鼻粘膜血流量的初步探索

为探索鼻粘膜微循环在病理生理学中的意义。第一阶段研究正常人及慢性鼻炎患者鼻粘膜微区血流量(NMBF),以期在微循环的基础上,为今后治疗鼻炎的研究工作奠定基础。本课题应用激光多普勒血流仪(PF_2)     

中药雾化吸入治疗慢性阻塞性肺病疗效观察与护理

目的 探讨中药雾化吸入在治疗慢性阻塞性肺病中的疗效,提高患者的生活质量.方法 选择慢性阻塞性肺病患者200例随机分为观察组和对照组,观察比较两组的疗效.结果 观察组采用无创中药雾化吸入治疗,有效率明显高于对照组,经χ2检验(P＜0.01)有显著统计学意义.结论 中药雾化吸入疗法是治疗慢性阻塞性肺病最简单、经济、有效的方法,应在临床上推广使用.     

微波治疗慢性过敏性鼻炎30例观察

目的 探讨微波治疗慢性过敏性鼻炎的效果。方法 对30例慢性过敏性鼻炎患者采用微波治疗。结果 术后每月复查1次，均随访观察1年，全部病例在术后次日，喷嚏、鼻痒、清涕等症状均获不同程度的改善，其中以鼻痒及喷嚏改善为明显。术后1次治愈25例，2次治愈2例，有效2例，无效1例；治愈率为90％，有效率为97％。结论 微波治疗安全性好，操作快捷，出血少，鼻粘膜损伤轻，是治疗慢性过敏性鼻炎的较好治疗方法。     

组胺激发试验对应变性鼻炎鼻粘膜微血管的影响

目的 研究组胺对应变性鼻患者鼻粘膜微血管的影响。方法 变应性鼻炎组28例，健康人组21例，用人体鼻粘膜微循环显微镜观察两组胺激发试验前后鼻粘膜微血管的管径、形态和管襻数的变化。结果 应变性鼻炎组组胺激发式试验后鼻粘膜微血管管径较激发前增粗，管襻数增加，鼻粘膜微血管形态以灯丝状以混合状增多。健康人组组胺激发试验前后鼻粘膜微血管管径、管襻数以形态均无变化。结论 变应性鼻粘膜微血管对组胺的反应性进行较健康人高，组胺对变应性鼻炎患者鼻粘膜容量血管和阻力血管均有舒张作用。     

雷诺氏综合征患者的微循环特点和中西结合治疗

对40例雷诺氏综合征（RDS）患者应用益气通阳活血化瘀中药与西药倍他乐克联合治疗，同时观察RDS患者治疗前后的甲襞微循环（NFM）、血液流变性和彩色多普勒血流显像（CDFI）变化。结果显示RDS患者经治疗后NFM明显改善，细动脉增宽、血流加快（P＜0．05），全血粘度、血浆粘度、纤维蛋白原及体外血栓重量与长度明显减轻缩小（P＜0．01）；CDFI表现动脉痉挛消失，血流阻力下降以及血流量增加。提示：益气通阳活血化瘀中药和倍他乐克西药合用有明显的降粘、解聚、抗栓、改善微循环的作用，治疗RDS有较好的疗效。     

针刺对经脉穴位微循环血流量的影响

目的:探讨针刺对经穴及非经穴微循环血流量的影响及其机制。方法:应用激光多普勒血流仪(LaserDopplerFlowmeter,LDF)检测30例健康人针刺前后十二经脉循经经穴、经穴旁开和在经非穴微循环血流量的变化。结果:人体穴位血流量高于经穴旁开和在经非穴(P<0.05);针刺时,十二经脉循经线上经穴的微循环血流量明显增加,经穴旁开的血流量增减不明显,两者相比有显著性差异(P<0.05);针刺时,十二经脉在经非穴的血流量虽有增加,但无统计学意义,经穴的血流量与在经非穴的血流量相比,具有显著性差异(P<0.05)。结论:经络的循经感传现象是可以客观检测的,微循环检测可以为经络的生理机制研究提供更多信息。     

