alpha-Crystallin Structure and Function

Biochemistry (Moscow) - Loss of eye lens transparency due to cataract is the leading cause of blindness all over the world. While aggregation of lens crystallins is the most common endpoint in...     

Effect of Weaning on Small Intestinal Structure and Function in the Piglet

Fifty-four piglets were selected from 12 litters weaned at 17 (Treatment 1), 21 (Treatment 2), 28 (Treatment 3) and 35 (Treatment 4) days old, respectively, to determine the effect of weaning age on small intestinal villus morphology, immunology and histochemistry. From proximal duodenum, proximal jejunum, distal jejunum and middle ileum, intestinal samples with three replicates (piglets) in each treatment were taken at 18, 22, 28 and 36; 22, 28, 36 and 43; 28, 36, 43, and 50; and 18, 22, 28, 36, 43 and 50d of age in Treatment 1, 2, 3 and 4, respectively. This was equivalent to 12h, 3d, 1 week, 2 week postweaning in Treatment 1; 12h, 1 week, 2 week, 3 week postweaning in Treatment 2 and 3, and all the same age in Treatment 4 as in Treatment 1, 2, 3, respectively. The results showed that villous height of duodenum and proximal jejunum decreased significantly in Treatment 1 and 3. Crypt depth in the duodenum, proximal jejunum and ileum also decreased significantly in Treatment 1. Date had significant effect on villous height of the duodenum, distal jejunum and ileum with the shortest on day 29 and crypt depth of all positions increased with piglet age except the crypt depth in proximal jejunum decreased on day 50. Weaning age and day of age had significant effects on intraepithelial lymphocyte (IEL) number and goblet cell (GC) number at all positions of small intestinal mucosa in piglets. The number of IEL at all segments of small intestinal mucosa in Treatment 3 increased significantly compared to those in other treatments, but IEL number at all locations of small intestinal mucosa in Treatment 2 decreased significantly compared to those in other treatments. The number of GC in small intestinal mucosa increased significantly in early-weaned (< day 21) piglets. It appears that providing fluid milk replacer for a few days postweaning could dramatically reduce the negative impact of weaning on villous morphology and digestive and absorptive function, especially in pigs weaned prior to 3 week of age. Finally, as weaning age was reduced, GC had a greater role in intestinal duct protection.     

缬沙坦对维持性血液透析患者心脏功能和结构的影响

目的:探讨缬沙坦对维持性血液透析(maintenance hemodialysis,MHD)患者心脏功能和结构的影响。方法:100例MHD患者,随机分为治疗组(50例)与对照组(50例),对照组仅予基础治疗,治疗组加予口服缬沙坦治疗,总疗程为6个月。观察治疗前后超声心动图指标变化。结果:与治疗前及对照组同期比较,治疗组心脏结构指标左房收缩末期内径(LAD)、左室舒张末期内径(LVDD)、室间隔厚度(IVST)、左室后壁厚度(LVPWT)、左房内径指数(LAI)、左室重量指数(LVMI)及相对室壁厚度(RWT)有所降低,心脏功能指标:左室射血分数(LVEF),左室短轴缩短率(FS),二尖瓣口舒张早期和晚期最大血流速度比(E/A)值有所提高,差异均有统计学意义(P<0.05)。对照组超声心动图各项指标与治疗前相比变化不明显(P>0.05)。结论:缬沙坦能延缓或逆转左心室肥厚,明显改善左室舒张功能,有助于改善MHD患者心脏重构,改善心脏功能,从而延缓慢性肾功能衰竭尿毒症期患者的左心室重塑,降低心血管疾病的发生率和死亡率。缬沙坦对MHD患者心血管疾病并发症的预防和治疗及提高MHD患者生存率有一定临床指导意义。     

Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays.     

不同解剖方法对面神经功能的影响

目的:通过比较腮腺手术中不同的面神经解剖,探讨其各自临床应用的利弊,为临床术式选择提供参考.方法:选择腮腺浅叶良性肿瘤或病变患者65例,随机采用颧支、下颌缘支、颊支的逆行解剖法或主干顺行解剖法解剖面神经,切除肿瘤.术后7d,观察面瘫发生情况和评估面神经损伤程度,并随访6个月.结果:顺行解剖组(主干解剖组)术后面瘫发病率(13.3%)低于下颌缘支组(60.0%)、颧支组(46.2%)和颊支组(41.7%).结论:在熟悉操作的前提下,采用面神经顺行解剖法可减少面瘫的发生.腮腺手术在面神经主干显露不受干扰的情况下,提倡采用顺行解剖法解剖面神经.     

