脑源性神经营养因子在青光眼高眼压导致的视神经节细胞的凋亡抑制作用的研究概述

脑源性神经营养因子(brain-derived neurotrophic factor ,BD-NF)是神经营养因子家族中的一员 ,已有文献证实在脊髓损伤后BDNF具有抑制其神经元进一步凋亡的作用 ,并对坐骨神经、面神经等外周神经的损伤也具有显著的凋亡抑制作用 .而青光眼是世界范围内第二大致盲眼病 ,是由高眼压引起的视网膜神经节细胞的死亡 ,并最终致盲的严重眼科疾病.而目前为止 ,青光眼的发生机制仍然不明确.现今BDNF在视神经中的作用研究较少 ,而近年来国内外有文献报道称其对于损伤后的视神经节细胞进行性凋亡具有明显的抑制作用 .因此本文着重概述近年来BDNF在青光眼高眼压所致视神经节细胞损伤下的凋亡抑制作用的研究 ,为后续此方面的研究提供参考依据 .     

青光眼的视神经保护

青光眼是一种伴有视乳头损害和特征性视野缺损的神经病变。随着对青光眼病理机理的研究，尤其对青光眼性视功能丧失认识的不断深入，广大临床工作者已认识到青光眼视功能损害是多因素的，而非眼压升高单一因素，即在高眼压之外有着其他原发和/或继发的非压力依赖因素参与了青光眼视神经病变。而大量基础研究表明青光眼导致视功能损伤的病理基础是视网膜神经节细胞（RGC）进行性死亡和视神经纤维丢失，而RGC的死亡常导致视功能发生不可逆损害。如何阻止视网膜神经节细胞的死亡，保护视功能，达到治疗青光眼的最终目的，人们提出了青光眼的视神经保护概念，这也是青光眼领域研究的热点。     

青光眼与谷氨酸、细胞凋亡

青光眼是严重损害视力的常见眼病，其发病率为1％，一直是眼科工作的重点和难点。但目前对该病的病因和发生发展机制尚不十分清楚，长期以来人们对青光眼关注的唯一目标是眼压，并就眼压升高对视神经的损害提出两个学说：机械学说和血流学说。随着对青光眼神经损害机制研究的深入，发现兴奋性神经递质谷氨酸在视网膜神经节细胞损伤中起着重要作用，且神经节细胞是以凋亡的方式死亡的。本文就谷氨酸致视网膜神经节细胞凋亡及其可能的防治方法等方面进行综述。     

青光眼视神经损伤发病机制的研究进展

关于原发性青光眼的发病机制,目前有许多学说,但每种学说都不能完全说明青光眼视神经损害的具体机制。原发性青光眼进展的危险因素包括全身性及眼部因素,眼部因素包括眼压及非眼压因素。眼压虽然不是青光眼视神经损害的惟一因素,但仍然是青光眼最主要和最稳定的危险因素。另外,视网膜神经节细胞死亡是青光眼视神经损伤的最终共同通路,阻断视神经损伤通路和增强视神经存活机制的方法将成为一种重要的青光眼辅助治疗措施,目前这一领域主要包括抗凋亡途径、促红细胞生成素、抗青光眼药物等方面。     

青光眼神经保护的最新研究进展

青光眼是一组以特征性视神经萎缩和视野缺损为共同特征的疾病,目前是全世界第2位致盲性眼病.青光眼的发病机制还不十分明确,病理性眼压增高是其主要危险因素之一,此外,糖尿病、心血管疾病、近视、遗传、种族也是青光眼常见的危险因素[1].降低眼内压对视网膜神经节细胞(RGCs)及其轴突有神经保护作用,这种成功的治疗能延缓青光眼的发病或其病情进展.然而,有些病人在眼压降低后,仍会出现进行性视盘凹陷和视野缺损.据报道:大约1/7的病人在平均眼压控制在12.3mmHg的7年时间中出现进行性视野缺损.20%的病人在眼压下降了30%后的3～5年中病情仍在发展[2].此外,大约1/6出现青光眼损害的病人经反复测试并无高眼压的证据[3].很显然,仅靠降低眼压来达到神经保护的目的是不够的.因此,许多注意力已被放在青光眼视神经病的神经保护上,以保护RGCs及其轴突作为治疗策略.本文针对近几年文献,对青光眼神经保护方面的研究进展作一综述.     

针刺治疗青光眼研究进展

针刺降眼压有即刻效应和后效应,其机制可能不仅与改善房水排出、影响房水生成率有关,还与增加房水排出和血浆β-内啡肽浓度关。针刺保护视神经的机制可能与减少视网膜丙二醛的产生、增加超氧化物歧化酶和谷胱甘肽过氧化物酶、活化视网膜琥珀酸脱氢酶、提高视网膜三磷酸腺苷酶的活性、减轻视网膜超微结构的损害,降低高眼压状态后视网膜NO、葡萄糖含量、减轻视网膜超微结构损伤、增加视神经轴突的存活率、减少视网膜神经节细胞的凋亡、上调Bcl-xl、脑源性神经营养因子(brain derived neurotrophic factor,BDNF)表达有关。针刺能改善视网膜血流量、眼血流图波幅、灌注和排放指数,调节眼底的微循环。针灸治疗青光眼的效应主要体现在降低眼压、保护视神经、改善血流,其机制与影响相关机能调节和化学分子、神经递质表达有关。     