高迁移率族蛋白B1在变应性鼻炎中的表达及意义

目的:探讨高迁移率族蛋白B1(HMGB1)在变应性鼻炎患者鼻甲粘膜中的表达及意义。方法:收集12例变应性鼻炎患者下鼻甲鼻粘膜及11例单纯性鼻中隔偏曲患者下鼻甲粘膜(对照组),采用免疫组化方法和RT-PCR方法检测下鼻甲粘膜中HMGB1的表达。结果:HMGB1表达水平在变应性鼻炎患者鼻甲粘膜中的表达水平较对照组明显增高(P0.01)。免疫组化显示阳性表达主要位于粘膜固有层间质,变应性鼻炎患者鼻甲粘膜中荧光强度明显高于对照组(P0.001),HMGB1 mRNA水平(5.0±1.2)与蛋白水平都和鼻甲粘膜中成熟的树突状细胞数目成正相关(r=0.695和r=0.578,P0.01),HMGB1蛋白水平与鼻甲粘膜中嗜酸性粒细胞数目(40.0±3.1)成明显负相关(r=-0.547,P0.01)。结论:HMGB1可能通过作用于嗜酸性粒细胞和树突状细胞抑制变应性鼻炎的发展。     

川芎嗪、当归注射液对急性微循环障碍大鼠血小板功能和器官血流量的影响

目的:从微循环、器官血流量和血液流变学角度,探讨川芎嗪、当归注射液对急性微循环障碍的干预作用。方法: 通过颈静脉注射高分子右旋糖酐(Dextran)复制大鼠急性微循环障碍模型,采用肠系膜微循环观察、器官微区血流和血液流变学测定方法,对18只大鼠进行研究。观察川芎嗪、当归注射液对急性微循环障碍转归时器官微区血流量、血小板功能的干预作用。结果:大鼠静脉注射Dextran后,出现了明显的微循环障碍,表现为微血管收缩、微血流变慢和微血栓形成,川芎嗪、当归注射液治疗后,微血流流态积分、微血栓积分、血小板粘附率和聚集率明显低于NS治疗组(p<0．05);川芎嗪、当归和NS组均能改善胃、肠、肝的微区血流量,但前者效果优于NS组(p<0．05)。结论: 川芎嗪、当归注射液通过改善微循环、降低血粘度和抑制血小板聚集和增加器官血流量,干预Dextran所致急性微循环障碍的转归过程。     

急性感染患者甲襞微循环的改变及中药912液的作用

目的 :观察急性感染患者甲襞微循环的变化特点及中药 912液对其影响。方法 :6 4例患者随机分成治疗组和对照组 ,治疗组加服中药 912液 2 0 0ml/日 ,对照组服温开水 2 0 0ml/日 ,共 7天。用XTW Ⅲ微循环检测仪观察其治疗前、后第 1、 3、 7天甲襞微循环的变化。结果 :急性感染患者的甲襞微循环 89.1%异常 ,其轻、中、重分别为 39.1%、 2 9.7%、 2 0 .3%。治疗前患者甲襞微循环血流速度明显减慢 ,流态积分明显增加 ,且与APACHE Ⅲ值呈明显相关 ,其值大于 30分时 ,形态与袢周积分也增高。治疗后 ,治疗组患者的血流速度明显加快 ,流态积分明显降低 ,其APACHE Ⅲ值明显降低 ,与对照组相比具有显著性差异。结论 :急性感染性患者末梢微循环以血流速度减慢和流态积分增高异常为主 ,且随病情加重而加重 ;中药 912液能明显改善急性感染患者微循环 ,改善患者病情     

