基质金属蛋白酶9和肿瘤坏死因子α表达与大鼠上下呼吸道炎性反应一致性研究

目的 通过建立变应性鼻炎(allergic rhinitis,AR)和支气管哮喘(简称哮喘,asthma,AS)动物模型,探讨基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)和肿瘤坏死因子α(tumor necrosis factor,TNF-α)在上下呼吸道炎性反应一致性中的作用及机制.方法 以卵清蛋白辅以氢氧化铝致敏并激发制成AR和AS大鼠模型.HE染色和甲苯胺蓝染色分别检测AR和AS大鼠模型鼻黏膜及肺组织中嗜酸粒细胞、肥大细胞的表达,免疫组化SP法检测上述组织中MMP-9和TNF-α的表达,分析嗜酸粒细胞、肥大细胞、MMP-9和TNF-α表达与上下呼吸道炎性反应的关系.采用SPSS13.0软件对数据进行统计学分析.结果 MMP-9阳性细胞数在AR组鼻黏膜和肺组织中分别为 (154.8±12.0)、(124.0±8.2)个,在AR对照组分别为(43.2±7.6)、(34.5±5.0)个,差异有统计学意义(t值分别为24.260、29.525,P值均＜0.05);MMP-9阳性细胞数在AS组鼻黏膜和肺组织中分别为(149.9±11.7)、(120.1±7.3)个,在AS对照组分别为(48.6±7.6)、(39.1±5.2)个,差异有统计学意义(t值分别为22.929、28.530,P值均＜0.05).TNF-α阳性细胞数在AR组鼻黏膜和肺组织中分别为(188.8±17.0)、(134.8±7.9)个,在AR对照组分别为(57.6±23.3)、(40.3±8.2)个,差异有统计学意义(t值分别为13.836、26.220,P值均＜0.05);TNF-α阳性细胞数在AS组鼻黏膜和肺组织中分别为(179.2±15.4)、(153.5±10.1)个,在AS对照组分别为(70.5±33.1)、(33.8±14.0)个,差异有统计学意义(t值分别为9.412、21.858,P值均＜0.05).MMP-9与TNF-α在AR组鼻黏膜及肺组织中的表达分别呈正相关(r值分别为0.893和0.700,P值分别为0.001和0.024),二者在AS组鼻黏膜或肺组织中的表达分别呈正相关(r值分别为0.692和0.644,P值分别为0.027和0.044).结论 上下呼吸道炎性反应具有一致性,MMP-9和TNF-α可能在上下呼吸道炎性反应一致性中发挥重要作用.

Abstract：

Objective To investigate the role and mechanism of matrix metalloproteinase 9(MMP-9) and tumor necrosis factor α (TNF-α) in the pathogenesis of allergic rhinitis (AR) and asthma (AS). Methods The rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin (HE) staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining ( SP method). The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data. Results The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were ( 154.8±12.0)and (124. 0 ±8.2), (43. 2 ±7.6) and (34. 5 ±5.0) in the control groups, the difference was significant (t value were 24. 260, 29. 525 respectively, all P＜0.05). The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were (149.9±11.7)and(120.1±7.3), (48.6 ± 7. 6) and (39.1±5.2)in control groups, the difference was significant (t value were 22. 929 and 28. 530respectively, all P＜0.05).The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were (188.8±17.0), and (134.8±7.9), (57.6±23.3)and(40. 3 ± 8. 2 ) in control groups, the difference was significant (t value were 13. 836 and 26. 220, all P ＜0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were (179. 2 ± 15.4 ) and ( 153. 5 ± 10. 1 ), (70. 5 ±33. 1 ) and ( 33.8 ± 14. 0) in control groups, the difference was significant ( t value were 9. 412 and 21. 858, all P ＜0. 05). There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR ( r values were 0. 893 and 0. 700 respectively, P values were 0. 001 and 0. 024, respectively ) and AS ( r values were 0. 692 and 0. 644 respectively, P values were 0. 027and 0. 044 respectively) groups. Conclusions The inflammation is similar between AR and AS. The MMP9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.     

