氨茶碱提高切断膈神经大鼠的通气

氨茶碱(AP)可兴奋呼吸.除了对呼吸中枢的作用外,同时亦影响呼吸肌的收缩性.以往曾报道AP 对膈肌的作用,本文观察其对切断膈神经大鼠吸气肌的作用.方法实验用Wistar 种雄性大鼠57只,体重260～320g.全麻后行气管切开术,接微型呼吸流速仪测定呼吸频率、潮气量、气管内压及最大吸气压.于颈部切断双侧膈神经.动物随机分为6组,其中5组静注AP,剂量每公斤分别为5、10、20、40和80mg,第6组静注等量生理盐水作为对照。于膈神     

慢性阻塞性肺疾病模型大鼠膈肌功能的实验研究

目的 以慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)模型大鼠为研究对象,探讨膈肌功能及短期控制性机械通气对膈肌功能的影响.方法 应用气管内滴注脂多糖联合被动吸烟的方法 复制大鼠COPD模型,比较正常大鼠与COPD大鼠跨膈压及膈肌肌电图频谱变化;对COPD模型组大鼠行短期控制机械通气,观察其膈肌功能的变化.结果 COPD模型组大鼠肺功能与正常对照组比较FEV0.3/FVC[(88.05±5.87)%vs(69.41±11.50)%]显著下降(P<0.05).COPD模型组大鼠跨膈压与正常对照组相比[(4.28±1.03)cm H2Ovs(5.36±0.94)cm H20]显著下降(P<0.05),说明COPD模型组大鼠呼吸肌力较正常对照组下降.COPD模型组大鼠较正常对照组大鼠的膈肌肌电高低频比值(%)(4.99±2.36 vs 3.12±1.10)下降显著(P<0.05),低频部分显著增加(P<0.05).COPD模型组大鼠机械通气(6 h)前后跨膈压及肌电图频谱分析结果 差异无统计学意义.结论 COPD模型组大鼠跨膈压较对照组减小,膈肌肌电图频谱分析高低频比值下降.说明其膈肌功能下降.短期(6 h)控制机械通气对COPD大鼠膈肌功能无显著影响.     

痰热清对慢性阻塞性肺疾病大鼠支气管上皮多药耐药相关蛋白1表达的影响

目的观察痰热清对慢性阻塞性肺疾病(COPD)大鼠支气管上皮多药耐药相关蛋白(MRP)1 mRNA的影响。方法雄性Wistar大鼠30只,随机分为COPD模型组、痰热清组和正常对照组,每组10只。除正常对照组,其余两组采用气管注脂多糖加熏香烟方法制备COPD模型,RT-PCR技术分析MRP1 mRNA基因表达。结果 COPD模型组和痰热清组大鼠支气管上皮细胞中MRP1的表达减少(P<0.01)。与模型组比较,痰热清组大鼠支气管上皮细胞中MRP1的表达增高(P<0.05)。结论痰热清注射液可能通过增高大鼠支气管上皮细胞中MRP1的表达而有效减轻COPD气道炎症,达到延缓COPD肺功能恶化和改善症状的效应。     

白介素15与慢性阻塞性肺疾病大鼠骨骼肌降解的相关性研究

目的 研究慢性阻塞性肺疾病(COPD)大鼠模型骨骼肌降解途径——泛素-蛋白酶体途径与白介素15(IL-15)的相关关系,为有效防治COPD患者骨骼肌蛋白高分解提供理论与依据.方法 成年雄性SD大鼠45只,分为模型组30只,健康组15只,采用反复熏香烟加气管内注入脂多糖法复制COPD大鼠动物模型.实时荧光定量PCR法和Western blot法分别检测大鼠膈肌、腓肠肌和肋间肌中E2-14K、MAFbx、Ub基因和蛋白表达.ELISA法检测大鼠血清、膈肌、腓肠和肋间肌中IL-15和肿瘤坏死因子α(TNF-α)的含量.结果 COPD模型大鼠膈肌、腓肠肌和肋间肌中E2 14K、MAFbx、Ub基因和蛋白表达分别较健康组升高.COPD模型组大鼠血清、膈肌、腓肠肌和肋间肌中IL-15、TNF-α的水平较健康组升高.大鼠血清、膈肌、腓肠肌和肋间肌中IL-15和TNF-α水平呈正相关(血清r=0.75;膈肌r =0.81;腓肠肌r=0.82;肋间肌r=0.78,P值均＜0.05).膈肌、腓肠肌和肋间肌中IL-15均与E2-14K、MAFbx、Ub相对表达量呈正相关(膈肌r=0.88、r=0.86、r=0.87;腓肠肌r=0.85、r=0.87、r=0.76;肋间肌r=0.85、r =0.80、r=0.84,P值均＜0.05).大鼠造模结束后体质量净增长与血清、膈肌、腓肠肌和肋间肌中IL-15呈负相关(血清r=-0.90,膈肌r=-0.85,腓肠肌r=-0.82,肋间肌r=-0.82,P＜0.05).结论 在COPD模型大鼠中,IL-15可能通过TNF-α共同作用于泛素-蛋白酶体途径影响骨骼肌降解的作用.     

辛伐他汀对COPD模型大鼠凋亡相关蛋白caspase-3的影响

目的探讨辛伐他汀对COPD模型大鼠肺组织凋亡相关蛋白caspse-3表达的影响。方法将30只大鼠随机分为正常组、对照组和治疗组,治疗组和对照组采用熏香烟加气管内滴入LPS法建立大鼠COPD模型,香烟暴露2周后治疗组给予辛伐他汀2.5 mg/kg治疗6周,正常组不作干预。8周后处死所有大鼠,HE染色观察大鼠肺组织病理改变,应用RT-PCR及免疫组织化学技术检测大鼠肺组织caspase-3基因及蛋白的表达。结果①肺组织病理学:对照组可见肺气肿和气道周围炎症性改变,治疗组肺气肿及气道周围炎症浸润较对照组减轻。②RT-PCR结果:与正常组相比,对照组和治疗组caspase-3 mRNA表达增多(P均<0.05);与对照组相比,治疗组caspase-3mRNA表达减少(P<0.05)。③免疫组化结果:与正常组相比,对照组和治疗组caspase-3表达增多(P均<0.05);与对照组相比,治疗组caspase-3表达减少(P<0.05)。结论辛伐他汀通过降低caspase-3基因及蛋白的表达,减少COPD大鼠肺组织细胞凋亡,在COPD中起到保护性作用。     

大鼠呼吸运动神经的分离和在体放电记录技术

目的建立一套简便易行的活体神经分离和神经放电记录技术。为进一步研究生理和病理条件下呼吸运动神经功能奠定基础。方法10只SD大鼠,350～450g,腹腔麻醉,颈部正中切口,于体视显微镜下分离同侧膈神经及舌下神经,分离并切断双侧迷走神经。用神经记录电极引导神经放电,多导生理仪记录放电,应用分析软件对结果进行分析。结果分别以臂丛和二腹肌后腹为标记点,可较顺利分离膈神经和舌下神经。记录60S,膈神经放电面积（36．3±3．2）μV．s,峰峰值（42．6±8．30）μV,最大值33．5μV,最小值-19．5μV;舌下神经放电面积（18．7±4．2）μV．S,峰峰值（33．6±9．30）μV,最大值27．9μV,最小值-22．0μV。结论鉴于大鼠神经分离和在体记录技术存在一定手术操作和记录技术的难度,呼吸运动神经功能研究受阻。为此,我们建立了一套简便易行的神经分离和在体神经记录方法,为研究呼吸运动神经放电奠定了基础。     

黄芩苷通过调节γ干扰素防治大鼠慢性阻塞性肺疾病

目的 制备慢性阻塞性肺疾病(COPD)大鼠模型,研究黄芩苷对其防治作用及可能机制.方法 成年雄性Wistar大鼠25只,分为空白组(F组),阳性对照组(C组),大、中、小剂量黄芩苷防治组(T1组、T2组、T3组),采用反复熏香烟加气管内两次灌注脂多糖的方法制备COPD大鼠模型,并于制备模型过程中进行干预.干预结束后处死...     

1,25-二羟维生素D3对慢性阻塞性肺疾病大鼠气道炎症的作用与机制

目的 研究1,25-二羟维生素D3[1,25(OH)2D3]对慢性阻塞性肺疾病(COPD)气道炎症的作用与机制.方法 雄性Wistar大鼠30只,分为对照组(A组)、COPD组(B组)和1,25(OH)2D3+COPD组(C组),每组10只,用熏香烟加气管注内毒素法建立大鼠COPD模型,在C组腹腔注射1,25(OH)2...     

慢性阻塞性肺疾病膈肌细胞凋亡的实验研究

目的观察烟雾和内毒素对大鼠膈肌细胞凋亡的影响,为探索COPD发生机制提供新的思路。方法 30只Wistar大鼠随机分为COPD组和对照组,采用烟雾暴露和气管内注入内毒素法建立COPD大鼠模型。第1、14、28天分别采集大鼠膈肌和肺组织标本,HE染色评估肺部病理改变,原位缺口末端标记法检测膈肌细胞凋亡,免疫组化法检测膈肌细胞Fas蛋白和半胱氨酸蛋白酶表达,RT-PCR测定Fas基因表达水平,第28天检测大鼠肺功能。结果第28天,COPD组大鼠的肺组织病理符合慢性支气管炎、肺气肿改变,肺功能均较对照组明显下降;第14、28天,COPD大鼠膈肌细胞凋亡率[（23.40±1.72）%和（34.60±1.25）%]明显高于对照大鼠[（1.04±0.10）%和（1.07±0.11）%],膈肌细胞Caspase-3表达、Fas蛋白及Fas基因表达COPD组也显著增高（P〈0.01）。结论在COPD的发生过程中存在膈肌细胞过度凋亡,Caspase-3和Fas/FasL途径参与了膈肌细胞凋亡的调控。     

PDTC对大鼠慢性阻塞性肺疾病血流动力学的影响

目的探讨NF-κB抑制剂吡咯烷二硫代氨基甲酸盐（PDTC）对慢性阻塞性肺病（COPD）各阶段的肺血流动力学及右心室壁厚度影响。方法将48只雄性SD大鼠随机分为八个组,分别纳入实验组及药物干预组,每组6只。实验组包括：A、B、C、D。正常对照组（A）：正常饲养4周;慢支组（B）：于实验第1、14天经气道内注入脂多糖（LPS）,200μg/次,4周后检测;COPD组（C）：第1、14天经气道内注入LPS,200μg/次,熏香烟1h/天,共4周;COPD并肺动脉高压组（D）：第1、14天经气道内注入LPS,200μg/次,熏香烟1h/天,共6周,实验的最后两周在熏香烟的同时,给予18%低氧8h/天。PDTC药物干预组为：A1（空白对照组）、B1（慢支干预组）、C1（COPD干预组）、D1（COPD并肺动脉高压干预组）。动物模型制作同各对应组,从第3周起给各药物干预组腹腔注射PDTC,剂量100mg·kg-1.d-1。A1组从第三周起腹腔注射同PDTC剂量相同的生理盐水。各组测定气道阻力、肺血流动力学和右心室肥厚指数,对肺组织行HE染色,观测气道的病理学改变,用免疫组化检测各组肺组织中NF-κB蛋白的表达。结果 C、D组RVSP、mPAP和RV/LV＋S都明显高于A组（P〈0.05）。C1、D1组RVSP、mPAP较C组、D组明显降低（P〈0.05）。D1组的RV/LV＋S值较D组有所降低（P〈0.05）。C、D组NF-κB蛋白表达强于A、B组（P〈0.05）,C1、D1组较实验组C、D组NF-κB蛋白含量下降。结论 COPD早期已出现肺血流动力学和右心室壁厚度的变化,PDTC干预后可抑制NF-κB蛋白表达,降低早期升高的平均肺动脉压力（mPAP）和右心室收缩压（RVSP）,减轻肺血管的重构,阻止右心室壁厚度的变化。     

Phrenic afferent input to the lateral medullary reticular formation of the cat

The afferent inputs from phrenic nerve stimulation to the lateral reticular formation of the lower brain stem were studied in anesthetized spontaneously breathing cats. The activity of reticular neurons was recorded by means of extracellular tungsten microelectrodes. Electrical stimulation of the central end of the right phrenic nerve evoked excitatory or inhibitory responses in the lateral reticular nucleus (LRN), in the nucleus ambiguus (AMB) and in a region dorsal to the AMB of ipsi- and contralateral sides. Phrenic afferents belonging to the flexor reflex afferent group were involved in these responses. The discharge pattern of the respiratory related units (RRU) of the AMB were exceptionally affected by phrenic nerve stimulations. It is concluded that high threshold phrenic afferents relay in the LRN before projecting to the cerebellar cortex. The overlapping of respiratory and non-respiratory afferents in the reticular formation may participate to the adaptations of respiratory and somatomotor functions during specific behaviors.     

Phrenic Nerve Conduction Abnormalities Correlate with Diaphragmatic Descent in Chronic Obstructive Pulmonary Disease

Diaphragmatic weakness in chronic obstructive pulmonary disease (COPD) is ascribed to hyperinflation-induced diaphragm shortening as well as impairment in cellular and subcellular structures. Although phrenic neuropathy is known to cause diaphragmatic weakness, phrenic neuropathy is rarely considered in COPD. This work aimed at assessing phrenic nerve conduction in COPD and its relation to radiographic hyperinflation and pulmonary function. Patients and methods: Forty COPD patients were evaluated. Radiographic parameters of lung hyperinflation were measured on postero-anterior and lateral chest x-ray films. Flow volume loop parameters were obtained from all patients. Motor conduction study of the phrenic nerves was performed and potentials were recorded over the xiphoid process and the ipsilateral 7th intercostal space. Twenty-seven healthy subjects were enrolled as controls. Results: Parameters of phrenic nerve conduction differed significantly in patients compared to controls. Phrenic nerve abnormalities were detected in 17 patients (42.5%). Electrophysiological measures correlated with diaphragmatic angle of depression on lateral view films and with lung height on postero-anterior films. They did not correlate with the flow volume loop data or disease severity score. Conclusion: Phrenic nerve conduction abnormality is an appreciated finding in COPD. Nerve stretching associated with diaphragmatic descent can be a suggested mechanism for nerve lesion. The presence of phrenic neuropathy may be an additional contributing factor to diaphragmatic dysfunction in COPD patients.     

Brainstem amino acid neurotransmitters and hypoxic ventilatory response

The ventilatory response to acute hypoxia in mammalian species is biphasic, an initial hyperventilatory response is followed by a reduction in ventilation within 2-3 min below the peak level (roll-off). Brain amino acid neurotransmitters also change during hypoxia. This study explores the role of neurotransmitters in anesthetized adult Sprague Dawley rats mechanically ventilated during 20 min of 10% O2 breathing. Phrenic nerve activity was recorded, and microdialysate concentrations of selected amino acids were determined at 3- to 5-min intervals in respiratory chemosensitive areas of the ventrolateral medulla (VMS) 1.25-2.00 mm below the surface. Phrenic nerve output was biphasic during hypoxia, concurrent with a rapid glutamate and gradual GABA increase. Taurine first decreased, then increased. In both intact and chemodenervated animals, time-dependent change in phrenic nerve activity during hypoxia was associated with corresponding changes in glutamate, GABA, and taurine concentrations, suggesting that cumulative effects of changes in the concentration of these three amino acids could account for response of the phrenic nerve to hypoxia.     

神经生长因子在慢性阻塞性肺疾病大鼠血、肺组织、支气管灌洗液中的表达

目的建立单纯香烟刺激诱导的慢性阻塞性肺疾病(COPD)大鼠模型,并观察神经生长因子(NGF)在香烟刺激COPD大鼠、戒烟1个月COPD大鼠中血、肺组织、支气管灌洗液中的表达变化。方法24只雄性SD大鼠,随机分为正常对照组、COPD组、戒烟1个月COPD组,采用6个月单纯香烟刺激建立COPD大鼠模型。通过观察肺组织病理变化、检测大鼠肺功能、对支气管肺泡灌洗液行分类计数评估COPD动物模型。并测定3组血、肺组织、支气管肺泡灌洗液中NGF蛋白、NGF mRNA表达。结果COPD组、戒烟1个月COPD组大鼠肺组织病理均显示肺气肿形成明显,相比正常对照组,肺顺应性和每分钟通气量均明显下降,气道阻力明显升高(均P<0.05)。COPD组、戒烟1个月COPD组支气管肺泡灌洗液的巨噬细胞总数显著多于正常对照组(P<0.05),但这两组之间差异无统计学意义(P>0.05)。3组血中NGF表达差异无统计学意义(P>0.05),COPD组、戒烟个1月COPD组肺组织、支气管肺泡灌洗液中NGF蛋白、NGF mRNA表达较正常对照组明显升高(均P<0.05),但这两组之间差异无统计学意义(P>0.05)。结论通过6个月单纯香烟刺激成功建立COPD大鼠模型,并且戒烟1个月后,停止造模干预,COPD病变仍持续存在。NGF持续性参与COPD的发生发展,即使戒烟,NGF仍参与肺局部炎症反应。     

Developmental aspects of the effect of naloxone on control of breathing in piglets

The respiratory effects of a stereospecific opiate antagonist, naloxone, were studied in two groups of paralyzed and vagotomized piglets who were servoventilated on 100% oxygen. Phrenic neural activity was used as the index of respiratory output. In 7 piglets less than 10 days of age naloxone infusion caused phrenic minute output to increase 122 +/- 36% (P less than 0.01). This change was accounted for by a significant increase only in peak phrenic activity, the neural equivalent of tidal volume. Frequency did not change significantly. In 7 piglets 20-34 days of age naloxone infusion caused phrenic minute output to increase 54 +/- 12% (P less than 0.025). Both peak phrenic activity and frequency were significantly increased. The increase in respiratory output observed in the younger piglets was significantly greater than that of the older piglets (P less than 0.05). These findings indicate that endogenous endorphins have a significant, though changing, role in control of breathing in the developing piglet.     

Phrenic nerve function in type 1 diabetic patients with diaphragm weakness and peripheral neuropathy.

Phrenic nerve latency was studied in 14 male type 1 diabetic patients with impaired diaphragm function and in 14 healthy control subjects. The diabetics showed significantly decreased values regarding inspiratory vital capacity and forced volume in 1 s compared with the control subjects. All other lung function parameters were similar in both groups. Although motor and sensory nerve conduction studies provided evidence for peripheral neuropathy in all patients, phrenic nerve latencies turned out to be normal. These results rule out a neuropathic disorder of the phrenic nerve. Thus, impaired diaphragm function in type 1 diabetic patients is not caused by phrenic neuropathy.     

Comparison of phrenic motoneuron activity in eupnea and apneusis

Our purpose was to characterize activities of phrenic motoneurons during apneusis. In decerebrate, cerebellectomized, vagotomized, paralyzed and ventilated cats, we recorded activities of phrenic nerve and single phrenic fibers during eupnea and apneusis. Reversible apneusis was obtained by cooling the rostral pons with a fork thermode. Phrenic motoneurons were defined as 'early' or 'late' during eupnea. Early units commenced activity before or during the first 20% of neural inspiration. The onset of discharge of late units extended throughout the rest of inspiration. In apneusis, some late units ceased activity entirely; others commenced activity at the end of the rising phase of phrenic activity or during the apneustic plateau. Early units commenced activities at the same time as in eupnea and generally maintained the same discharge frequency. Hence, the ramp phase of phrenic discharge in apneusis is generated largely by activities of early motoneurons. Our results imply that the level of bulbospinal activity impinging upon the phrenic nucleus is reduced in apneusis. The integration of efferent activity within the phrenic nucleus is discussed.     

Effects of Chronic and Acute Pulmonary Hyperinflation on Phrenic Nerve Conduction in Patients with COPD

Abstract

In patients with moderate-to-severe Chronic Obstructive Pulmonary Disorder (COPD), pulmonary hyperinflation can occur at rest and increase during episodes of exacerbation. Among other mechanical constraints, changes in position and configuration of the diaphragm are also induced by increased end-expiratory lung volume. Both descent and flattening of diaphragm might damage the phrenic nerves by stretching their fibers. The study aimed to investigate the phrenic nerve conduction in COPD patients in stable conditions and during COPD exacerbation. In a group of 11 COPD patients without relevant comorbidities in stable conditions and subsequently in another group of 10 COPD patients during in-hospital COPD exacerbation and recovery, measurements of functional respiratory parameters and assessment of phrenic nerves motor conduction by bilateral electric stimulation were performed concurrently. Significant increase in phrenic nerves latency (p?<?0.05), but similar amplitude of motor compound muscle action potential (cMAP) was observed in stable COPD patients vs. matched controls (p?<?0.05). However, in COPD patients with resting pulmonary hyperinflation as reliably detected by substantial Inspiratory Capacity reduction (<80% pred.), the mean bilateral latency was longer vs. COPD patients without pulmonary hyperinflation (p?<?0.02). During COPD exacerbation, in contrast with mean latency, the mean amplitude of phrenic nerves cMAP improved at discharge when compared with in-hospital admission (p?<?0.05). In stable COPD patients the velocity of phrenic nerve conduction was impaired mostly in the presence of pulmonary hyperinflation, while during COPD exacerbation where dynamic pulmonary hyperinflation abruptly occurs, the reversible decrease of cMAP amplitude does suggest a temporary, acute axonal damage of phrenic nerves, potentially contributing to diaphragmatic dysfunction in these circumstances.     

无创正压通气治疗慢性阻塞性肺疾病急性加重期患者呼吸肌疲劳的随机对照研究

目的 评价无创正压通气(NPPV)对慢性阻塞性肺疾病(COPD)急性加重期患者呼吸肌疲劳的影响.方法 采用前瞻性随机对照研究,将32例COPD患者随机分为Ⅰ组和Ⅱ组.Ⅰ组为常规治疗+NPPV,Ⅱ组仅接受常规治疗,观察2组治疗前后辅助呼吸肌动用评分、呼吸困难评分、肺功能、动脉血气、口腔闭合压和膈神经运动传导的变化.结果 治疗前2组患者均存在呼吸困难和辅助呼吸肌参与,口腔闭合压明显高于健康人,膈神经传导的潜伏期与健康人无显著差异,但动作电位的波幅明显低于健康人.治疗第8天,2组患者的症状均改善,Ⅰ组PaCO2降低了(31.0±17.6)mm Hg(1 mm Hg=0.133 kPa),与Ⅱ组比较,差异有统计学意义(P＜0.01).Ⅰ组患者肺功能亦显著改善,而Ⅱ组仅第1秒钟用力呼气容积有增加.Ⅰ组患者的口腔闭合压下降了(2.8±1.0)cm H2O(1 cm H2O=0.098 kPa),Ⅱ组仅下降了(0.3±0.5)cm H2O.Ⅰ组患者的膈神经动作电位的波幅亦较Ⅱ组显著增高.结论 COPD急性加重期患者治疗前均存在不同程度的呼吸肌疲劳,应用NPPV能改善气体交换,迅速缓解呼吸肌疲劳.     

Diaphragmatic dysfunction after open heart surgery: treatment with a rocking bed

Of 1225 patients undergoing open heart surgery over an 18-month period, 13 had diaphragmatic dysfunction due to phrenic nerve injury; 11 of these had internal mammary artery grafting. Nine had diaphragmatic dysfunction on the same side as the internal mammary artery graft side (7 bilateral and 2 unilateral) as determined by fluoroscopy during phrenic nerve stimulation. Although topical cardiac hypothermia has been the prevailing mechanism for diaphragmatic dysfunction due to phrenic nerve injury after open-heart surgery, dissection of the internal mammary artery with electrocautery, traction, or vascular compromise to the phrenic nerve, or a combination, could be additional factors. Rocking bed ventilation was instituted to facilitate passive diaphragmatic movement and airway decannulation and was continued at home until the phrenic nerve or nerves recovered. These patients were followed up clinically and with serial measurements of vital capacity, respiratory muscle strength, phrenic nerve latency, and fluoroscopy to determine recovery rate. Phrenic nerve recovery occurred from 4 to 27 months after surgery. This recovery was heralded by the patients' ability to assume the supine position without dyspnea when use of the rocking bed was discontinued. Unilateral diaphragmatic recovery was sufficient for the restoration of symptom-free supine posture.