组胺受体及抗组胺药的分类及其在变应性鼻炎中的应用

组胺是体内一种重要的化学介质,可通过活化H1、H2、H3、H4等类型受体参与多种病理生理过程.在变应性鼻炎(AR)的速发相中,肥大细胞脱颗粒释放组胺等炎性介质,组胺与鼻黏膜中H1受体结合触发喷嚏、鼻痒和流涕等症状,应用H1受体拮抗剂(H1RAs)可显著缓解上述症状.新近研究发现鼻黏膜中除H1受体外还存在H2、H3和H4...     

变应性鼻炎患者鼻黏膜中组胺H4受体的差异性表达

目的:观察新型组胺受体H4在正常人及变应性鼻炎患者鼻腔黏膜中的表达及分布, 初步了解组胺H4受体在变应性鼻炎发病中的作用.方法:选取正常健康者及变应性鼻炎患者各10例,取鼻黏膜分别通过免疫组织化学及RT-PCR方法检测组胺H4受体在蛋白质及转录水平的表达及分布情况并进行对比.结果:变应性鼻炎患者鼻黏膜中组胺H4受体的表达(49676±8541,0.69±0.11)较正常人(25509±6441,0.42±0.08) 显著增加(P<0.05),鼻黏膜结构细胞及免疫细胞均见H4受体表达.结论:H4受体存在于正常人鼻黏膜中,在变应性鼻炎患者鼻黏膜中表达显著增强,提示组胺H4受体可能是介导组胺参与变应性鼻炎发病的重要配体之一.     

正常人群鼻黏膜中组胺受体亚型的表达

目的 通过观察健康志愿者鼻黏膜中4种组胺受体(histamine receptor,HR)亚型的表达及分布差异,初步阐明4种HR亚型在正常人群鼻黏膜中的表达,为了解组胺(histame,HA)及其受体HR在鼻腔病理生理学中的作用提供理论基础.方法 选择健康志愿者10人,表面麻醉下取下鼻甲黏膜,分别行HR免疫组化检测及半...     

变应性鼻炎患者组胺受体表达及与嗜酸性粒细胞浸润相关性分析

目的 通过观察变应性鼻炎患者鼻黏膜中各种组胺受体亚型的表达及分布差异,初步阐明各种组胺受体在变应性鼻炎患者鼻黏膜中的表达,并与嗜酸性粒细胞浸润进行相关性分析,为了解组胺及其受体在变应性鼻炎病理生理学中的作用提供理论基础.方法 选择变应性鼻炎患者共10例,表麻下取下鼻甲黏膜,分别行组胺受体半定量RT-PCR检测以及嗜酸性粒细胞浸润程度评估.结果 半定量RT-PCR检测显示变应性鼻炎患者鼻黏膜中4种组胺受体均有表达,而且HR1表达显著高于HR2、HR3、HR4三种受体(P均<0.01),HR4表达显著高于HR2、HR3(P均<0.01),而HR2,HR3表达无显著差异(P>0.05).HR1,HR4与变应性鼻炎患者鼻黏膜中嗜酸性粒细胞浸润相关,其中HR4相关性相对较高,而HR2,HR3与其浸润无明显相关性.结论 变应性鼻炎患者鼻黏膜中四种组胺受体均有表达,其表达强弱顺序为HR1>HR4>HR2≈HR3.,HR1,HR4与变应性鼻炎患者鼻黏膜中嗜酸性粒细胞浸润相关.     

抗组胺药在变应性鼻炎中的应用

变应性鼻炎（AR）是特异性的个体接触变应原后由IgE介导的递质释放为开端,有多种免疫细胞和细胞因子参与的鼻黏膜的慢性炎性疾病。虽然AR的治疗方法和手段在不断更新,但抗组胺药常作为首选治疗方法。     

组胺H3受体激动剂IMETIT对豚鼠变应性鼻炎作用的初步探讨

目的:探索组胺H3受体激动剂(H3R激动剂)IMETIT对豚鼠变应性鼻炎(AR)模型的治疗作用和对P物质(SP)及其受体(SP-R)mRNA 表达的影响.方法:以OVA为致敏原,用豚鼠AR模型,观察症状及鼻黏膜病理状况以研究IMETIT对豚鼠AR 的治疗作用;免疫组织化学检测鼻中隔黏膜中SP含量,RT-PCR测定鼻中隔黏膜中SP-R mRNA 表达以研究IMETIT对SP/SP-R分泌及表达的影响.结果:组胺H3R激动剂IMETIT能有效改善豚鼠AR喷嚏(P＜0.01)、鼻痒(P＜0.01)、鼻塞(P＜0.05),减轻鼻黏膜病理性改变,调低SP/SP-R mRNA分泌及表达(P＜0.05或P＜0.01).结论:组胺H3R激动剂IMETIT能有效缓解豚鼠AR的症状,其作用机制与调低SP/SP-R 分泌及表达有关.     