Role and mechanism of the expression of matrix metalloproteinase 9 and tumor necrosis factor α in upper and lower respiratory tract inflammation in rats

Objective To investigate the role and mechanism of matrix metalloproteinase 9(MMP-9) and tumor necrosis factor α (TNF-α) in the pathogenesis of allergic rhinitis (AR) and asthma (AS). Methods The rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin (HE) staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining ( SP method). The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data. Results The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were ( 154.8±12.0)and (124. 0 ±8.2), (43. 2 ±7.6) and (34. 5 ±5.0) in the control groups, the difference was significant (t value were 24. 260, 29. 525 respectively, all P＜0.05). The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were (149.9±11.7)and(120.1±7.3), (48.6 ± 7. 6) and (39.1±5.2)in control groups, the difference was significant (t value were 22. 929 and 28. 530respectively, all P＜0.05).The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were (188.8±17.0), and (134.8±7.9), (57.6±23.3)and(40. 3 ± 8. 2 ) in control groups, the difference was significant (t value were 13. 836 and 26. 220, all P ＜0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were (179. 2 ± 15.4 ) and ( 153. 5 ± 10. 1 ), (70. 5 ±33. 1 ) and ( 33.8 ± 14. 0) in control groups, the difference was significant ( t value were 9. 412 and 21. 858, all P ＜0. 05). There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR ( r values were 0. 893 and 0. 700 respectively, P values were 0. 001 and 0. 024, respectively ) and AS ( r values were 0. 692 and 0. 644 respectively, P values were 0. 027and 0. 044 respectively) groups. Conclusions The inflammation is similar between AR and AS. The MMP9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.     

鼻息肉患者鼻腔淋巴系统核素显影的初步研究

目的 探讨鼻腔黏膜淋巴引流障碍在鼻息肉患者鼻黏膜中的表现.方法 应用核素显影技术对25例鼻息肉患者(试验组,又分为Malm-1、Malm-2、Malm-3级3个亚组)和需行前哨淋巴结核素检查且经鼻内镜检查鼻腔结构正常的6例甲状腺腺癌、喉癌等患者(对照组)的鼻腔黏膜特定部位进行核素注射,通过影像结果分析鼻腔黏膜淋巴引流状况.结果 试验组及对照组注射部位均未见到明显的淋巴显影及引流征象,但试验组注射点周围存在显影剂滞留现象.试验组、对照组感兴趣区(region of interest,ROI)内放射性计数比值((x)±s,以下同)分别为29.33 ±6.34、20.66 ±1.89,差异有统计学意义(t=3.275,P＜0.05).试验组中Malm-1、Malta-2、Malm-3级3个亚组ROI内放射性计数比值分别为24.40 ±3.19、29.31±3.39、39.21±3.15,3个亚组比较,差异有统计学意义(F=38.980,P＜0.05).结论 鼻息肉患者鼻黏膜淋巴引流存在功能紊乱.

Abstract：

Objective To explore the role of nasal mucosal lymphatic drainage in the pathogenesis of nasal polyps.Methods There were 25 cases in the experimental group who had nasal polyps ( which was further divided into Malm-1,Malm-2,Malm-3 level 3 subgroups)and 6 cases in the control group,including thyroid cancer and laryngeal cancer patients who had normal nasal structure.The nasal polyps in the experimental group and the middle turbinate in the control group were injected with a radionuclide and a radionuclide imaging technique was used to image the nasal mucosal lymphatics.The lymphatic drainage status of the nasal mucosa through the imaging results was analysed.Results The T/NT ratio ( radioactivity counting) of the region of interest( ROI) was 20.66 ± 1.89 in the control group and 29.33 ± 6.34 in the experimental group.The difference was significant (t =3.275 ,P ＜0.05 ) .The T/NT ratio of the ROI was 24.40 ±3.19 in the Malm-1 level group,29.31 ± 3.39 in the Malm-2 level group,39.21 ± 3.15 in the Malm-3 level group.The differences of qualitative analysis were significant ( F = 38.980,P ＜0.05 ) .The quantitative analysis showed that at the injection site,signs of lymphatic development and drainage were not found in the control group or experimental group,but the phenomenon of contrast media retention existed at the injection site in the experimental group.Conclusion Lymphatic drainage dysfunction exists in patients with nasal polyps,and it may play a role in the pathogenesis of nasal polyps.     

