链霉素对于动物神经组织的毒性作用——组织化学研究

1.本实验选用听觉灵敏、平衡良好、体重在220—300克健康雄性豚鼠48只作慢性实验(实验25只、对照23只),8只雄性大鼠作急性实验(对照、实验各半)。慢性实验者每日一次肌肉内注射链霉素(硫酸盐),剂量为400毫克/公斤加葡萄糖酸钙,200毫克/公斤,100毫克/公斤。急性组一次肌肉内注射600毫克/公斤链霉素。 2.100毫克/公斤剂量者,连续注射任达一个月机能试验和组织化学检查均未见明显变化。400毫克/公斤+Ca及200毫克/公斤剂量者,实验动物平均在2个月左右眼震丧失,听力迟钝。但也有个别动物短在22天,长达158天才出现中毒症状者。 3.本实验对动物的桥脑和延脑进行了组织化学观察,结果表明,慢性中毒豚鼠耳蜗神经腹侧终核、前庭神经外侧终核、三叉神经起核内嫌色性细胞(即本实验中的Ⅲ型细胞)增多。SH基、蛋白质结合的组氨酸、酪氨酸、色氨酸、PAS反应、琥珀酸脱氢酶反应普遍减弱。碱性和酸性磷酸酶活性未见明显变化。 4.对急性和部分慢性中毒动物肋间肌运动终板乙酰胆碱酯酶进行了组织化学检查。急性中毒动物乙酰胆碱酯酶活性减弱,慢性中毒动物者未见明显变化。 5.实验证明:葡萄糖酸钙有解除动物的急性中毒和提高对链霉素耐受剂量的作用。 6.作者认为链霉素对中枢神经系的毒性作用是普遍的。本文对于一些结果进行了讨论。     

不同佐剂对IgD和IgE抗体产生的影响

作者使用不同佐剂,以探讨大鼠产生IgD和IgE的最佳方法。实验动物选用81只3月龄左右,体重250～350克的远系繁殖雄性Wistar大鼠。佐剂有Al(OH)_3、百日咳菌苗(半倍)Al(OH)_3(每2毫升含10~(10)百日咳杆菌和2.5毫克Al(OH)_3)和Freund氏完全佐剂(FCA)三种。抗原为卵蛋白.     

作为心包包囊层的一种新型生物膜

目前使用的心包包囊层材料是聚四氟乙烯(PTFE)薄膜,但未证实是一种理想的心包替代物,并且许多研究表明此种材料使用结果不十分理想。为了进一步发展新型理想的生物膜作为心包材料,作者评价了使用戊二醛处理的人羊膜(AM)作为心包替代物,并且与PTFE薄膜进行比较性研究。本研究的动物采用四只成年健康杂种狗,每只动物静脉内注射25mg/公斤戊巴比妥进行麻醉,再行右侧胸部造口     

激波管内挡板附近激波作用下狗胸腔不同部位的压力响应

通过外科手术将微型压力传感器放入狗胸腔内不同部位，在麻醉状态下置于ＢＳＴ—Ｉ型生物激波管内致伤。采用微机多路激波信号测试系统同步记录、分析了胸腔内不同部位的压力响应波形。得出了规则反射区内麻醉狗胸腔内不同部位的压力响应基本数据。主要结果如下：１左右胸腔、胸腔内不同部位的压力响应是有明显差异的。从活体动物试验的角度首次说明了胸腔内压力分布不均。２规则反射区中左、右胸腔（左侧为迎入射激波面，右侧为靠反射面一侧）的压力响应正压峰值显著高于体表压。左侧超压峰值比右侧高。右侧的压力上升速率快。由于胸内不同部位的压力差异较大，在以后的胸内压测定过程中，应注意到测试位置对结果的影响。在有关胸内压测量数据的比较、引用中也应注意到这一点     