糖肾安对早期糖尿病大鼠耳廓及肾脏微循环血流量的影响

目的:应用激光散斑成像(LSI)技术观察中药复方糖肾安煎剂对早期糖尿病(DM)大鼠耳廓及肾脏血流量的影响。方法:30只SD大鼠,采用高糖高脂饮食喂饲4周并一次性腹腔注射小剂量链脲佐菌素(STZ,35mg/kg)建立DM大鼠模型,将成模的28只大鼠随机分为DM模型组(n=9)、西药治疗组(胰激肽原酶肠溶片治疗,n=9)和中药治疗组(糖肾安煎剂治疗,n=10),另选10只SD大鼠作为正常对照组。药物治疗8周后,用moor FLPI-2全景激光灌注成像仪监测各组大鼠耳廓及肾脏微循环血流量变化。结果:DM模型组大鼠耳廓及肾脏血流量为133.42±49.58LSPU和297.19±39.43LSPU,正常对照组为70.04±7.28LSPU和239.27±33.27LSPU;中药治疗组为77.11±14.16LSPU和253.6±35.57LSPU,西药治疗组为82.71±14.03LSPU和248.96±39.26LSPU。DM模型组上述检测值均高于正常对照组(P0.01);中药治疗组和西药治疗组上述检测值均显著低于DM模型组(P0.01);中药治疗组、西药治疗组和正常对照组组间血流量差异无统计学意义(P0.05)。结论:糖肾安煎剂能明显减轻早期DM大鼠微循环障碍引起的微血管血流量增加,其效果与胰激肽原酶相当。     

Fluticasone propionate aqueous nasal spray reduces inflammatory cells in unchallenged allergic nasal mucosa: effects of single allergen challenge

BACKGROUND: Topical corticosteroid therapy reduces symptoms and nasal mucosal inflammatory cells in patients with allergic rhinitis. Usually patients are advised to start their medication (1 week) before the beginning of the pollen season. The effect of pretreatment with a topical corticosteroid on unchallenged nasal mucosa is not well documented. OBJECTIVES: The purpose of this study was to investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks' pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms and inflammatory cell numbers after nasal allergen provocation in patients with seasonal allergic rhinitis. METHODS: Nineteen patients with grass pollen-induced allergic rhinitis were treated for a 6-week period out of the grass pollen season. After completing the treatment period, patients were challenged with grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient. In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils, macrophages, and Langerhans' cells were investigated. RESULTS: After 4 weeks of treatment but before allergen provocation, significantly fewer epithelial Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found in the fluticasone propionate group compared with those found in the placebo group. In the lamina propria significantly fewer Langerhans' cells and eosinophils were found in the fluticasone propionate group. Cell influx in nasal mucosa after allergen provocation was significantly inhibited in the fluticasone propionate group compared with that in the placebo group for epithelial Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria eosinophils, mast cells, Langerhans' cells, macrophages, and T cells. CONCLUSIONS: Fluticasone propionate is effective in reducing early- and late-phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory cells in unchallenged nasal mucosa.     

Involvements of cysteinyl leukotrienes and nitric oxide in antigen-induced venodilatation of nasal mucosa in sensitized rats in vivo.

To determine an in vivo venodilatation of nasal mucosa, which is thought to be one of the causes of nasal obstruction in allergic rhinitis, venous diameters of nasal septa were directly measured in anesthetized rats. An application of antigen to nasal mucosa of sensitized rats caused an increase in diameters of mucosal veins, that is, venodilatation: the maximal response (about 20% increase in diameters) was observed at 55 min after antigen challenge. The antigen-induced increase in venous diameter of nasal mucosa was significantly inhibited by pretreatment with a cysteinyl leukotrienes (CysLTs) receptor antagonist, SR2640, and a nitric oxide (NO) synthase inhibitor, N(G)-monomethyl-L-arginine, indicating that CysLTs and NO might be involved in the venodilatation of nasal mucosa induced by antigen challenge. Blocking the action of CysLTs and NO might be therefore useful for the therapy of nasal obstruction in allergic rhinitis.     

Mucosal and systemic inflammatory changes in allergic rhinitis and asthma: a comparison between upper and lower airways