Expression of COX-2 and transcription factor CCAAT enhancer binding proteinβin refractory sinusitis with nasal polyps and its significance

Objective To study the expression and significance of COX-2 and C/EBP-βin refractory sinusitis with nasal polyps,and to explore the relationship between them and the recurrence of sinusitis with nasal polyps.Methods The protein expression of COX-2 and C/EBP-βin 20 cases of refractory sinusitis with nasal polyps,20 cases of sinusitis with nasal polyps and 20 cases of normal nasal mucosa were detected by western blot,and the relationship between the two was compared.Results The expression levels of COX-2 and C/EBP-βin refractory sinusitis with nasal polyps were significantly different from those in refractory sinusitis with nasal polyps(P<0.05);The expression levels of COX-2 and C/EBP-βin sinusitis tissues with nasal polyps were significantly different from those in normal nasal mucosa tissues(P<0.05);The expression levels of COX-2 and C/EBP-βin each group were significantly correlated(P<0.05).Conclusions The high expression of COX-2 and C/EBP-βmay be closely related to postoperative recurrence of sinusitis patients with nasal polyps.Both may be used as objective indicators to judge the postoperative follow-up and recurrence tendency of patients with sinusitis with nasal polyps..     

鼻中隔矫正术或联合下鼻甲骨折外移术对鼻腔模拟气流场及气道结构影响的分析

目的 探讨鼻中隔矫正术或联合下鼻甲骨折外移术对鼻腔气流场及气道结构的影响.方法 对2006-2009年诊治的6例"C"型鼻中隔偏曲患者行鼻中隔矫正术或联合下鼻甲骨折外移术,术前及术后分别行鼻CT检查,根据CT分别对手术前后鼻腔气道结构进行表面三维重建,设定边界条件并求解Navier-Stokes方程.对比分析手术前后通气量为12 L/min时气流场、气道结构变化.采用SPSS 12.0软件进行非参数秩和检验.结果 术前气道总面积、总鼻道中、下部面积宽敞侧分别为(1.61±0.18)、(0.40±0.10)、(0.40±0.14)cm2,狭窄侧分别为(1.30±0.18)、(0.33±0.05)、(0.36±0.10)cm2,双侧对比差异无统计学意义(Z值分别为1.782、1.363、0.526,P值均＞0.05);气道总流量、总鼻道中、下部流量、下鼻甲厚度宽敞侧分别为(361±68)、(131±25)、(100±28)ml,(0.93±0.10)cm,狭窄侧分别为(178±33)、(59±26)、(59±18)ml,(0.58±0.12)cm,双侧对比差异均有统计学意义(Z值分别为2.207、2.201、2.201、2.214,P值均＜0.05);双侧气流形式均紊乱.术后气道总面积宽敞侧、狭窄侧分别为(2.55±0.44)、(2.20±0.72)cm2,术后狭窄侧总鼻道中、下部面积分别为(0.58±0.13)、(0.81±0.26)cm2,术后宽敞侧下鼻甲厚度为(0.73±0.08)cm,与术前对比差异均有统计学意义(Z值分别为2.201、2.201、2.201、2.201、2.264,P值均＜0.05);双侧气流形式稳定.术后气道阻力[(0.16±0.01)kPa·L-1·s-1]较术前[(0.41±0.03)kPa·L-1·s-1]明显减小,差异有统计学意义(Z=-2.207,P=0.027).结论 鼻中隔偏曲患者术前鼻腔气道呈失代偿性改变,通气功能减退;行鼻中隔矫正术或联合下鼻甲骨折外移术后通气功能好转,但气道结构仍有继发性、自适应性改变.

Abstract：

Objective To explore the effect of septoplasty or in combination with outfracture of the inferior turbinate in patients with nasal septum deviation on the airflow field and the nasal airway structure.Methods Six patients with nasal septum deviation underwent spiral CT imaging scans before surgery and during the follow-up.The 3D finite element meshes of the nasal airway were developed from the above CT scans.Given three preconditions,the nasal airflow fields were described by the Navier-Stokes and continuity equations at the inspiratory flow rate of 12 L/ min. The whole airflow patterns were obtained and then compared with the airflow filed and airway structure changes before and after surgery.SPSS 12.0 software was used to analyze the data.Results Before surgery,area of the common airway and the middle and ventral medial regions in the concave side were (1.61 ± 0.18),(0.40 ± 0.10),(0.40 ± 0.14) cm2 respectively,and those of convex side were (1.30 ±0.18),(0.33 ±0.05),(0.36 ±0.10) cm2 respectively.The differences between both sides were of no statistical significance (Z value was 1.782,1.363,0.526 respectively,all P ＞ 0.05).Airflow of the above airways were (361 ± 68),(131 ± 25),(100 ±28) ml respectively in concave side and (178 ± 33),(59 ± 26),(59 ± 18) ml respectively in convex side, which differences were significant statistically (Z value were 2.207,2.201,2.201respectively,all P ＜ 0.05＝.The inferior turbinate in concave side [(0.93 ± 0.10) cm] was statistically (Z=2.214,P＜0.05＝ bigger than that in convex side[(0.58 ±0.12)cm] before surgery.The airflow fields were in disorder in both ill-airways.After surgery,area of the common airway was (2.55 ±0.44) cm2in concave side and (2.20 ± 0.72)cm2 in convex side respectively,and area of the middle and ventral medial regions in the convex side were (0.58 ± 0.13),(0.81 ± 0.26)em2 respectively,which differences were of significance statistically when comparing to areas before surgery (Z value were 2.201,2.201,2.201,2.201,P ＜0.05＝.The airflow passed through nasal airway orderly in both sides.But the thickness of inferior turbinate was (0.73 ±0.08)cm in concave side after surgery,which difference was significant statistically in comparison to that before surgery (Z = 2.264,P ＜ 0.05＝.Consequently,nasal resistance decreased from (0.41 ± 0.03) k Pa · L- 1 · s - 1 to (0.16 ± 0.01) kPa · L -1 · s - 1 after surgery,the difience was significantly(Z = -2.207,P = 0.027).Conclusion Septoplasty or in combination with outfracture of the inferior turbinate,followed by the self-adaptation consecutively,could improve the airway and breathing capacity of the nose.     