电子束辐照对透明质酸功能及结构特性的影响

为了探讨电子束辐照对透明质酸功能及结构特性的影响,选择5、10、20、40、80 、100和150 kGy的电子束辐照固体透明质酸,测定透明质酸辐照前后分子量、特性粘度 、pH值、抗氧化性、紫外光谱、红外光谱、电镜图片的变化.结果表明,辐照降低透明 质酸的分子量、特性粘度、pH值;透明质酸在辐照前后的吸收特征峰没有显著的改变, 吸收强度增强;透明质酸形状随着辐照剂量的升高,由块状逐渐变成颗粒状;透明质酸 对DPPH·自由基的清除作用和还原力随着辐照剂量的增大逐渐增强.电子束辐照对透明 质酸分子结构和功能有一定的影响,但对其一级结构没有影响.     

尤瑞克林联合依达拉奉治疗房颤合并脑栓塞的疗效及对神经功能的影响

目的:分析尤瑞克林联合依达拉奉治疗房颤合并脑栓塞的疗效以及对神经功能的影响。方法:选取我院2013年1月至2015年1月收治的房颤合并脑栓塞患者220例,随机分为实验组与对照组,每组各110例。实验组患者采用尤瑞克林联合依达拉奉药物治疗,对照组采用低分子肝素治疗,记录治疗前后两组患者的凝血功能,对比两组患者的临床疗效,采用美国国立卫生研究院卒中量表(NIHSS)评价患者神经功能受损程度,日常生活活动能力量表(Barthel指数)评价患者的神经功能恢复情况。结果:治疗后两组患者的NIHSS评分较治疗前降低,且实验组明显低于对照组,Barthel指数较治疗前升高,且实验组明显高于对照组,差异均有统计学意义(P0.05);治疗后两组患者凝血酶时间(TT)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)、INR均显著高于治疗前,且实验组显著高于对照组,差异具有统计学意义(P0.05);治疗后实验组患者的总有效率为90.91%,显著高于对照组的60.09%,差异有统计学意义(P0.05)。结论:尤瑞克林联合依达拉奉治疗房颤合并脑栓塞疗效较好,可修复受损的神经系统,值得在临床上大力推广。     

New and Simple Test of Nerve Function in Hand

A simple objective test of innervation and regeneration of sensory nerves in the hand by immersion in warm water is described. The test results are shown to correpond to operation findings.     

Effect of Lycium Barbarum (Wolfberry) Polysaccharides on Preserving Retinal Function after Partial Optic Nerve Transection

Lycium Barbarum Polysaccharides (LBP) are the active components of Wolfberry (a traditional Chinese medicine) which has long been used for improving visual function. This study aims to investigate localized changes of retinal function in a partial optic nerve transection (PONT) model, and effects of LBP on visual function. The multifocal electroretinograms (mfERG) were obtained from 30 eyes of 30 Sprague-Dawley rats. The rats were divided into 6 groups (five treatment groups and one control group). Starting from the first day of the experiment, the rats in the (PONT+LBP) group and the (LBP) group were dosed with LBP; rats in the (PONT+PBS (phosphate buffered saline)) group and the (PBS) group were dosed with PBS via nasogastric tube every day until euthanized. The dorsal part of the optic nerve was transected in the (PONT), (PONT+LBP) and (PONT+PBS) groups at the end of week 1 (day 7 after LBP or PBS feeding began). The mfERG was measured at three time points: week 2, week 3 and week 5. Significant reduction of P1 and PhNR amplitudes of the mfERG were observed in all retinal regions a week after PONT. Feeding with LBP prior to PONT preserved retinal function. All mfERG responses returned to the normal range in the superior retina, which corresponds to the transected dorsal region of the optic nerve, while most of the inferior retinal responses were significantly increased at week 4 after PONT. The ventral part of the retina had secondary degeneration which was not only limited to the ganglion cell layer, but is a widespread effect affecting the outer retina. LBP altered the functional reduction caused by PONT by regulating the signal from the outer retina.     