针刺治疗青光眼研究进展

针刺降眼压有即刻效应和后效应,其机制可能不仅与改善房水排出、影响房水生成率有关,还与增加房水排出和血浆β_内啡肽浓度关。针刺保护视神经的机制可能与减少视网膜丙二醛的产生、增加超氧化物歧化酶和谷胱甘肽过氧化物酶、活化视网膜琥珀酸脱氢酶、提高视网膜三磷酸腺苷酶的活性、减轻视网膜超微结构的损害,降低高眼压状态后视网膜NO、葡萄糖含量、减轻视网膜超微结构损伤、增加视神经轴突的存活率、减少视网膜神经节细胞的凋亡、上调Bcl_xl、脑源性神经营养因子（ brain de_rived neurotrophic factor,BDNF）表达有关。针刺能改善视网膜血流量、眼血流图波幅、灌注和排放指数,调节眼底的微循环。针灸治疗青光眼的效应主要体现在降低眼压、保护视神经、改善血流,其机制与影响相关机能调节和化学分子、神经递质表达有关。文献引用：刘志丹,杨森,朱蓓菁.针刺治疗青光眼研究进展[ J].中医学报,2015,30（1）：149-151.     

青光眼视网膜神经节细胞保护性治疗研究进展

青光眼是以进行性视神经损害和视野缺损为特征的致盲性眼病,它导致视功能损害的病理基础是视网膜神经节细胞(retinal ganglion cell,RGC)的进行性凋亡及视神经纤维的丢失.虽然目前还未完全明确青光眼的病理生理机制,但众多研究已经显示:高眼压和低血流灌注压所致的缺血、缺氧使视神经纤维轴浆运输中断,导致靶源性神经营养因子供给缺乏,造成对RGC的第1次打击(原发性损伤),继而产生过量的兴奋性氨基酸(EAA)如谷氨酸(GLU)及NO等,通过细胞表面NMDA(N-甲基-D-天门冬氨酸)受体及细胞内信号转导而激发一系列瀑布级联反应,激活某些凋亡诱导基因,最终导致DNA断裂、细胞凋亡,进一步造成对RGC的第2次打击(继发性损伤).随着基础研究的深入,可以预计加强RGC的保护性治疗,减慢或防止其凋亡,保持其生理功能,进而改善视功能将成为未来的青光眼治疗的又一重点.     

疏风解压明目汤联合西药治疗青光眼的临床研究

目的:探讨中药联合西药治疗青光眼的临床研究。方法:作者将多年临床中应用中药联合西药治疗青光眼的资料进行总结。结果:此疗法具有:改善神经供血,增强视网膜血管及视神经的耐氧能力,降低血液粘稠度,改善轴浆流,清除缺血后再灌注产生的氧自由基等功效。结论:a、降低眼压,减轻或防止因眼内压力的升高对眼组织造成的损害;b、保护视神经,通过药物治疗,起到对视网膜神经节细胞的保护作用,减少青光眼对视神经的损害。     

尼莫地平对慢性高眼压兔视神经损伤的保护作用

目的观察尼莫地平对慢性高眼压兔视神经的保护作用。方法 24只兔子随机分为正常组、治疗组、损伤组,治疗组每天给予尼莫地平灌胃。4周后观察视视网膜神经细胞形态及其凋亡情况。结果损伤组及治疗组凋亡细胞阳性率均高于正常组(P0.05);损伤组神经节细胞凋亡数量明显高于治疗组(P0.05)。结论尼莫地平(nimodipine NMD)做为钙离子通道阻滞剂(calcium channel blockers,CCB)对视网膜损伤有保护作用。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

The clinicopathological and immuohistochemical analysis of solid-pseudopapillary tumor of the pancreas： report of 9 cases

Objective：To investigate the clinical features, pathological characteristics and immunophenotype of solid-pseudopapillary tumor of the pancreas（SPTP）. Methods：Nine surgically treated cases of SPTP were retrospectively reviewed. Hematoxylin and Eosin（HE） staining and immunohistochemical staining were used to analyze all cases, and the general clinical data was collected. Results：Six patients were asymptomatic except for a palpable mass. Two patients complained of vague-epigastric pain. One patient appeared jaundice. The tumor was encapsulated and solid tissues alternately with cystic tissues. Histologically, the histological structure of solid portion was pseudopapillary with a fibrovascular core. Tumor cells were uniform and medium-sized which were arranged in sheets ets or nests or pseudopapillary patterns. Immunohistochemical studies demonstrated that SPTP proved positive in vimentin（9/9 cases）, AAT（9/9 cases）, NSE（9/9 cases）, ACT（7/9 cases）, CK20（2/9 cases）, CgA（1/9 cases）, S-100（3/gcases）, PR（4/gcases）, Syn（3/9 cases） and CD56（5/9cases）, negative in CEA and ER. Conclusion：SPTP is a tumor predominantly occurring in young women frequently without special symptoms. This tumor has various characteristical histological patterns with different immunophenotype.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.