变应性鼻炎患病率及相关因素调查

目的 通过对变应性鼻炎(alkrgic rhinitis,AR)流行病学之大样本的调查,获得以农村为主的AR的患病率及相关患病因素.方法 2007年4月至2009年5月在河北省沧州市农村、渤海湾黄骅市沿海渔村、承德市雾灵山区、天津市区分别以行政乡、村和街道、居民小区等为单位,按行政乡、村和街道、居民小区名册通过随机多级抽样和整群抽样抽取调查对象.然后按住户自然顺序,逐一入户直接调查.同时按照自然数排序全部受调查人群,对每逢个位数0、1、5的受调查者抽取3～5 ml静脉血,由实验室专职人员做血清特异性IgE(specific IgE,sIgE)检测.采用SPSS 13.0软件对数据进行统计学分析.结果 本次流行病学调查对象共抽取5010人,其中有鼻变应性症状或体征者823例(16.4%).进行血清sIgE检测1576例,阳性402例(25.5%),其中146例合并有鼻变应性症状或体征者确诊为AR,AR的患病率为9.3%(146/1576).不同年龄、职业、特应性体质以及有无鼻部变应性症状人群之间sIgE检测阳性率差异均有统计学意义(x2值分别为7.96、9.73、16.53、8.95,P值均＜0.05).AR与支气管哮喘的发生呈正相关(回归系数β=2.544,P＜0.01).农村最常见的变应原为狗上皮、猫上皮,城市最常见的变应原为屋尘螨、粉尘螨.结论 AR的患病率无论在城市还是在农村都比较高,应受到重视.AR的发生与特应性体质、环境因素等有关.

Abstract：

Objective To obtain the prevalence and related factors in allergic rhinitis (AR) and other allergic diseases in rural area in China through epidemiological investigation with large sample and multi-faceted survey data. Methods Face to face survey was conducted in different regions( rural areas of Cangzhou, Hebei, coastal fishing village of Bohai Bay, area of Wuling Mountain, Chengde, urban areas of Tianjin) from April 2007 to May 2009. In the same time, serum specific IgE(sIgE) was detected in the digits of every 0, 1or 5 in them. SPSS 13.0 software was used to analyze the data. Results Five thousand and ten cases were investigated. There were 823 cases with the symptoms or signs of AR ( 16. 4% ). Four hundred and two cases were found to have positive serum sIgE antibody in 1576 detected cases(25.5% ).One hundred and fourty-six cases with nasal allergic symptoms or signs were diagnosed as AR. The incidence of AR was 9. 3% ( 146/1576 ). The occurrence of allergic symptoms or signs had a significant statistical difference with factors such as age, occupation, atopic constitution ( x2 value were 7. 96, 9. 73, 16. 53,8.95 respectively, all P ＜ 0. 05 ), and it was closely related to lower respiratory tract allergies ( β = 2. 544,P ＜0. 01 ). The most common allergens were dog and cat epithelium in rural areas and dust mites in city.Conclusions The incidence of AR is higher whether in urban or rural areas, it should be taken seriously as the impact on human health. The occurrence is closely related to physical characteristics and environmental factors.     