异氟烷对化疗性大鼠异食癖恶心呕吐模型神经功能及呕吐相关神经递质的影响

摘要 目的：研究异氟烷预处理对化疗性大鼠异食癖恶心呕吐模型神经功能及呕吐相关神经递质的影响。方法：选用SD大鼠作为研究对象,腹腔注射顺铂以建立化疗性大鼠异食癖恶心呕吐模型（Model组）,腹腔注射等量生理研究作为对照组（Control）,在腹腔注射顺铂前1 h和12 h吸入异氟烷预处理作为异氟烷治疗组（Isoflurane）。记录腹腔注射顺铂0~12 h和12~24 h内各组大鼠摄入高岭土量;在腹腔注射顺铂0 h、12 h和24 h后,通过神经功能缺损评分法对各组大鼠神经功能进行评分;并在腹腔注射顺铂24 h后处死大鼠,收集大鼠回肠和延髓组织以检测5-羟色胺(5-Hydroxytryptamine,5-HT)、5-羟基-吲哚乙酸（5-hydroxy-indole acetic acid,5-HIAA）、色氨酸羟化酶（Tryptophan hydroxylase,TPH）以及单胺氧化酶（Monoamine oxidase,MAOA）含量。结果：与Control组相比,Model组和Isoflurane组大鼠在腹腔注射顺铂0~12 h,12~24 h以及0~24 h内摄入的高岭土量均显著升高（P<0.05）,并且Isoflurane组大鼠均显著Model组。三组大鼠在腹腔注射顺铂0 h、12 h和24 h后,神经功能评分均无显著差异（P>0.05）。与Control组大鼠相比,Model组和Isoflurane组大鼠在腹腔注射顺铂24 h后回肠/延髓组织内5-HT和TPH含量均显著升高,并且Isoflurane组大鼠显著低于Model组大鼠（P<0.05）;与Control组相比,Model组大鼠回肠和延髓组织中5-HIAA/5-HIT比值和MAOA含量均显著降低（P<0.05）;与Model组大鼠相比,Isoflurane组大鼠回肠5-HIAA含量、回肠/延髓5-HIAA/5-HT比值和MAOA含量均显著升高（P<0.05）。结论：异氟烷预处理可用于预防腹腔注射顺铂诱导的恶性呕吐,其机制可能与下降THP含量和提高MAOA含量,抑制5-HT合成以及促进5-HT代谢有关。     

神经生长因子药效学研究

目的考察神经生长因子对视神经损害的疗效。方法腹腔注射二硫化碳致视神经损害的大鼠模型,给药组球后注射或肌内注射神经生长因子,每天一次,每周6d,共计3周,空白对照组球后注射等量生理盐水,于治疗前后测定大鼠模式翻转（FREP）和闪光视觉诱发电位。结果球后注射高剂量组大鼠在治疗10d和20d时各波潜伏时比对照组有显著缩短,而球后注射低剂量组和肌内注射高剂量组大鼠于治疗10d时FVEP各波潜伏时也显著缩短,肌内注射低剂量组大鼠于治疗20d时FEP的P1和P2波潜伏时也显著或非常显著缩短。结论神经生长因子对大鼠视神经损害有明显的治疗作用。     

Brain-Derived Neurotrophic Factor Is More Highly Conserved in Structure and Function than Nerve Growth Factor During Vertebrate Evolution

Mammalian nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are members of a protein family with perfectly conserved domains arranged around the cysteine residues thought to stabilize an invariant three-dimensional scaffold in addition to distinct sequence motifs that convey different neuronal functions. To study their structural and functional conservation during evolution, we have compared NGF and BDNF from a lower vertebrate, the teleost fish Xiphophorus, with the mammalian homologues. Genomic clones encoding fish NGF and BDNF were isolated by cross-hybridization using probes from the cloned mammalian factors. Fish NGF and BDNF were expressed by means of recombinant vaccinia viruses, purified, and their neuronal survival specificities for different classes of neurons were found to mirror those of the mammalian factors. The half-maximal survival concentration for chick sensory neurons was 60 pg/ml for both fish and mammalian purified recombinant BDNF. However, the activity of recombinant fish NGF on both chick sensory and sympathetic neurons was 6 ng/ml, 75-fold lower than that of mouse NGF. The different functional conservation of NGF and BDNF is also reflected in their structures. The DNA-deduced amino acid sequences of processed mature fish NGF and BDNF showed, compared to mouse, 63% and 90% identity, respectively, indicating that NGF had reached an optimized structure later than BDNF. The retrograde extrapolation of these data indicates that NGF and BDNF evolved at strikingly different rates from a common ancestral gene about 600 million years ago. By RNA gel blot analysis NGF mRNA was detected during late embryonic development; BDNF was present in adult brain.     