BACKGROUND: Local airway inflammation and airway remodelling are considered important in the clinical expression of allergic asthma. OBJECTIVE: The aim of this study was to compare airway inflammation and remodelling in nasal and bronchial mucosa of subjects with allergic rhinitis with or without asthma. METHODS: Four experimental groups were formed: allergic asthma and rhinitis (n = 19); allergic rhinitis, no asthma (n = 18); atopic subjects, no asthma, no rhinitis (n = 8) and non-allergic healthy control subjects (n = 16). Blood samples, nasal and bronchial biopsy specimens were collected during stable disease. Immunohistochemistry was performed for eosinophils (MBP), mast cells (CD117) and vascular endothelium (CD31). Epithelial loss, reticular basement membrane (RBM) thickness and subepithelial vascularity was assessed with a computer-assisted image analysis system. RESULTS: In nasal and bronchial mucosa, numbers of eosinophils were significantly higher in rhinitis patients with and without asthma than in asymptomatic atopics (P < 0.05) and controls (P < or = 0.01). In bronchial mucosa, the RBM was significantly thickened in rhinitis patients with and without asthma compared to asymptomatic atopics (P < 0.05) and controls (P < 0.01), while in nasal mucosa no differences were seen. Patients with asthma and rhinitis had increased numbers of blood eosinophils (P = 0.05) and skin test reactivity (P = 0.01) compared to patients with rhinitis only. No significant differences could be found between the investigated groups with respect to serum IL-5 and eotaxin levels, the number of mucosal mast cells and the degree of epithelial loss and subepithelial vascularity. Epithelial desquamation was significantly increased in the bronchial mucosa compared to nasal mucosa, not only in asthmatics (P < 0.001), but also in atopics without asthma and rhinitis (P = 0.02). CONCLUSIONS: This study shows that allergic inflammation, increased basement membrane thickness and epithelial desquamation are present in the lower airways of atopic subjects, even before the onset of clinical symptoms. Despite the presence of inflammatory cells, no structural changes could be assessed in nasal mucosa of allergic patients.     

IL-23 在变应性鼻炎小鼠模型中的作用及机制的研究

目的:探讨IL-23 在变应性鼻炎小鼠模型中的作用及机制的研究。方法:应用卵清蛋白(OVA)致敏建立小鼠变应性鼻炎模型,给予抗IL-23p19 单克隆抗体干预,计量抗原激发后小鼠搔鼻数量。应用HE 染色方法检测IL-23 对小鼠鼻黏膜炎症影响,应用ELISA 法检测小鼠灌洗液中IL-4、IFN-β及IL-17A 含量。应用PCR 方法检测鼻黏膜中FOXP3 的含量。结果:治疗后抗IL-23p19 抗体组小鼠搔鼻症状相对于抗体对照组明显减轻(P<0.05),与PBS 组比较,OVA 组小鼠鼻黏膜炎症细胞浸润明显(P<0.01),鼻腔灌洗液中嗜酸性粒细胞数明显升高(P<0.05);抗IL-23p19 抗体治疗后,小鼠鼻黏膜炎症细胞浸润显著降低(P<0.05),鼻腔灌洗液中嗜酸性粒细胞数明显降低(P<0.05);抗IL-23p19 抗体治疗后,IL-4 及IL-17A 含量较IgG 抗体对照组降低(P<0.05),IFN-β含量不变(P>0.05)。抗IL-23p19 抗体治疗后,FOXP3 含量较IgG 抗体对照组增高(P<0.05)。结论:抗IL-23p19 抗体可有效治疗小鼠变应性鼻炎,其机制可能是抑制Th17 细胞的增殖并且促进调节性T 细胞的功能。     

Elevated nasal mucosal G protein levels and histamine receptor affinity in a guinea pig model of nasal hyperresponsiveness

BACKGROUND: Nasal hyperresponsiveness is a common feature of allergic rhinitis, but the underlying mechanisms have yet to be elucidated. The effects of repeated antigen inhalation on the characteristics of histamine H(1) receptors and expression levels of heterotrimeric guanosine 5'-triphosphate-binding proteins in nasal mucosa were investigated to understand the mechanisms of the pathogenesis of nasal hyperresponsiveness in allergic rhinitis. METHODS: Male Hartley guinea pigs were sensitized by the inhalation of dinitrophenylated ovalbumin antigen (10 mg of protein/ml) and repeatedly challenged by inhaling aerosolized dinitrophenylated ovalbumin antigen for 3 weeks. Twenty-four hours after the last antigen inhalation, in vivo nasal responsiveness to histamine was measured. [(3)H]Mepyramine binding assays and immunoblotting for alpha subunits of the G(q) protein were also performed using membrane preparations of isolated nasal mucosae. RESULTS: The histamine-induced increase in intranasal pressure was significantly augmented after repeated antigen challenge, indicating that nasal hyperresponsiveness was achieved. In saturation binding studies, no significant change was observed in the density and antagonist affinity of H(1) receptors in the hyperresponsive animals. On the other hand, the affinity of histamine for high-affinity agonist binding sites in the hyperresponsive group, measured by histamine competition binding studies, was much greater than that in control animals, and these results were affected by guanosine 5'-O-(3-thiotriphosphate) in both groups. Moreover, Galpha(q) levels in nasal mucosal homogenates were significantly increased after repeated antigen challenge. CONCLUSIONS: Elevated G protein levels in nasal mucosa might induce an increased binding affinity of histamine to its receptors, resulting in an augmented nasal response to histamine, that is, nasal hyperresponsiveness, in guinea pigs.     