舌下粉尘螨滴剂治疗儿童支气管哮喘伴变应性鼻炎的有效性和安全性

目的 探讨舌下含服标准化粉尘螨变应原疫苗治疗儿童支气管哮喘伴变应性鼻炎的有效性和安全性.方法 采用前后自身对照,比较52例年龄4～14岁粉尘螨过敏的支气管哮喘伴变应性鼻炎患儿治疗前及免疫治疗1年、2年后的症状评分、药物评分以及不良反应发生率,评价其疗效和安全性.以SPSS 17.0软件对数据进行统计学分析.结果 治疗前患儿支气管哮喘日间、夜间的症状评分分别为(3.22±0.66)、(2.05±0.57)分,治疗后1年分别为(1.68±0.61)、(0.94±0.32)分,治疗后2年分别为(0.61±0.28)、(0.43±0.13)分,治疗后1年较治疗前明显降低,治疗后2年较治疗后1年明显降低.差异均有统计学意义(q值分别为15.25、13.78、10.29、6.07,P值均<0.01).治疗前患儿变应性鼻炎的症状评分及药物评分分别为(2.34±0.59)、(3.09±1.01)分,治疗后1年分别为(1.21±0.46)、(1.89±0.64)分,差异有统计学意义(q值分别为15.48、18.61,P值均<0.01);治疗后2年分别为(1.02±0.37)、(1.49±0.38)分,与治疗后1年相比筹异无统计学意义(q值分别为2.53、2.78,P值均>0.05).治疗过程中未发生严重不良事件,仅表现为口腔不适感.结论 标准化粉尘螨变应原疫苗舌下含服是一种治疗儿童粉尘螨支气管哮喘伴变应性鼻炎的安全有效方法.

Abstract：

Objective To study the clinical efficacy of sublingual immunotherapy using standardized dermatophagoides farinae extract for children with combined allergic rhinitis and asthma syndrome. Methods Fifty-two children, from 4 to 14 years of age, with mite-sensitive combined allergic rhinitis and asthma syndrome were treated sublingually with standardized dermatophagoides farinae extract. The clinical efficacy was evaluated by monthly follow-up visits. After treatment for 1 or 2 years using the standardized dermatophagoides farinae extract, the asthma and rhinitis symptom scores, medication scores and adverse reactions before and after treatment were evaluated. SPSS 17.0 software was used to analyze the data. Results The allergic asthma symptom scores before treatment during the day were 3. 22 ±0. 66 and at night 2.05 ±0. 57. After 1 year of treatment, the day and night scores ( 1. 68 ± 0. 61 , 0. 94 ± 0. 32) respectively, were decreased significantly (q values were 15. 25 and 13. 78 respectively, all P < 0. 01 ). After 2 years of treatment, the scores (0. 61 ± 0. 28, 0. 43 ±0. 13 ) were also decreased significantly ( q values were 10. 29 and 6. 07 respectively, all P < 0. 01 ). The allergic rhinitis symptom scores and medication scores were 2. 34 ± 0. 59 and 3. 09 ±1.01 respectively before treatment and 1.21 ± 0. 46 and 1. 89 ±0. 64 after 1 year of treatment. The differences were significant ( q values were 15. 48 and 18. 61 respectively, all P<0.01). The allergic rhinitis symptom scores and medication scores were 1.02 ±0.37 and 1.49 ± 0. 38 after 2 years of treatment. There was no significant difference between 2 years of treatment and 1 year of treatment(q values were 2.53 and 2.78 respectively, all P >0.05). There were no severe adverse events during the treatment, except for mild mouth cavity discomfort. Conclusions Suhlingual immunotherapy using standardized dermatophagoides farinae extract is safe and effective in the treatment ofchildren with combined allergic rhinitis and asthma syndrome.     

冷束缚应激对变应性鼻炎大鼠鼻黏膜中嗜酸粒细胞及白细胞介素2和6表达的影响

目的 探讨冷束缚应激对实验大鼠变应性鼻炎(allergic rhinitis,AR)模型鼻黏膜中嗜酸粒细胞及白细胞介素(interleukin,IL)2和IL-6表达的影响.方法 选健康雌性大鼠50只,以随机数学表法分为5组,每组10只:空白对照组(A组)、AR模型组(B组)、先应激后AR造模组(C组)、先AR造模后应激组(D组)、应激与AR造模同时进行组(E组).空白对照组及各实验组造模后,取大鼠鼻中隔两侧的呼吸区黏膜制备成石蜡切片后进行HE染色及IL-2、IL-6免疫组织化学染色,显微镜下利用图像分析系统,取5个视野嗜酸粒细胞、IL-2、IL-6阳性细胞计数的平均值进行分析.结果 经冷束缚应激后的C、D、E组大鼠鼻黏膜中嗜酸粒细胞计数(x-±s,以下同)高于B组(14.1±3.2)及A组(2.3±1.4),差异有统计学意义(F值分别为7.06和8.54,P值分别＜0.05和0.01);C、D、E组IL-6阳性细胞数高于B组(15.3±4.8)及A组(4.9±2.4),差异有统计学意义(F值分别为7.14和8.20,P值分别＜0.05和0.01);C、D、E组IL-2阳性细胞数低于B组(14.4±3.5)及A组(15.4±4.1),差异有统计学意义(F值分别为7.27和7.32,P值分别＜0.05和0.01).C、D、E三组间,嗜酸粒细胞计数、IL-2和IL-6阳性细胞数3项指标差异均无统计学意义(F值分别为2.90、3.12、3.20,P值均＞0.05).结论 鼻黏膜组织中嗜酸粒细胞及IL-6在空白对照组几乎不表达,在AR组中度表达,在经过冷束缚应激的AR大鼠中高度表达,且冷束缚应激与AR造模的先后时间顺序对嗜酸粒细胞及IL-6的表达没有影响.冷束缚应激的AR各组大鼠鼻黏膜组织中IL-2表达明显减少.     

白介素12基因治疗对变应性鼻炎小鼠嗜酸粒细胞及白介素5的影响

目的 探讨经鼻局部给予脂质体包裹的白细胞介素(interleukin,IL)12基因治疗对变应性鼻炎(allergic rhinitis,AR)小鼠模型鼻黏膜、外周血和骨髓中嗜酸粒细胞(eosinophils,EOS)的调节作用及相关因子IL-5的影响.方法 采用6～8周雄性BALB/C小鼠,随机分成AR组、基因治疗组和健康对照组,每组12只.卵清蛋白(ovalbumin,OVA)致敏激发建立AR模型,治疗组激发前经鼻给予脂质体包裹的pGEG.m IL-12,对照组用生理盐水代替.三组分别用HE染色计数鼻黏膜中EOS的数量,用瑞氏染色计数骨髓涂片中EOS数,以流式细胞仪检测外周血中的EOS数;免疫组化染色检测鼻黏膜和骨髓中IL-5的表达,以ELISA方法检测血清中的IL-5含量.采用单因素方差分析进行统计学处理.结果 三组小鼠中,各检测指标在各组之间的差异均有统计学意义(P值均<0.01).两两比较发现,基因治疗组鼻黏膜EOS数为(4.6±2.6)个/高倍镜视野,低于AR组的(26.5±9.8)个/高倍镜视野,差异有统计学意义(P<0.05);IL-5阳性细胞数[(3.0±1.3)个/高倍镜视野]也低于AR组[(17.6±6.4)个/高倍镜视野],差异有统计学意义(P<0.05);骨髓涂片中EOS(0.040±0.029)低于AR组(0.086±0.014),差异有统计学意义(P<0.05),IL-5阳性细胞数(0.035±0.012)也低于AR组(0.083±0.025),差异有统计学意义(P<0.05).基因治疗组外周血中EOS(0.124±0.031)低于AR组(0.184±0.079),差异有统计学意义(P<0.05),IL-5[(29.51±6.68)pg/ml]也低于AR组[(56.58±16.80)pg/ml],差异有统计学意义(P<0.05).结论 经鼻局部给予脂质体包裹的pGEG.m IL-12能够通过降低骨髓、外周血和鼻黏膜中IL-5的表达,进而减少骨髓、外周血和鼻黏膜中EOS的数量,IL-12基因治疗可能为呼吸道变应性炎症开辟一种新的治疗途径.     

吸入二氧化硫对小鼠变应性鼻炎的影响

目的 观察二氧化硫(sulphur dioxide,SO2)对小鼠变应性鼻炎(AR)的影响,探讨SO2对鼻黏膜的毒性作用机理.方法 纯系雄性昆明小鼠50只,随机分为对照组、AR组和3个SO2吸入组(在AR基础七吸入不同剂量的SO2),共5组,每组10只.收集各组小鼠鼻腔灌洗液和外周血,采用间接酶联免疫吸附试验法(ELISA)检测血清和鼻腔灌洗液中自细胞介素5(IL-5)和白细胞介素13(IL-13)的水平;常规HE染色观察鼻窦黏膜中嗜酸粒细胞的浸润情况;免疫组化染色分析鼻窦黏膜中表面活性蛋白D(surfactant protein D,SP-D)的表达.结果 随着吸入SO2剂量的增加,血清和鼻腔灌洗液中IL-5、IL-13的水平增高,鼻窦黏膜中嗜酸粒细胞的浸润增多,且均呈正相关(r值分别为0.894、0.874、0.894、0.891及0.870,P值均＜0.01).56 mg/m3和112 mg/m3 SO2吸入组鼻窦黏膜中SP-D的表达随着吸入SO2浓度的增高而增强,而168 mg/m3 SO2吸入组中SP-D的表达反而降低(P＜0.001).结论 鼻腔吸入的SO2可以促进Th2细胞因子表达,增加鼻黏膜嗜酸粒细胞浸润,在一定程度上加重AR病变.     

内源性一氧化碳对变应性鼻炎豚鼠诱导型一氧化氮合酶表达的影响

目的 制备豚鼠变应性鼻炎(allergic rhinitis,AR)动物模型,研究在AR豚鼠模型中内源性一氧化碳(carbon monoxide,CO)对诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)表达的影响.方法 24只豚鼠以随机数字表法分为4组,每组6只.第1组以生理盐水处理作为正常对照组,第2(AR组)、3、4组以卵清蛋白(ovalbumin,OVA)致敏,制成AR动物模型,第3、4组再分别以血红素氧合酶1(hemeoxygenase 1,HO-1)诱导剂氯化血红素和抑制剂锌原卟啉干预处理,分别作为HO诱导组和HO抑制组,分别测定各组豚鼠血浆中碳氧血红蛋白(carboxyhemoglobin,COHb)的百分含量(用来代表血浆中CO含量),并采用实时荧光定量反转录聚合酶链反应(RT-PCR)法测定鼻黏膜中HO-1和iNOS的相对表达量.结果 第2、3、4组豚鼠AR造模成功.血浆COHb含量(x-±s,以下同)第2组(2.27%±1.13%)高于第1组(1.08%±0.24%),差异有统计学意义(q=4.10,P＜0.01);第3组(3.17%±0.68%)高于第2组,差异有统计学意义(q=3.12,P＜0.05).鼻黏膜中HO-1、iNOS的相对表达量(x-±s,以下同)第2组[分别为(7.80±1.60)×10~(-3)和(5.81±0.05)×10~(-3)]高于第1组[分别为(1.96±0.71)×10~(-3)和(0.97±0.05)×10~(-3)],差异有统计学意义(q值分别为5.52、7.21,P值均＜0.01),第3组[分别为(11.89±4.78)×10~(-3)和(7.42±0.70)×10~(-3)]高于第2组,差异有统计学意义(q值分别为3.86、2.22,P值均＜0.05),第4组[分别为(3.82±0.98)×10~(-3)和(2.34±0.04)×10~(-3)]低于第2组,差异有统计学意义(q值分别为3.76、5.18,P值均＜0.05).结论 内源性CO在AR中影响iNOS的表达.     

变应性鼻炎小鼠鼻黏膜lL-25、lL-33 mRNA表达水平的研究

目的：探讨IL-25 mRNA及IL-33 mRNA在变应性鼻炎小鼠鼻黏膜中的表达及其作用。方法利用Balb/c小鼠建立卵清蛋白致敏的变应性鼻炎小鼠模型,同时使用生理盐水作为对照组,取各组小鼠鼻黏膜组织,使用实时定量PCR法检测两组小鼠鼻黏膜中IL-25 mRNA和IL-33 mRNA的含量。结果IL-25 mRNA和IL-33 mRNA在对照组以及实验组中均有表达,且实验组明显高于对照组,两组比较差异具有统计学意义（P＜0.05）。结论 IL-25和IL-33参与到变应性鼻炎的发病机制中,该结果将有助于提高对变应性鼻炎发病机制的进一步了解,为变应性鼻炎潜在的靶向药物治疗提供了理论依据。     

Th2细胞因子和粘附分子在变应性鼻炎和变应性哮喘发病机制中的作用

目的探讨白细胞介素13(interleukin13,IL-13)、白细胞介素5(interleukin-5,IL-5)和血管细胞粘附分子-1(vascular cellular adhesion mo-lecular-1,VCAM-1)在上下呼吸道变应性炎症一致性中的作用。方法采用6-8周雄性SD大鼠,随机分成变应性鼻炎组10只,鼻炎对照组10只,哮喘组10只和哮喘对照组10只,以卵清蛋白致敏激发制成变应性鼻炎和变应性哮喘模型。HE染色和甲苯胺蓝染色分别检测变应性鼻炎模型鼻粘膜和哮喘模型鼻粘膜及肺组织中嗜酸粒细胞、肥大细胞,免疫组化检测上述组织中IL13、IL-5和VCAM-1的表达。结果变应性鼻炎模型鼻粘膜和变应性哮喘模型肺组织中嗜酸粒细胞、肥大细胞数、VCAM-1和IL-13阳性血管数以及IL-13和IL-5阳性炎症细胞数明显多于相应对照组。结论Th2细胞因子和粘附分子的表达是变应性鼻炎和变应性哮喘共同的机制。     

变应性鼻炎小鼠鼻黏膜白细胞介素-9及其受体mRNA表达水平的研究

目的　探讨白细胞介素9（interleukin-9,IL-9）及其受体IL-9R mRNA在变应性鼻炎小鼠鼻黏膜中的表达及其作用。方法　SPF级Balb/c小鼠16只,随机分为两组,每组8只。实验组卵清蛋白致敏建立变应性鼻炎小鼠模型;对照组使用生理盐水替代。每组随机取4只小鼠,病理检查证明造模成功。每组剩余4只小鼠取其鼻黏膜,实时定量PCR检测小鼠鼻黏膜中IL-9及IL-9R mRNA表达水平。结果  IL-9及IL-9R mRNA在对照组以及实验组中均有表达,实验组小鼠鼻黏膜中IL-9及IL-9R mRNA表达水平均高于对照组（P＜0.05）。小鼠鼻黏膜中IL-9 mRNA表达水平与IL-9RmRNA表达水平呈正相关（r =0.857,P＜0.05）。结论　IL-9及其受体IL-9R参与了变应性鼻炎发生发展中,并起到重要作用,该结果为进一步了解变应性鼻炎发病机制提供了新的视角,为变应性鼻炎靶向药物治疗提供新的线索。     

变应性鼻炎患者血清CD23和CD19表达及其与血清总IgE的关系

目的：探讨变应性鼻炎（AR）患者外周血淋巴细胞CD23、CD19表达及其与血清总IgE、鼻部过敏症状的关系。方法：对46例AR患者进行症状评分后,采用流式细胞术及免疫化学发光法检测其外周血淋巴细胞CD23、CD19表达率和血清总IgE水平,并以32例健康体检者为对照。结果：①AR患者外周血CD23^＋、CD19^＋及CD23^＋／CD19^＋淋巴细胞百分率（^-x±s）分别为11.6±1.9、22.8土3.3和10.2±1.7,分别高于对照组（P〈0.05）。②CD23^＋、CD19^＋、CD23^＋／CD19^＋表达百分率与血清总IgE水平、AR症状评分之间存在正相关。③三者之中以CD23^＋／CD19^＋表达百分率与血清总IgE水平、AR症状评分相关性最强（r值分别为0.65和0.49,P〈0.05）。④CD23^＋／CD19^＋与AR症状评分相关程度优于血清总IgE对应值（r=0.33,P〈0.05）。结论：外周血淋巴细胞CD23、CD19表达参与AR发病,并可能是血清总IgE水平的影响因素,检测CD23^＋／CD19^＋表达率有助于对AR病情的判断。     

IL-16和IL-17在变应性及非变应性鼻炎中的表达水平及意义

目的：检测变应性鼻炎（AR）、非变应性鼻炎（NAR）患者和健康对照者在外周血及鼻分泌物中IL-16和IL-17的表达水平,初步探讨IL—16和IL-17可能参与AR发病的免疫学机制。方法：选取AR患者（AR组）与NAR患者（NAR组）各45例,健康对照者45例（对照组）,所有入组患者均进行过敏原皮肤点刺试验和血清特异性IgE检测。对入组的所有患者进行鼻部症状的视觉模拟量表评分（VAS）。采集患者外周血及鼻腔分泌物,检测其中IL-16和IL-17的表达水平。结果：AR及NAR组患者VAS评分差异无统计学意义（P〉0．05）;在外周血中,AR组中IL-16和IL-17表达水平高于NAR组（P〈O．05）;NAR组中IL-16和IL-17表达水平高于对照组（P〈0．05）。鼻分泌物中,AR组和NAR组中IL-16和IL-17表达均高于对照组（P〈0．05）。结论：IL-16和IL-17可能参与AR的病理过程,具体机制有待进一步探讨。