The spatial cerebral damage caused by larger infarct and β-amyloid toxicity is driven by the anatomical/functional connectivity

Large cerebral infarctions are major predictors of death and severe disability from stroke. Conversely, data concerning these types of infarctions and the affected adjacent brain circuits are scarce. It remains to be determined if the co-morbid concurrence of large infarct and β-amyloid (Aβ) toxicity can precipitate the early development of dementia. Here, we described a dose-dependent effect of a unilateral striatal injection of vasoconstrictive endothelin-1 (ET-1) along with Aβ toxicity on CNS pathogenesis; driven by the anatomical and functional networks within a brain circuit. After 21 days of treatment, a high dose (60 pmol) of ET-1 (E60) alone caused the greatest increase in neuroinflammation, mainly in the ipsilateral striatum and distant regions with synaptic links to the striatal lesion such as white matter (subcortical white matter, corpus callosum, internal capsule, anterior commissure), gray matter (globus pallidus, thalamus), and cortices (cingulate, motor, somatosensory, entorhinal). The combined E60 + Aβ treatment also extended perturbation in the contralateral hemisphere of these rats, such as increased deposition of amyloid precursor protein fragments associated with the appearance of degenerating cells and the leakage of laminin from the basement membrane across a compromised blood–brain barrier. However, the cerebral damage induced by the 6 pmol ET-1 (E6), Aβ and E6 + Aβ rats was not detrimental enough to injure the complete network. The appreciation of the causal interactions among distinct anatomical units in the brain after ischemia and Aβ toxicity will help in the design of effective and alternative therapeutics that may disassociate the synergistic or additive association between the infarcts and Aβ toxicity.     

循经针刺对偏头痛的即刻疗效及其机制探讨

目的:观察循经针刺治疗偏头痛患者的即可疗效,并通过检测降钙素基因相关肽(CGRP)、血浆内皮素(ET)和五羟色胺(5-HT)的表达情况探讨其机制。方法:选取2017年2月至2018年2月天津中医药大学附属武清中医院收治的偏头痛患者85例作为研究对象,根据随机数字表法将患者分为观察组(n=43)和对照组(n=40),排除不良反应的5例,2组均为40例,观察组予以循经针刺法针刺少阳经的角孙、风池、外关、阳陵泉和丘墟穴,对照组予以非经非穴治疗。于治疗前及治疗后0. 5、1、2和4 h进行偏头痛积分和VAS(视觉模拟量表评分)评估;采用放射免疫法检测降钙素基因相关肽(CGRP)和血浆内皮素(ET),利用ELISA(酶联免疫吸附剂测定)检测五羟色胺(5-HT),观察2组患者治疗前和治疗后4 h的表达情况,探讨循经针刺的疗效机制。记录研究过程中存在的不良反应。结果:1)观察组循经针刺对偏头痛的临床有效率是90. 00%,对照组是67. 50%,观察组的临床有效率优于对照组,2组比较差异有统计学意义(P 0. 05)。2) 2组治疗后0. 5、1、2和4 h的偏头痛积分和VAS评分均较治疗前下降(P 0. 05),仅治疗后2 h及治疗后4 h的偏头痛积分和VAS评分较对照组低(P 0. 05)。3) 2组治疗前CGRP和ET的表达差异无统计学意义(P 0. 05);与治疗前比较,2组治疗4 h后均可下调CGRP和ET的表达水平(P 0. 05);观察组治疗后CGRP和ET的下调水平优于对照组(P 0. 05)。4) 2组治疗前5-HT的表达无比较,差异统计学异议(P 0. 05);与治疗前比较,2组治疗4 h后均上调5-HT的表达水平(P 0. 05),其中观察组优于对照组(P 0. 05)。5)研究过程中5例患者出现不良反应,其中观察组出现3例(晕针2例+局部出血1例),对照组2例(晕针1例+局部出血1例)。晕针患者平卧取针后即可恢复,局部出血则以局部按压进行止血处理。整个研究过程中均未出现严重不良反应。结论:循经针刺治疗偏头痛患者的即刻疗效于治疗后0. 5 h症状开始缓解,于治疗后4 h疗效最佳,其即刻疗效可能与上调CGRP和5-HT表达水平和下调ET表达水平有关。     

Effect of bosentan on leptin and endothelin‐1 concentration in plasma and brain after cardiac arrest in rats

In previous studies, bosentan was found to decrease plasma leptin concentrations after myocardial infarction (MI) in rats and had decreased mortality. The present study was undertaken to examine the effect of bosentan on leptin and endothelin‐1 (ET‐1) concentrations in plasma and ET‐1 concentrations in the hippocampus after cardiac arrest (CA) in rats. Studies were performed in 72 rats divided into treated and untreated animals in the following experimental groups: control, 3 min, 10 min, 1 h, 24 h, and 7 days after CA. Bosentan was given daily 2 h before CA or decapitation, 7 days, by gavage at a dose of 100 mg/kg. Plasma leptin concentration decreased in the early period after CA, and being elevated in 24 h, normalized 1 week later. Bosentan kept plasma leptin concentration at the control level in the postischemic period. Plasma ET‐1 concentration significantly increased during the postischemic period. Bosentan produced the elevation of plasma ET‐1 concentration in the preischemic period and kept the level of ET‐1 at control values after CA. Concentration of ET‐1 in the hippocampus was significantly lower 24 h after CA and was elevated after 1 week. The most dramatic effect of bosentan on ET‐1 concentration was in the hippocampus, where it significantly decreased during the entire postischemic recovery period. We postulate an important effect of bosentan on concentration of ET‐1 and leptin in plasma and ET‐1 in the brain after global cerebral ischemia caused by CA. Drug Dev Res 64:137–144, 2005. © 2005 Wiley‐Liss, Inc.     