左西替利嗪在变应性鼻炎治疗中的作用和地位

变应性鼻炎（AR）是特异性个体接触变应原后由IgE介导的鼻黏膜反应性炎性疾病。90％以上AR患者发生速发相反应（early-phasereaction,EPR）,表现为打喷嚏、疼痛、鼻痒、流涕和鼻塞。组胺是引起EPIR的主要炎性介质,通过结合组胺H1受体产生效应,与感觉神经元H1受体结合,在20N30s内迅速激发打喷嚏和鼻痒,约1min达高峰,10min后迅速下降。     

变应性鼻炎的特异性免疫治疗

变应性鼻炎（allergic rhinitis，AR）是特应性个体接触致敏原后由IgE介导的介质（主要是组胺）释放，并有多种免疫活性细胞和细胞因子等参与的鼻黏膜慢性炎症反应性疾病。AR的治疗原则包括变应原回避、药物治疗、免疫治疗以及对患者的宣教。毫无疑问，避免暴露于变应原是AR理想的防治措施，但通常难以做到。以第2代抗组胺药和鼻内皮质类固醇为主的药物治疗是目前临床上最常用的对症治疗方法，     

新2代抗组胺药在变应性鼻炎中的应用

组胺（histamine）是一种主要由肥大细胞及嗜碱性粒细胞分泌的小分子胺类。1910年Dale和LaidlawTM首次发现组胺是变应性炎症反应的重要介质。1940年后合成的最初抗组胺H1受体药物（H1antihistamines,以下简称抗组胺药）陆续上市,开创了抗组胺药治疗变应性疾病的先河。以后的70年里,大量临床实践及基础研究均证实组胺作为最主要的炎症介质直接参与了变应性鼻炎（AR）的速发相及迟发相反应,是AR的最核心介质。与此同时,抗组胺药也蓬勃发展,成为治疗I型变态反应性疾病,包括AR、荨麻疹等疾病的最重要的药物。     

手术治疗变应性鼻炎的研究进展

变态反应性鼻炎(allergic rhinitis,AR)简称变应性鼻炎,是指特应性个体接触致敏原后由IgE介导的介质(主要是组胺)释放,并有多种免疫活性细胞和细胞因子参与的鼻黏膜慢性炎症反应性疾病.目前对AR的治疗主要是患者教育、避免接触过敏原、药物治疗和免疫治疗等[1],另外还有如手术治疗、物理治疗、中药和针灸等.鼻用糖皮质激素可减少或控制所有或绝大多数变应性炎症介质在鼻黏膜局部的损伤作用,故被认为是防治AR的最有效的药物之一.但是,对于不宜采用该治疗的患者,变应原皮下注射和舌下含服被认为是治疗AR的、值得肯定的长期特异性免疫治疗方法,但日前对所采用变应原的最佳剂量和其长期疗效仍有待进一步研究.     

浅谈伴有变应性鼻炎的慢性鼻窦炎的治疗

慢性鼻窦炎和变应性鼻炎是两种常见的慢性上呼吸道疾病,存在着某些内在联系以及类似炎症机制。有必要完善慢性鼻窦炎、鼻息肉患者的术前变态反应检查以及治疗:包括避免过敏原(环境和食物)、免疫治疗、鼻腔冲洗、鼻用糖皮质激素、针对鼻窦病原体的抗菌药物、抗变态反应(抗组胺药、白三烯受体拮抗剂等)和抗胃食管反流。此外,维生素D诱导细胞分化、参加免疫调节和调节内分泌系统也在慢性鼻窦炎和变应性鼻炎的炎症过程中发挥重要作用。     

Treatment of acute rhinitis in neonates and infants

The authors review current views on the treatment of acute rhinitis (AR) in infants and present their experience in AR treatment of 30 infants aged from 3 days to 1 year. Combined treatment with Physiomer baby quickly eradicated inflammation. The drug eliminates crusts and nasal discharge allowing application of other medication on a clear surface of nasal mucosa. As a result, medication becomes more affective and accelerates recovery. A convenient tip is well adapted for the nostrils. Administration of medicine by spray provides optimal lavage of the nasal cavity.     