Objective assessments of allergic and nonallergic rhinitis in young children

Background:  Allergic and nonallergic rhinitis are common childhood disorders.
Objective:  To study nasal eosinophilia and nasal airway patency in young children with allergic and nonallergic rhinitis to assess the pathology behind such diagnoses.
Methods:  We investigated 255 children at six years of age from the Copenhagen Prospective Study on Asthma in Childhood birth cohort assessing rhinitis history, specific immunoglobulin E relevant to rhinitis symptoms, nasal eosinophilia and nasal airway patency by acoustic rhinometry before and after decongestion. Associations were studied in a multivariate graphical model corrected for gender, height and nasal steroid usage.
Results:  Allergic rhinitis was significantly and directly associated with irreversible nasal airway obstruction (reduced decongested nasal airway patency) ( P  =   0.004), whereas nonallergic rhinitis was not. Both allergic rhinitis ( P  =   0.000) and nonallergic rhinitis ( P  =   0.014) were directly and significantly associated with nasal eosinophilia, but this association was stronger for allergic rhinitis.
Conclusion:  Allergic rhinitis and nonallergic rhinitis are of different pathologies as suggested from their different associations not only to allergy but importantly also to irreversible nasal airway obstruction and eosinophilic inflammation. Allergic rhinitis was significantly associated with nasal eosinophilia and irreversible nasal airway obstruction suggesting chronic inflammation and structural remodeling of the nasal mucosa in children at the age of 6 years. Nonallergic rhinitis exhibited no change in the nasal airway patency, but some nasal mucosal eosinophilia albeit less than children with allergic rhinitis.     

Effects of topical treatment with H1 and H2 antagonists on clinical symptoms and nasal vascular reactions in patients with allergic rhinitis

Fifteen asymptomatic subjects with allergic rhinitis participated in a double-blind, randomized, crossover, placebo-controlled study. The subjects were pretreated intranasally with a single dose of a selective H1 receptor antagonist, levocabastine, and/or selective H2 receptor antagonist, ranitidine, prior to a nasal allergen challenge. The nasal symptoms obtained at the challenge were assessed using a scoring technique 15 min after the allergen exposure. The nasal airway resistance was determined twice prior to and once after the allergen challenge using anterior rhinomanometry. The nasal mucosal blood flow was determined before and 15 min after allergen challenge using the 133Xe wash-out technique. After pretreatment with the H1 antagonist there was a statistically significant reduction in the number of sneezes and rhinorrhea compared to pretreatment with placebo. Pretreatment with the H2 receptor significantly decreased the rhinorrhea but not the sneeze. The nasal blockage was unaffected by both the H1 and the H2 antagonists. Pretreatment with the H1 and/or the H2 antagonists inhibited the reduction in the nasal mucosal blood flow induced by the allergen challenge to a significant degree. The present findings suggest that topical treatment with the highly selective histamine antagonist, levocabastine, inhibits allergen-induced reflex-mediated symptoms. H1 and H2 receptors do not appear to be involved in the regulation of the tone of the capacitance vessels. This indicates that a more complex mechanism participates in the induction of nasal blockage than the direct effect of histamine on H1 and H2 receptors on the capacitance vessels of the nasal mucosa alone. Both H1 and H2 receptors are of importance for the regulation of nasal mucosal blood flow during the allergic reaction.     

Effects of NIC,receptor antagonists on vasodilation induced by chemical and electrical activation of sensory C–fibre afferents in different organs

The effects of the non–peptide NK, receptor antagonists, CP96,345 and RP–67,580, were investigated in a model using anaesthetized pigs. Both the blood flow in the internal maxillary and the bronchial artery (ultrasonic flowmetry) and the superficial blood flow in nasal mucosa and the skin (laser–Doppler flowmetry) were monitored simultaneously. Vasodilation induced by substance P administered i.v. systemically was blocked by pretreatment with CP–96,345, 3 mg kg¹ but not by RP–67,580. CP–96,345 had no effects on the vasodilationo induced by calcitonin gene–related peptide or vasoactive intestinal polypeptide. The capsaicin–induced vasodilation in the superficial blood flow of the nasal mucosa and the skin, was reduced after the CP–96,345 pretreatment. The vasodilation induced by capsaicin infusion in the internal maxillary or the bronchial artery was not affected by the CP–96,345 pretreatment. Electrical stimulation of the vagal nerve induced a vasodilation in the bronchial circulation which was not attenuated by pretreatment with CP–96,345. In the nasal mucosa and the skin NK₁ receptors seem to be involved in the vasodilation in the superficial small vessels, due to chemical activation of sensory C–fibre afferents. Furthermore, CP–96,345 is a useful tool in the evaluation of NK_X receptor–mediated responses. RP–67,580 which has been shown to have NK₁ antagonistic properties in the rat has no such effects in the domestic pig.     

Montelukast plus cetirizine in the prophylactic treatment of seasonal allergic rhinitis: influence on clinical symptoms and nasal allergic inflammation

BACKGROUND: The aim of our study was to investigate effects of 6-week pretreatment of seasonal allergic rhinitis (AR) with cetirizine, and montelukast, alone and in combination. Antihistamine/antileukotriene treatment is effective in AR. Antihistamines may prevent AR symptoms while prophylactic activity of antileukotrienes remains unclear. METHODS: Sixty AR patients, aged 18-35 years, were randomized to receive placebo, montelukast only, cetirizine only, or montelukast plus cetirizine, 6 weeks prior and 6 weeks after the beginning of grass pollen season. Mean self-recorded in-season symptom scores and mean weekly all-symptom scores were analyzed. In 31 patients, nasal lavages were performed before treatment, and at the end of the study, i.e. 12 weeks after the treatment initiation. Eosinophil and basophil counts, eosinophil cationic protein (ECP), and mast cell tryptase (MCT) levels were evaluated in lavage samples. RESULTS: Combined montelukast/cetirizine pretreatment significantly reduced in-season symptom score for sneezing, eye itching, nasal itching, rhinorrhea, and congestion. Montelukast plus cetirizine were more effective than cetirizine alone in preventing eye itching, rhinorrhea, and nasal itching. Moreover, combined pretreatment with montelukast and cetirizine delayed appearance of AR symptoms. Eosinophil nasal lavage fluid counts were significantly increased during pollen season in placebo and montelukast-only groups. No differences were observed in basophil counts. The in-season ECP level was significantly increased in all groups except montelukast-plus-cetirizine group. In-season MCT levels were not increased. CONCLUSION: Combined antihistamine and antileukotriene treatment started 6 weeks before the pollen season is effective in preventing AR symptoms and reduces allergic inflammation in nasal mucosa during natural allergen exposure.     

Vascular effects of slow reacting substance (SRS) in the cat nasal mucosa and the appearance of a SRS-like principle in cat nasal secretion on nerve stimulation

Stimulation of parasympathetic secreto-vasomotor nerve fibres in cat nasal mucosa produced nasal secretions with biological activity similar to cat paw SRS. The biologically active principle was purified by ethanol extraction, Amberlite XAD-2 and anion exchange chromatography. It had elution characteristics common with cat paw SRS but different to those of prostaglandin F_2α. The biological activity on the guinea pig ileum was antagonized by FPL 55712. In the cat intraarterial administration of cat paw SRS resulted in a dose-dependent but modest increase in nasal blood flow whereas local blood content was not affected. Provided SRS has similar effects on human nasal blood flow the importance for SRS as a mediator for nasal congestion in allergic rhinitis or parasympathetically induced vasomotor rhinitis seems less likely.