疏血通注射液联合纳洛酮治疗慢性肺心病急性加重期的临床研究

目的 探讨疏血通注射液联合纳洛酮治疗慢性肺心病急性加重期对血浆内皮素（ET-1）的影响。方法 采用回顾性与便利抽样研究方法,病例收治时间为2010年2月—2016年12月,选择在此期间在西安市五环集团职工医院诊治的慢性肺心病急性加重期患者122例,按照治疗方法的区别分为观察组与对照组各61例,对照组给予纳洛酮治疗,2 mg加入0.9% NaCl注射液100 mL中静滴,1次/d。观察组在对照组治疗的基础上给予疏血通注射6 mL加入0.9% NaCl注射液100 mL中静滴,1次/d。两组都治疗观察28 d。比较两组疗效、三尖瓣区最大返流速度（V_max）和肺动脉压（PAPs）及ET-1水平,同时比较两组凝血功能指标。结果 对照组总有效率为86.9%,观察组为98.4%,观察组显著高于对照组（P<0.05）。治疗后两组的V_max值、PAPs值与血浆ET-1含量均显著低于治疗前（P<0.05）,且观察组显著低于对照组（P<0.05）。治疗后两组的凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）与凝血酶时间（TT）值都显著高于治疗前（P<0.05）,且治疗后观察组显著高于对照组（P<0.05）。结论 疏血通注射液联合纳洛酮治疗慢性肺心病急性加重期能抑制血浆ET-1的表达,改善肺动脉压力,具有抗凝的作用,从而有利于提高治疗疗效。     

清肝通窍汤联合声频共振治疗突发性聋42例

目的:观察清肝通窍汤联合声频共振治疗突发性聋的临床疗效。方法:选择本院2013年3月—2015年1月收治的突发性聋患者84例,按随机数字表法分为观察组与对照组,各42例。对照组给予舒血宁联合声频共振治疗,观察组在对照组治疗的基础上加用清肝通窍汤治疗。结果:观察组有效率为95.24%,对照组有效率为76.19%,观察组优于对照组(P0.05);观察组治疗后头痛眩晕、耳鸣、烦躁易怒、口苦咽干评分优于对照组(P0.05);观察组治疗1个疗程、2个疗程、4个疗程后血浆内皮素水平均优于对照组(P0.05);观察组不良反应发生率为4.76%,对照组不良反应发生率为7.12%,两组不良反应发生率比较,差异无统计学意义(P=0.6720.05);观察组复发率为2.38%(1/42),对照组复发率为7.14%(3/42),两组复发率比较,差异无统计学意义(P=0.6080.05)。结论:清肝通窍汤联合声频共振治疗突发性聋疗效显著,可有效改善患者内耳微循环及供血情况,缓解症状,降低血浆内皮素水平。     

口腔黏膜上皮癌变过程中内皮素Ⅰ表达的定量研究

目的 了解正常口腔黏膜,癌前病变及癌组织中内皮素I(ET-I)表达特点及其变化规律。方法采用免疫组化和图象分析技术,对人正常口腔黏膜(NOR)10例、口腔黏膜下纤维化(OSF)10例、鳞状细胞癌(SCC)15例上皮细胞的ET-I含量进行图像分析。结果 ①ET-I在OSF、OLK、SCC组织中的表达增强,阳性物质主要位于上皮棘细胞、基质细胞的胞浆胞膜上,且ET-I含量显著高于正常对照组(p<0.01)。②OLK、SCC上皮细胞ET-I含量呈显著增加趋势(p<0.05)。③OSF上皮细胞ET-I含量显著高于OLK(p<0.05),与SCC相比无显著性差异(p>0.05)。结论 ET-I含量在口腔癌前病变至癌变过程中可能存在一种量变关系,OSF中ET-I过量表达可能提示其上皮细胞的癌变潜能。     

高氧液对脑缺血大鼠内皮素及降钙素基因相关肽含量的影响

目的 :探讨高氧液对缺血大鼠脑细胞的保护作用。方法 :40只 Wistar大鼠 (雌雄各半 )随机分成高氧液组、对照组、模型组和假手术组 ,每组各 10只。阻断 3条动脉造成急性不完全性脑缺血 ,制备动物模型。制模成功后 ,高氧液组立即以 10 ml· kg- 1 · h- 1 的速率经尾静脉输入高氧液 ,对照组以同种方法输入等量生理盐水 ,模型组和假手术组不治疗。制模后 1小时各组动物经腹主静脉取血 ,然后立即断头取脑 ,测定内皮素 (ET)和降钙素基因相关肽 (CGRP)含量。结果 :高氧液可明显降低脑缺氧后 ET水平 ,而升高 CGRP水平 ,纠正 ET、CGRP失衡。结论 :高氧液对缺血大鼠脑细胞有明显保护作用。     

Involvement of Nax sodium channel in peripheral nerve regeneration via lactate signaling

Na_x, a sodium concentration‐sensitive sodium channel, is expressed in non‐myelinating Schwann cells of the adult peripheral nervous system, but the pathophysiological role remains unclear. We found that functional recovery of the hind paw responses from the sciatic nerve transection was delayed in Na_x knockout ( ) mice. Histological analyses showed a decrease in the number of regenerated myelinated axons in sciatic nerves. The delay in the recovery in mice was improved by lactate and inhibited by a monocarboxylate transporter inhibitor. In vitro experiments using cultured Schwann cells showed that lactate release was enhanced by endothelin (ET)‐1 and blocked by an ET receptor type B antagonist. Here, it is conceivable that Na_x was activated by ET‐1. The amount of lactate release by ET‐1 was lower in mice than in wild‐type mice. These results indicated that Na_x is functionally coupled to ET for lactate release via ET receptor type B and is involved in peripheral nerve regeneration.