非变应性鼻炎临床特点及鼻内糖皮质激素联合抗组胺药物治疗效果分析

目的 探讨非变应性鼻炎(non-allergic rhinitis,NAR)患者年龄、性别、诱因等方面的临床特点以及鼻内糖皮质激素和抗组胺药物联合应用治疗NAR的临床效果.方法 对2009年1-8月100例首诊为NAR的连续病例的年龄、性别、诱发因素等进行分析.联合应用鼻内糖皮质激素和抗组胺药物治疗8周,分别记录治疗前后各种鼻部症状的视觉模拟量表(visual analogue scale,VAS)评分,评估治疗效果.采用SPSS 17.0软件对数据进行统计学分析.结果 100例NAR患者中93例为成人,其发病高峰年龄为30～39岁;其中男45例,女55例,男女性别比例为1:1.2;NAR患者临床症状以喷嚏(96例次)、鼻涕(88例次)、鼻塞(72例次)、鼻痒(69例次)等鼻部症状为主,同时存在眼痒(49例次)、流泪(32例次)、充血(22例次)、肿胀(13例次)等眼部症状及咳嗽(21例次)、憋气(19例次)、胸部压迫感(13例次)、喘息(10例次)等下呼吸道症状.79例(79.0%)患者可以明确指出至少一种诱因,其中气温变化(54例次)、灰尘(28例次)、刺激性气味(21例次)是主要诱因.47例患者完成鼻内精皮质激素和抗组胺药物联合治疗,其中38例(80.9%)患者治疗8周后除喘息外所有症状都明显缓解(P<0.05),但1年后当诱发因素出现时36例患者复发,需再次治疗;9例(19.1%)患者认为治疗无效.结论 NAR临床特点为:成人为主要发病人群,女性略多,但性别因素对NAR发病影响不大;喷嚏、鼻涕为主要临床症状;多存在明确诱闪.鼻内糖皮质激素和抗组胺药物联合应用能够有效控制大部分患者的临床症状.

Abstract：

Objective To investigate the basic clinical features of non-allergic rhinitis (NAR) in age, sex, incentives, and the effect of treatment with combined intranasal steroids and antihistamines. Methods One hundred consecutive NAR patients were included in this study and the age, gender, predisposing factors and clinical symptoms were analyzed. Combined intranasal steroids and antihistamines used for 8 weeks, the symptoms were recorded before and after treatment with visual analogue scale( VAS) score as the assessment of treatment effects. SPSS 17.0 software was used to analyze the data. Results Ninty-three NAR patients were adults, and the sex ratio was 1 : 1.2( male: female) , and the peak age incidence was between 30 - 39 years old. The main nasal symptoms were sneezing (96 cases) , rhinorrhea (88 cases) , nasal blockage (72 cases) and nasal itching (69 cases). The symptoms of eye and respiratory tract were always accompanied as eye itching (49 cases) , tears ( 32 cases) , congestion ( 22 cases) , swelling ( 13 cases) , cough (21 cases) , suffocation ( 19 cases) , chest compression ( 13 cases) , wheezing ( 10 cases) ; Seventy-nine(79. 0% ) patients could indicate at least one kind of incentives, the temperature change (54 cases) , dust (28 cases) , irritating odor (21 cases) was the main incentive of NAR. Forty-seven patients completed the combined treatment of intranasal steroids and antihistamines, 38 (80.9%) patients were satisfied with the result with all symptoms relieved except wheezing ( P < 0. 05 ) , but36 patients had the NAR returned when they were exposed with the predisposing factors in the coming year; the remaining 9 (19. 1 % ) patients failed the treatment. Conclusions The clinical features of NAR were as follows: adult constituted the main patient population, women were slightly more than man but with no difference between genders; sneezing and nasal discharge were the main clinical symptoms, always more than 1 incentives. The combination of intranasal steroids and antihistamines could control the most of clinical symptoms.     

