硝酸铈对豚鼠变应性鼻炎鼻黏膜的影响

目的探讨1%硝酸铈溶液对豚鼠变应性鼻炎鼻黏膜的影响。方法健康豚鼠39只随机分成正常对照组,变应性鼻炎组：用2,4-二异氰酸甲苯酯（2,4-Toluene-Dissocya-nate,TDI）作致敏原,经鼻腔滴入建立变应性鼻炎模型。治疗期间变应性鼻炎组（n=30）动物随机分成3组：阳性对照组（n=10）、药物治疗对照组（n=10）、硝酸铈治疗组（n=10）,正常对照组（n=9）设为阴性对照组,治疗15d。观察症状体征、鼻分泌物涂片、鼻黏膜组胺含量和光镜和电镜下鼻黏膜组织形态学的变化。结果阳性对照组出现鼻痒、喷嚏、流清涕,鼻分泌物嗜酸性粒细胞增多,鼻黏膜组胺含量增多,嗜酸性粒细胞浸润,鼻黏膜细胞超微结构改变。与阳性对照组相比,硝酸铈治疗组上述变化明显减轻。结论 1%硝酸铈溶液能有效控制豚鼠变应性鼻炎的症状体征,使鼻黏膜嗜酸性粒细胞减少、组胺含量减低。     

布地奈德对变应性鼻炎豚鼠鼻粘膜嗜酸性粒细胞及组胺的影响

目的：制备变应性鼻炎动物模型,评价布地奈德对变应性鼻炎嗜酸性粒细胞和组胺的影响.方法：将豚鼠随机分成自然对照组、变应性鼻炎组和布地奈德治疗组,采用甲苯-2,4-二异氰酸酯对豚鼠鼻腔局部致敏激发制备变应性鼻炎模型,通过观察动物临床症状、鼻粘膜病理切片和鼻粘膜组织中组胺含量等指标来评价药物的药效.结果：变应性鼻炎组鼻粘膜组织中嗜酸细胞浸润和组胺含量均显著高于自然对照组（P＜0.01或P＜0.05）;经治疗后,动物的嗜酸细胞浸润和组织中组胺含量均明显地降低（P＜0.01）.在临床症状指标上,变应性鼻炎组和药物治疗组评分均明显高于自然对照组（P＜0.01）,但变应性鼻炎组和药物治疗组间无显著差异（P＞0.05）.结论：布地奈德能有效地降低变应性鼻炎豚鼠鼻粘膜组织中嗜酸细胞浸润和组胺的含量,但未能改善动物的鼻部临床症状,这可能与造模的方法有关.     

鼻炎通窍喷雾剂对变应性鼻炎豚鼠血清IL-4含量和鼻黏膜Bax蛋白表达的影响

目的:通过研究鼻炎通窍喷雾剂对变应性鼻炎(Allergic rhinitis,AR)模型豚鼠血清中白细胞介素4(Interleukin-4,IL-4)含量和鼻黏膜组织中Bax蛋白表达的影响,探讨鼻炎通窍喷雾剂治疗变应性鼻炎的作用机制。方法:用10%甲苯-2,4二异氰酸酯(10%toluene-2,4-diisocyanate,TDI)橄榄油溶液建立豚鼠变应性鼻炎模型;用酶联免疫吸附法(ELISA)定量测定各组豚鼠血清中IL-4的含量,免疫组化法测定鼻黏膜组织中Bax蛋白的表达。结果:实验组豚鼠血清的IL-4表达水平显著低于模型对照组(p0.01);实验组豚鼠鼻黏膜中Bax蛋白的表达水平显著高于模型对照组(P0.01)。结论:鼻炎通窍喷雾剂对变应性鼻炎的作用机制与调节免疫功能、促进炎细胞凋亡有关。     

复方苍耳子滴鼻剂对豚鼠变应性鼻炎的影响

目的观察复方苍耳子滴鼻剂对变应性鼻炎模型豚鼠症状的变化和血清组胺含量的影响。方法以甲苯-2,4-二异氰酸甲苯酯(TDI)作为致敏因子建立豚鼠鼻黏膜变态反应模型,以模型组、阳性药物组与空白组为对照,测定各组豚鼠鼻黏膜内组胺的含量及形态组织学的改变。结果 ①鼻部症状的改善情况:复方苍耳子滴鼻剂高、低剂量组药前总评分与药后总评分比较差异有统计学意义(P<0.05),能显著性改善慢性鼻炎模型动物的整体症状;②对血清组胺含量的影响:复方苍耳子滴鼻剂高、低剂量组血清组胺含量均显著低于模型组(P<0.05或0.01),能显著降低慢性鼻炎模型动物的血清组胺含量;③形态组织学的改变:复方苍耳子滴鼻剂高、低剂量对鼻黏膜上皮化生、腺体增生、血管增生或扩张及炎性细胞等方面均能显著改善慢性鼻炎模型动物的形态组织学。结论复方苍耳子滴鼻剂对豚鼠实验性变态反应性鼻炎有显著的改善作用。     