聚四氟乙烯颗粒炎症反应性质的体内特征

据报道在1930年,聚四氟乙烯(PTFE)已开始用于尿道周围注射,治疗尿失禁,20年以后应用颗粒型PTFE作为实验选用材料,产生明显而令人满意的尿道下土丘,随后PTFE颗粒已成为有关泌尿系疾病治疗广泛认可的方法,但是很少知道关于注射部位及相关组织的长期形态学,所以本文作者进行了该项动物实验研究。采用三种动物,每组为杂种狗二只,New Zealand兔五只及10只BbLB/C鼠。将PTFE颗粒与甘油载体混合后分别注入每只动物体内,然后观察1周、3个月、6个月及1年。每只鼠背部皮下选择一个点,兔乳晕下选择二个点,狗乳晕下选择三个点和两处尿     

肾上腺素能药物对点燃大鼠海马CA_1区群集锋电位的影响

实验选用SD时雄性大鼠100只,50只实验组大鼠肌肉注射马桑内酯(1—1.25mg/kg),隔日一次),50只对照组大鼠肌注等容量的生理盐水。待动物出现前肢阵挛两天后和点燃达标7天后,分别与其相应的对照组间隔处死制备海马脑片。在CA_1区用细胞外记录群集锋电位(PS)的方法,观察滴加肾上腺素能受体激动剂至记录电极处的胞体层对点燃早期和点燃后的大鼠PS的影响。表明结     

激波管内挡板附近激波作用下狗胸廓表面的荷载过程

本实验应用自行研制的微机激波信号采集系统，同步多点采集了激波管内规则反射区中狗胸廓周围的压力分布，主要结果如下：１反射区中机体的荷载过程不同于自由场中机体的荷载过程。大致可分为三个阶段：（１）类似于自由场的一次绕流、拖曳荷载，方向与入射波一致；（２）由挡板反射回来产生的二次绕流、拖曳荷载，方向与入射激波方向相反；在这两个阶段中，体表不同部位的压力荷载有较大差异。（３）等压荷载阶段，机体不同部位受到的压力荷载大小基本一致，持续时间接近于自由场的相应阶段。这三个阶段中，一次及二次绕流、拖曳荷载的时间较短，仅为２～３ｍｓ。２规则反射区内，狗体表不同部位的荷载有显著的差异，特别是在一、二次绕流荷载、拖曳荷载的过程中。在冲击伤研究中应注意到这一点，以避免由于机体表面各点受激波压力均匀作用的假定可能带来的误差。由于不同部位的荷载差异，机体结构（如胸、腹壁）不同部位的动力学响应测试以及测试结果的解释也应注意到这一点     

狗失血性休克失代偿后进行声门外高频喷射通气的实验研究

12只杂种狗分成6组各2只。从股动脉放血至MAP5.3kPa后一直维持这一水平,根据贮血瓶内血液开始回灌和回灌最大失血量的30%将休克过程分为代偿期、失代偿期和不可逆期。实验组在失代偿后进行声门外高频喷射通气(HFXV)。进入不可逆期夹闭动脉停止血液回灌,再观察120min结束。实验结果:两组动物的代偿间期分别为     

戊巴比妥对大鼠骨胳肌辣根过氧化物酶的轴突摄取和逆行传送的作用

巴比妥药物对顺行轴浆运输方面的作用已有不少报道,而对逆行轴突传送方面却报道甚少。本工作观察了在正常剂量戊巴比妥钠的连续作用下,大鼠骨胳肌辣根过氧化物酶(HRP)的轴突摄取和逆行传送作用及其与不活动的关系。 实验是在体重为182克左右的43只雄性大白鼠进行,按实验要求分为下列七组。即神经组织中内源性过氧化物酶测定组。正常对照组,即动物在清醒状态下,腓肠肌内注射5毫克HRP(Sigma Ⅵ,R.Z=3—3.2)。     

血管紧张素Ⅱ对雄性大鼠下丘脑γ-谷氨酰转肽酶活性与GnRH含量的影响

近年来的研究表明，血管紧张素　（Ａｎｇ 　）能促进下丘脑促性腺激素释放激素（ＧｎＲＨ）的分泌。在人和动物的下丘脑组织中含有丰富的　一谷氨酰转肽酶（ＧＧＴ），其作用是促进氨基酸转运至细胞内，参与肽类或蛋白质的合成。本实验旨在观察雄性大鼠侧脑室注射不同剂量的 Ａｎｇ 　，下丘脑组织 ＧＧＴ活性与 ＧｎＲＨ含量的变化，以探讨两者间的关系。 实验选用成年Ｗｉｓｔａｒ雄性大鼠２０只，分为盐水对照组和脑室注射Ａｎｇ 　组：每只分别注射３０、 ６０及１２０ｎｇ／２０　Ｌ Ａｎｇ　。大鼠在乙醚麻醉下，按Ｐｅｌｌｅｇｒｉ…     

冲击波强度与幼年大鼠肺冲击伤程度的量效关系

目的:探索冲击波强度与幼年大鼠肺冲击伤程度的量效关系,为儿童冲击伤研究提供动物模型和基础。方法:选取20天龄幼年健康SD雄鼠40只,随机分为4组:BIG1、BIG2、BIG3和BIG4,每组各10只,采用BST-Ⅰ型生物激波管以4.8~5.8 MPa驱动压致伤,观察各组动物伤后生命体征、肺大体解剖和光镜病理等,并进行肺冲击伤严重程度评分。结果:幼鼠在驱动压致伤后均出现了不同程度的呼吸急促、心率加快的表现,外耳道出血发生率为57.5%（46/80）。肺大体解剖表现为不同程度的肺出血、水肿和肺不张等。光镜下病理主要表现为不同程度的肺出血、渗出、炎症细胞的浸润、肺间质水肿增厚、肺泡内水肿和肺泡壁的断裂等。4.8 MPa驱动压时,动物所受超压峰值为433 kPa,正向冲量14 226.4 kPa[?m,肺器官损伤定级（OIS）集中在Ⅱ、Ⅲ级（40%、30%）,肺冲击伤简明损伤定级（AIS）评分为0.90±0.57,损伤程度为轻度;5.0 MPa驱动压时,超压峰值为447.7 kPa,正向冲量14 463.5 kPa[?m,OIS多集中在Ⅲ级（60%）,AIS评分为1.60±0.69,损伤程度为中度;5.5 MPa驱动压时,超压峰值为484.7 kPa,正向冲量15 017.0 kPa[?m,OIS多集中在Ⅳ级（70%）,AIS评分为3.10±0.56,损伤程度为较重;5.8 MPa驱动压时,超压峰值为506.8 kPa, 正向冲量15 325.5 kPa[?m,OIS集中在Ⅴ级（40%）附近,AIS评分为4.00±0.67,肺损伤程度为重度。各组间损伤严重程度有明显统计学差异（P<0.05）。结论:利用BST-I型生物激波管,采用4.8~5.8 MPa高压段的驱动压可建立稳定的幼年SD鼠轻~重度肺冲击伤模型。幼年大鼠肺组织对冲击波损伤的耐受性强于成年大鼠肺组织,也强于幼年兔肺组织,其机制尚不太清楚,值得进一步深入研究。     

犬冲击伤早期血液流变学的变化

30只犬,用BST-Ⅰ型生物激波管致伤,以观察冲击伤早期血液流变学的变化。结果表明冲击伤早期有一过性的血液流变学改变,主要表现为血液粘度和血球压积升高、血小板粘附率增加,在伤后即刻随伤情加重而更为明显结果提示早期监测和及时处理血液流变学改变,对冲击伤的早期诊斷和救治可能有较重要的意义。     

Pathophysiology of battlefield associated traumatic brain injury

As more data is accumulated from Operation Iraqi Freedom and Operation Enduring Freedom (OEF in Afghanistan), it is becoming increasing evident that traumatic brain injury (TBI) is a serious and highly prevalent battle related injury. Although traditional TBIs such as closed head and penetrating occur in the modern battle space, the most common cause of modern battle related TBI is exposure to explosive blast. Many believe that explosive blast TBI is unique from the other forms of TBI. This is because the physical forces responsible for explosive blast TBI are different than those for closed head TBI and penetrating TBI. The unique force associated with explosive blast is the blast shock pressure wave. This shock wave occurs over a very short period, milliseconds, and has a specific profile known as the Freidlander curve. This pressure–time curve is characterized by an initial very rapid up-rise followed by a longer decay that reaches a negative inflection point before returning to baseline. This is important as the effect of this shock pressure on brain parenchyma is distinct. The diffuse interaction of the pressure wave with the brain leads to a complex cascade of events that affects neurons, axons, glia cells, and vasculature. It is only by properly studying this disease will meaningful therapies be realized.     

Altered gene expression in cultured microglia in response to simulated blast overpressure: Possible role of pulse duration

Blast overpressure has long been known to cause barotrauma to air-filled organs such as lung and middle ear. However, experience in Iraq and Afghanistan is revealing that individuals exposed to explosive munitions can also suffer traumatic brain injury (TBI) even in the absence of obvious external injury. The interaction of a blast shock wave with the brain in the intact cranial vault is extremely complex making it difficult to conclude that a blast wave interacts in a direct manner with the brain to cause injury. In an attempt to “isolate” the shock wave and test its primary effects on cells, we exposed cultured microglia to simulated blast overpressure in a barochamber. Overpressures ranging from 15 to 45 psi did not change microglial Cox-2 levels or TNF-α secretion nor did they cause cell damage. Microarray analysis revealed increases in expression of a number of microglial genes relating to immune function and inflammatory responses to include Saa3, Irg1, Fas and CxCl10. All changes in gene expression were dependent on pulse duration and were independent of pressure. These results indicate that microglia are mildly activated by blast overpressure and uncover a heretofore undocumented role for pulse duration in this process.     

Effect of melatonin on the functional recovery from experimental traumatic compression of the spinal cord

Spinal cord injury is an extremely severe condition with no available effective therapies. We examined the effect of melatonin on traumatic compression of the spinal cord. Sixty male adult Wistar rats were divided into three groups: sham-operated animals and animals with 35 and 50% spinal cord compression with a polycarbonate rod spacer. Each group was divided into two subgroups, each receiving an injection of vehicle or melatonin (2.5 mg/kg, intraperitoneal) 5 min prior to and 1, 2, 3, and 4 h after injury. Functional recovery was monitored weekly by the open-field test, the Basso, Beattie and Bresnahan locomotor scale and the inclined plane test. Histological changes of the spinal cord were examined 35 days after injury. Motor scores were progressively lower as spacer size increased according to the motor scale and inclined plane test evaluation at all times of assessment. The results of the two tests were correlated. The open-field test presented similar results with a less pronounced difference between the 35 and 50% compression groups. The injured groups presented functional recovery that was more evident in the first and second weeks. Animals receiving melatonin treatment presented more pronounced functional recovery than vehicle-treated animals as measured by the motor scale or inclined plane. NADPH-d histochemistry revealed integrity of the spinal cord thoracic segment in sham-operated animals and confirmed the severity of the lesion after spinal cord narrowing. The results obtained after experimental compression of the spinal cord support the hypothesis that melatonin may be considered for use in clinical practice because of its protective effect on the secondary wave of neuronal death following the primary wave after spinal cord injury.     

大鼠脊髓挤压伤后小胶质细胞Toll样受体4表达的变化

目的探讨脊髓挤压伤后各时间点小胶质细胞Toll样受体4(TLR4)的表达变化及其与损伤面积和免疫球蛋白G渗出范围的关系。方法 48只成年雄性SD大鼠建立T8节段脊髓挤压伤模型,随机分为6组,每组8只;假手术对照组及挤压伤组动物在手术后0h、3h、24h、72h和7d用4%多聚甲醛灌注固定,取以挤压点为中心的2cm脊髓,冷冻切片后进行HE染色和免疫荧光染色,分别观察损伤面积的变化,TLR4表达和TLR4阳性小胶质细胞的分布,以及与血浆免疫球蛋白G(IgG)渗出范围的比较,并用IPP6.0软件计算各组的阳性数目。结果脊髓损伤后TLR4主要表达在小胶质细胞,在3～24h之间开始表达,伤后在72h达到高峰,7d时已经显著下降。阳性小胶质细胞的分布与IgG渗出范围一致。结论大鼠脊髓挤压伤模型中,表达在脊髓小胶质细胞上的TLR4可在脊髓继发性损伤中发挥重要作用,并与血脊髓屏障开放有关。     

Brain Injuries from Blast

Traumatic brain injury (TBI) from blast produces a number of conundrums. This review focuses on five fundamental questions including: (1) What are the physical correlates for blast TBI in humans? (2) Why is there limited evidence of traditional pulmonary injury from blast in current military field epidemiology? (3) What are the primary blast brain injury mechanisms in humans? (4) If TBI can present with clinical symptoms similar to those of Post-Traumatic Stress Disorder (PTSD), how do we clinically differentiate blast TBI from PTSD and other psychiatric conditions? (5) How do we scale experimental animal models to human response? The preponderance of the evidence from a combination of clinical practice and experimental models suggests that blast TBI from direct blast exposure occurs on the modern battlefield. Progress has been made in establishing injury risk functions in terms of blast overpressure time histories, and there is strong experimental evidence in animal models that mild brain injuries occur at blast intensities that are similar to the pulmonary injury threshold. Enhanced thoracic protection from ballistic protective body armor likely plays a role in the occurrence of blast TBI by preventing lung injuries at blast intensities that could cause TBI. Principal areas of uncertainty include the need for a more comprehensive injury assessment for mild blast injuries in humans, an improved understanding of blast TBI pathophysiology of blast TBI in animal models and humans, the relationship between clinical manifestations of PTSD and mild TBI from blunt or blast trauma including possible synergistic effects, and scaling between animals models and human exposure to blasts in wartime and terrorist attacks. Experimental methodologies, including location of the animal model relative to the shock or blast source, should be carefully designed to provide a realistic blast experiment with conditions comparable to blasts on humans. If traditional blast scaling is appropriate between species, many reported rodent blast TBI experiments using air shock tubes have blast overpressure conditions that are similar to human long-duration nuclear blasts, not high explosive blasts.     

Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury

A weight drop model of brain injury was used to determine the effects of repetitive mild brain injury on motor function, heat shock protein and glial fibrillary acidic protein expression in the anesthetized, adult male, Sprague-Dawley rat. Repetitive mild brain injury was produced when animals received a series of three mild injuries spaced three days apart. A separate group of repetitive mild injured animals also received a subsequent severe brain injury between three and five days after the last mild injury. All animals were trained on a beam-walking test prior to surgery. The mild, repetitive mild and repetitive mild plus severe brain injury groups showed no motor deficits in the beam-walking test, whereas the animals with only severe brain injury showed significant motor deficits (increase in number of footslips) in the beam-walking test that recovered within eight days after injury. Both repetitive mild plus severe injury and severe injury only animals had cortical necrotic cavities of similar size in the region of the hindlimb motor cortex. Both the repetitive mild and severe brain-injured animals had marked heat shock protein 27kDa and glial fibrillary acidic protein staining in the cerebral cortex. Fluoro-Jade, heat shock protein 27kDa and 72kDa labeling indicated that there were widespread effects on cortical, subcortical and spinal neurons and glial cells after repetitive mild brain injury. These results suggest that repetitive mild brain injury conditions the brain so that subsequent brain injury at the same site has no effect on motor function. Furthermore, repetitive mild injury-induced activation of processes distant to the primary injury site may have a role in activation of secondary sites involved in recovery of motor function.     

冲击波致伤作用实验研究进展

原发冲击伤是爆炸产生的冲击波直接作用于生物体而引起的。各种生物激波管和其它冲击波发生装置的研制大大促进了冲击波致伤作用的实验研究的开展。通过将多种动物、离体器官以及培养的细胞暴露于冲击波,获得了大量的原发冲击伤实验研究结果。作者在简述冲击波的基本物理学特征的基础上,着重概括了生物激波管研制和原发冲击伤实验研究方法及其主要进展。