Expression of uteroglobin in a murine model of allergic rhinitis

CONCLUSION: We observed for the first time the expression of Uteroglobin (UGB) in the nasal mucosa of mice. The results of our study suggest that UGB may play an important role in the regulation of inflammation in allergic rhinitis (AR) as well as in the lower airway allergic inflammations. OBJECTIVES: Uteroglobin is a protein secreted by epithelial lining of organs communicating with the external environment. Reports of its immunomodulatory effects in allergic disease have been made, but the true physiological role still remains to be elucidated. In this study we tried to observe the expression of UGB in the nasal mucosa of mice and determine its role in AR. MATERIALS AND METHODS: Thirty BALB-c mice at 3 weeks of age (10 mice/group) were sensitized systemically by intraperitoneal ovalbumin injection and locally by ovalbumin inhalation. Control group were sensitized with PBS. Treatment group had intraperitoneal dexamethasone injection 1 hour before the initial sensitization while control and AR group were injected with PBS. Symptom scores, eosinophil counts, immunohistochemical staining as well as UGB mRNA expression in the nasal mucosa and lung tissue were analyzed. RESULTS: The symptom scores and eosinophil counts between control and treatment group was significantly different from the AR group (P<0.01). On immunohistochemical staining, UGB was localized in the epithelium and submucosal gland of the nasal mucosa as well as in the epithelium of respiratory bronchioles. UGB mRNA expression of the nasal mucosa and lung tissue was decreased in the AR group compared to the control group (P=0.022). In the treatment group UGB expression was increased compared to the AR group (P=0.016). The results of IHC and mRNA expression in the lung tissue correlated with the results in the nasal mucosa.     

Oral second generation antihistamines in allergic rhinitis

BACKGROUND: Histamine is a key mediator of the allergic immediate reaction. Antihistamines belong to the most frequently used treatment modalities in allergic rhinitis. METHODS: The National Libraray of Medicine was searched for current data of the effects of histamine and antihistamines in allergic rhinitis. RESULTS: Histamine acts on 4 different histamine receptors. Activation of H1-receptors on nasal trigeminal nerve fibers transmits nasal itch and sneezing. Nasal hypersecretion is mainly mediated by an trigeminal-parasympathetic reflex. Activation of H1-receptors results in contraction of nasal endothelial cells with consecutive plasma extravasation and edema formation. Histamine also activates H2-receptors on smooth muscle cells surrounding nasal capacitance vessels. They transmit muscle relaxation, increased blood content and an enlarged volume of nasal mucosa. Via peripheral H3-receptors, histamine modulates neurogenic inflammation and via H4-receptors functions of immune cells. Oral second generation antihistamines inhibit histamine dependent activation of nasal H1-receptors. They mainly reduce nasal itch, sneezing, and hypersecretion. In addition, allergy related activity impairment is reduced resulting in improved physical and mental performance. Second generation antihistamines reduce proinflammatory effects mediated by H1-receptors, however, drug concentrations necessary for mast cell stabilization as observed in vitro are not reached in vivo. Oral second generation antihistamines are readily absorbed and reduce allergy symptoms for approximately 24 hours, allowing convenient once daily medication. Modern antihistamines are generally safe; tachyphylaxis, tolerance or rebound has not been observed. CONCLUSION: Due to their minimal adverse effects and efficient symptom reduction oral second generation antihistamines are particularly useful for the treatment of less severe intermittent forms of nasal allergy.     

Eotaxin基因和趋化因子受体3在变应性鼻炎大鼠模型鼻腔黏膜和骨髓中的表达及意义

目的：探讨Eotaxin（嗜酸粒细胞趋化因子）基因和趋化因子受体3（CCR3）在变应性鼻炎（AR）大鼠模型鼻腔黏膜和骨髓中的表达及其意义。方法：采用6～8周龄雄性SD大鼠20只,随机分成实验组（AR组）和对照组,每组10只,以卵清蛋白致敏激发制成AR模型,瑞特染色计数骨髓涂片和外周血涂片中白细胞比例,免疫组织化学技术检测骨髓中CCR3的表达;制备大鼠鼻腔黏膜组织病理标本,苏木精-伊红染色,原位分子杂交方法检测鼻腔黏膜中Eotaxin mRNA的表达,免疫组织化学技术检测Eotaxin在鼻腔黏膜中的表达。结果：AR组骨髓涂片中嗜酸粒细胞比例显著高于对照组（P〈0．01）,AR组外周血涂片中嗜酸粒细胞比例显著高于对照组（P〈0．01）;与对照组比较,AR组大鼠鼻腔黏膜中Eotaxin阳性细胞数与EotaxinmRNA表达明显增强（P〈0．01）,且二者呈正相关性（r=0．804,P〈0．01）。AR组Eotaxin的表达与鼻腔黏膜嗜酸粒细胞的数量呈显著正相关（r=0．795,P〈0．01）。AR组骨髓涂片中CCR3阳性细胞比例显著高于对照组（P〈0．01）,AR组骨髓涂片中CCR3阳性细胞比例和外周血嗜酸粒细胞比例呈显著正相关（r=0．736,P〈0．05）。结论：AR组中Eotaxin和CCR3表达增强,为嗜酸粒细胞从骨髓快速募集到鼻腔黏膜提供了可能。     