苯肼对实验性脑疟模型DC亚群及功能的影响

探讨苯肼(Phenylhydrazine,PHZ)对实验性脑疟模型DC亚群及功能的影响。采用伯氏疟原虫(Plasmodium berghei ANKA,Pb ANKA)感染C57BL/6小鼠建立实验性脑疟模型,并在感染前第5天和感染第0天进行苯肼处理。动态监测小鼠网织红细胞数量、原虫血症和生存期;采用FACS检测感染后第3天和第5天小鼠脾脏中DC亚群(m DCs和p DCs)及相关功能分子(CD86、MHC II和IL-2)的变化水平。结果显示,PHZ处理能显著升高血液中网织红细胞比例,同时会升高小鼠原虫血症水平,缩短生存期;在感染后第3天和第5天,PHZ处理能促进Pb ANKA感染小鼠m DCs和p DCs的增殖分化,并能增强MHC II类分子和胞内IL-12的表达水平。PHZ引起的贫血能促进DCs的分化,同时促进功能分子的表达升高来启动适应型免疫应答,促进脑疟发生。     

Conduction Mechanisms in Lillie's Iron-Wire Model of Nerve

Based on theory and experiment, we found that the conduction through the oxide film in Lillie's iron-wire model is dominated by Schottky emission at low fields (below 10(6) v/cm), by electron tunneling from trap to trap at intermediate fields and by direct tunneling (Fowler-Nordheim type) at higher fields (above 3 x 10(6) v/cm). The trap-to-trap tunneling is considered to give rise to the negative resistance and the fixed position of the current maximum as observed. Some of the nervelike properties of the Lillie's model are interpreted on this tunneling mechanism.     

The Effect of Surgical Weight Reduction on Left Ventricular Structure and Function in Severe Obesity

The aim of this study was to examine the effect of surgical weight reduction on cardiac structure and function and to seek the determinants of these changes. Sixty‐six severely obese adults (BMI ≥35 kg/m²) who received bariatric surgery underwent echocardiographic examination before and 3 months after surgery. At 3 months after surgery, BMI and systolic blood pressure (BP) decreased (43.3 ± 6.3 to 34.1 ± 5.6 kg/m², P < 0.001, and 146 ± 12 to 130 ± 14 mm Hg, P < 0.001, respectively). In left ventricular (LV) geometry, the relative wall thickness (RWT) and LV mass index decreased significantly (0.43 ± 0.05 to 0.35 ± 0.05, P < 0.001, and 50 ± 11 to 39 ± 11 g/m^2.7, P < 0.001, respectively) without changes in chamber size. Multivariate analyses showed change in systolic BP to be an independent predictor for the changes in RWT and LV mass index. In myocardial performance, peak systolic mitral annular velocity and all diastolic indexes showed significant improvements. We concluded that LV hypertrophy and function improved rapidly after bariatric surgery in severely obese adults. BP reduction was the major determinant for the regression of LV hypertrophy in the early stage of surgical weight reduction.     

建立“人工面神经技术”恢复周围性面瘫兔的闭眼功能

目的:建立"人工面神经技术"以恢复单侧周围性面瘫兔的眼轮匝肌闭眼功能,为周围性面瘫提供一种新的治疗手段。方法:制备单侧周围性面瘫兔,建立健侧眼轮匝肌肌电信号采集、中枢信号处理模式识别、患侧电流刺激眼轮匝肌系统。当健侧眼轮匝肌采集的肌电信号经信号识别、提取以及电脑分析判断,符合其闭眼刺激阈值时,即对人工电刺激器发出指令,由刺激电极直接作用于患侧眼轮匝肌,引起眼睑完全闭合结果:以最小电流刺激患侧眼轮匝肌,引起眼睑完全闭合刺激方式为正负矩形波,电流强度为0.30～0.50mA。结论:利用可植入式微机电技术,在单侧周围性面瘫模型建立"人工面神经反射弧",恢复患侧眼轮匝肌闭眼收缩,可维持双侧闭眼功能的对称性和同步性。