消风宣窍汤对变应性鼻炎豚鼠模型NGF和IL-5表达的影响及其相关性

目的探讨消风宣窍汤治疗变应性鼻炎（AR）的作用机制。方法将60只Hartley豚鼠随机分为正常组,模型组,消风宣窍汤高、中、低剂量组,氯雷他定组。卵蛋白（OVA）致敏成功建立变应性鼻炎豚鼠模型。药物干预后,ELISA法检测各组豚鼠血清神经生长因子（NGF）和白细胞介素-5（IL-5）的水平。结果OVA致敏后,模型组豚鼠血清NGF,IL-5含量显著高于正常组（P〈0．01）。与模型组比较,用药组豚鼠血清NGF和IL-5含量下降（P〈0．05）,其中消风宣窍汤高、中剂量下调NGF,IL-5作用更显著（P〈0．01）,消风宣窍汤低剂量亦能显著下调IL-5（P〈0．01）,且NGF和IL-5有正相相关关系（r=0．863,P〈0．01）。结论消风宣窍汤治疗AR的作用机制可能是：1）通过降低NGF含量,减少神经肽的产生,直接减少鼻黏膜的神经刺激,进而减轻鼻部症状;2）通过降低NGF含量,调整Th1／Th2免疫失衡,下调Th2细胞因子IL-15的表达,阻断IL-5对EOS的活化作用,减轻鼻黏膜病理改变,进而减轻鼻部症状,达到治疗效果。     

不同致敏原诱发过敏性鼻炎模型的比较

目的：不同致敏原诱发豚鼠过敏性鼻炎模型的比较。方法：分别以卵蛋白（OVA）、2,4-二异氰酸甲苯酯（TDI）和互隔交链孢霉作为致敏原诱发豚鼠制备过敏性鼻炎模型,以行为学观察、血清生化水平和组织学观察,考察不同模型组与人类过敏性鼻炎的符合度。结果：OVA组与空白组比较,打喷嚏次数、抓鼻次数、血清透明质酸（HA）及IgE差异有统计学意义（P〈0．001或0．01）。结论：OVA诱发过敏性鼻炎模型既在症状上符合过敏性鼻炎的典型症状,又在病理改变上与过敏性鼻炎相符合。     

Let-7e-5p调控Fas/FasL影响小鼠变应性鼻炎发病的机制研究

目的 探讨let-7e-5p对小鼠变应性鼻炎的影响及机制。方法 将18只BALB/c小鼠按随机数字表法均分为对照（Control）组、变应性鼻炎（AR）组、let-7e-5p激动剂阴性对照（AR+agomir-NC）组、let-7e-5p激动剂（AR+agomir）组、let-7e-5p抑制剂阴性对照（AR+antagomir-NC）组和let-7e-5p抑制剂（AR+antagomir）组。除Control组外，其余组应用卵白蛋白（OVA）致敏建立AR模型，AR+agomir组和AR+antagomir组同时给予let-7e-5p agomir或let-7e-5p antagomir进行干预，末次激发致敏后对小鼠变应性鼻炎进行评分，HE染色观察鼻黏膜组织，统计嗜酸性粒细胞数量，real-time PCR检测let-7e-5p、Fas、FasL m RNA表达，Western blot检测Fas、FasL蛋白表达，酶联免疫吸附试验检测血清免疫球蛋白E(IgE)、特异性IgE(sIgE)、干扰素γ(IFN-γ)、白细胞介素（IL）-12、IL-4、IL-13水平，双荧光素酶实验分析let...     