变应性鼻炎的长期抗炎治疗

已经证实许多没有症状的变应性鼻炎(AR)患者存在亚临床的炎症状态,接触阈值以下的变应原剂量能够引起鼻黏膜炎性细胞的浸润,包括细胞黏附分子、鼻腔和结膜嗜酸性粒细胞以及其他炎性标记物的表达显著增加,这些都不会导致明显的过敏症状。虽然治疗AR通常以缓解症状为主,减轻无症状时期的炎性反应可能会对AR发病、进展以及严重程度有积极的影响。因此制定治疗方案时应该充分考虑到对于症状缓解后仍存在的潜在炎性反应。目前主要有三类治疗AR的药物,包括抗组胺药、抗白三烯药和鼻内糖皮质激素,鼻内糖皮质激素对AR患者持续炎症的长期抑制可能是最合理的治疗选择。     

白细胞介素-12在变应性鼻炎鼻粘膜中的表达

目的 :探讨白细胞介素 12 (IL 12 )在变应性鼻炎鼻粘膜中的表达。方法 :以卵清蛋白为变应原建立豚鼠变应性鼻炎模型 (模型组 )。取该模型和健康豚鼠鼻粘膜行常规HE染色 (对照组 ) ,并采用逆转录 聚合酶链反应 (RT PCR)检测方法 ,对两组动物鼻粘膜组织中IL 12mRNA表达水平进行相对定量比较。结果 :IL 12mR NA在两组鼻粘膜中均有表达 ,模型组的表达水平为 0 .6 6 7± 0 .10 4显著低于正常对照组 0 .84 7± 0 .0 71(P <0 .0 1)。结论 :在变应性鼻炎鼻粘膜组织中IL 12的表达下降 ,提示应用IL 12替代疗法治疗变应性鼻炎的可能性。     

Wirkmechanismen nasaler Glukokortikosteroide in der Therapie der allergischen Rhinitis

Allergic rhinitis (AR) is the single most common allergic disease and one of the most common chronic diseases. It affects approximately 25-30% of the population, and can substantially worsen patients' medical conditions, reduce quality of life, and contribute to absenteeism from work or school. It is also responsible for substantial direct and indirect economic burdens on the health care system. The medical management of allergic rhinitis includes several available pharmacotherapies, such as α-sympathomimetics, anticholinergic drugs, natural saline or other nasal rinses, mast cell-stabilizing agents, topical and systemic antihistamines, topical and systemic glucocorticosteroids, leukotriene-receptor antagonists and the new monoclonal antibodies following a stepwise approach. Allergen-specific immunotherapy is the only treatment option that interferes with the natural course of the disease and, besides allergen elimination, is thought to be the only causative treatment option. Nasal glucocorticosteroids (nGCS) are thought to be the most effective treatment choice for controlling the symptoms of AR. Double-blind, randomized clinical trials have demonstrated greater efficacy of nGCSs versus placebo, antihistamines or montelukast for relief of all nasal symptoms, especially congestion. Therefore, especially in the management of AR-related nasal inflammation and congestion, nGCSs are considered the most appropriate treatment. Patients should be informed that symptom improvement can be expected after 2-4 days for intermittent rhinitis and after up to 2-3 weeks for persistent rhinitis. The medication has to be taken regularly and not as "on-demand" treatment. Adherence to treatment also affects outcomes, and this may be influenced by patient preferences for the sensory attributes of an individual drug and the awareness of possible side effects. More recently, safety studies have shown that the newer nGCS agents have improved safety profiles compared with older nGCS agents. The newer nGCS drugs have been found to have minimal adverse effects on growth and hypothalamic-pituitary-adrenal-axis function in children. This review will discuss the pathophysiology of allergic inflammation in the nasal mucosa and the mechanism of action of nGCSs; also the efficacy and safety of nGCSs will be discussed by focusing on clinical evidence.