盐酸左旋咪唑治疗豚鼠变应性鼻炎的药效学研究

目的:考察盐酸左旋咪唑经鼻腔给药治疗豚鼠变应性鼻炎的疗效,为治疗变应性鼻炎寻找新的药物。方法:建立豚鼠变应性鼻炎的模型;以雷诺考特为阳性对照药,以生理盐水为阴性对照药,经鼻腔给予盐酸左旋咪唑后,观察变应性鼻炎豚鼠的鼻分泌物、抓痒和喷嚏情况,鼻粘膜的组织病理变化、嗜酸性粒细胞浸润和组胺含量的变化情况。结果:布地奈德组和左旋咪唑各剂量组经治疗均未能有效地改善豚鼠AR的临床症状。左旋咪唑低中高三个剂量组治疗后均能极显著抑制嗜酸细胞,与布地奈德组无显著性差别。中剂量组和高剂量组的左旋咪唑治疗后能显著性地降低鼻粘膜中组胺的含量,且与布地奈德组无显著性差别。结论:盐酸左旋咪唑经鼻腔给药对豚鼠变应性鼻炎具有一定的疗效,有可能成为新的变应性鼻炎的治疗药。     

白介素-1受体拮抗剂对豚鼠变应性鼻炎的治疗作用

目的：明确白介素-1受体拮抗剂对变应性鼻炎的治疗作用。方法：采用甲苯-2,4-二异氰酸酯（TDI toluene-2,4-diisocyanate)致敏豚鼠,制作变应性鼻炎模型,观察给予白介素-1受体拮抗剂（IL-1ra）处理前后症状和体征的变化,用组织病理学方法观察鼻粘膜的改变,测量鼻粘膜中组胺、血中IgE的含量。结果：用IL-1ra治疗后,变应性鼻炎症状和体征明显改善,HE染色显示,鼻粘膜水肿及炎性细胞浸润,随IL-1ra浓度的提高而改善,鼻粘膜中组胺、血中IgE的含量下降,随白介素-1拮抗剂浓度升高而下降。特别是高剂量组,各指标好于其它各治疗组,阳性对照组也有鼻粘膜水肿,及炎性细胞浸润。结论：局部使用IL-1ra拮抗剂能治疗变应性鼻炎。     

miR-107在变应性鼻炎小鼠鼻黏膜中的表达及作用

目的 探讨miR-107在变应性鼻炎(AR)小鼠鼻黏膜中的表达及其作用机制。方法 采用卵清蛋白(OVA)腹腔注射及滴鼻建立AR模型，实验分为Sham组(腹腔注射0.9%氯化钠溶液、滴鼻处理)、AR组、AR+miR-NC组(OVA致敏后用带有miR-NC的腺病毒注射入小鼠腹腔)、AR+miR-107组(OVA致敏后用带有miR-107过表达载体的腺病毒注射入小鼠腹腔),每组10只。qRT-PCR法检测外周血、鼻黏膜组织中miR-107表达量；采用视觉模拟评分量表(VAS)评估鼻部症状；试剂盒检测血清OVA特异性免疫球蛋白E(IgE)水平；ELISA法检测IL-4、IL-5、IFN-γ水平；Western blot检测NLRP3炎性小体相关蛋白(NLPR3、ASC)表达量。结果 与Sham组比较，AR组外周血、鼻黏膜组织中miR-107表达水平、IFN-γ水平降低(P<0.05),鼻部症状评分、NLPR3、ASC蛋白水平升高(P<0.05),血清OVA特异性IgE、IL-4、IL-5水平升高(P<0.05);与AR组、AR+miR-NC组比较，AR+miR-107组外周血...     

A comprehensive model of allergic rhinitis in guinea pigs

INTRODUCTION: The economic and social impact of allergic rhinitis is substantial. The effectiveness of currently available medications is limited and therefore investigations for more effective drugs is essential. This study was intended to establish a model of allergic rhinitis in guinea pigs that can be utilized for further investigation of new drugs. METHODS: Male Dunkin Hartley guinea pigs were sensitized intranasally to, and challenged with, ovalbumin. Sneezing (SN) and nose rubbing (NR) response to allergen challenge were observed on day 21 post-initiation of sensitization in conscious guinea pigs. Nasal blockade (NB), leukocyte infiltration, and lung inflation pressure (LIP) were assessed in the same guinea pigs 23-28 days post-initiation of sensitization. A ventilator/flow method was used to measure NB and LIP. Leukocyte infiltration into nasal lavage fluid 60 min after challenge in the same animals was recorded as total and differential cell counts. RESULTS: Sensitized guinea pigs produced acute allergic responses after allergen challenge. This was characterized by increases in SN, NR, NB, and eosinophil infiltration. In addition, intranasal allergen challenge did not change lung inflation pressure. DISCUSSION: Allergen-induced rhinitis in guinea pigs resembles that in humans. The model reported in this study can be used to reflect the effectiveness of drugs currently used to treat allergic rhinitis and to investigate new potential drugs for the treatment of allergic rhinitis.     

鼻敏片对寒证变应性鼻炎豚鼠辅助性T细胞17/调节性T细胞平衡的影响

目的:探讨鼻敏片对寒证变应性鼻炎(allergic rhinitis,AR)豚鼠辅助性T细胞17(Th17)/调节性T细胞(Treg)表达水平的影响及其作用机制.方法:将40只雄性豚鼠随机分为空白组、模型组、鼻敏片组和氯雷他定片组,以复方凉药+卵清蛋白致敏法建立寒证AR模型后给予相应的药物干预,治疗15 d后,取血清和...     

Comparison of cedar pollen-induced allergic rhinitis in passively and actively sensitized guinea pigs

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.     

碧云喷雾剂对豚鼠变应性鼻炎的干预作用

目的 研究碧云喷雾剂对2,4-甲苯二异氰酸酯(TDI)致豚鼠变应性鼻炎的治疗作用. 方法 以TDI为致敏原,建立豚鼠变应性鼻炎模型,将实验动物随机分为正常对照组、模型对照组、碧云喷雾剂组、酮替芬组. 正常对照组和模型对照组给予相应容量0.9%氯化钠溶液,碧云喷雾剂组给予碧云喷雾剂96 mg.kg^-1(相当于临床等效剂量的2倍),酮替芬组给予酮替芬0.07 mg.kg^-1. 连续给药7 d. 观察各组鼻部过敏症状并评分,对鼻黏膜组织做病检,并对嗜酸性粒细胞(EOS)、肥大细胞(MC)计数. 结果正常对照组、模型对照组、碧云喷雾剂组、酮替芬组鼻部过敏症状评分分别由治疗前(1.17±0.63),(7.05±1.24),(7.56±1.05),(7.69±0.96)分,降为(1.11±0.54),(7.33±0.67),(4.92±0.96),(5.14±0.77)分,碧云喷雾剂明显降低豚鼠鼻部过敏症状评分(P<0.01). 鼻黏膜组织病理变化得到明显改善,正常对照组、模型对照组、碧云喷雾剂组、酮替芬组EOS分别为(1.68±0.85),(9.13±1.68),(4.51±2.25),(3.59±1.77)个;MC 分别为(2.23±1.26),(21.03±5.03),(14.05±6.88),(13.14±5.41)个,脱颗粒MC 分别为(1.32±1.03),(13.64±5.47),(8.49±2.37),(6.06±2.55)个,碧云喷雾剂下调EOS、MC作用明显(P<0.01). 结论 碧云喷雾剂对豚鼠TDI致变应性鼻炎有一定的治疗作用.     

苯环喹溴铵对大鼠变应性鼻炎的治疗作用

目的探讨苯环喹溴铵对大鼠变应性鼻炎的治疗作用及机制。方法以卵清白蛋白(Ova)和Al (OH)_3建立大鼠变应性鼻炎模型。将60只大鼠随机分为模型组,苯环喹溴铵大、中、小剂量组,倍氯米松组和溶媒对照组,每组10只大鼠。各组动物经鼻给予相应药物2 wk后,观察各动物的症状和鼻黏膜组织形态学的状况,对各动物单侧鼻分泌物进行称重,并检测血清和鼻黏膜中Ova特异性IgE。结果模型组大鼠症状评分、鼻分泌物重量、血清和鼻分泌物中Ova特异性IgE水平及鼻黏膜病理学评分均高于溶媒对照组(P<0.01)。与模型组相比,苯环喹溴铵各剂量组大鼠的鼻炎症状均得到明显改善(P<0.01);大、中剂量组大鼠鼻黏膜的组织形态改变明显减轻(P<0.01);大剂量组大鼠血清和鼻黏膜中的Ova特异性IgE水平以及鼻分泌物量均明显降低(P<0.01)。结论经鼻给予苯环喹溴铵,对于大鼠变应性鼻炎有明显的治疗作用,其作用机制之一可能是通过降低Ova特异性IgE来实现的。     

Evaluation of nasal barrier dysfunction at acute- and late-phase reactions in a guinea pig model of allergic rhinitis

Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs.