布地奈德预防应用对变应性鼻炎大鼠模型IL-4、IL-5的影响

发布时间：2018-05-13 19:03

本文选题：布地奈德 + 最轻持续炎症反应　；参考：《郑州大学》2010年硕士论文

【摘要】： 背景与目的近几年来,人们对于呼吸道变应性疾病的病理机制又有了一些新的认识,“最轻持续性炎症反应”概念的提出就是其中之一,这使得治疗变态反应最佳方案发生了改变,即从缓解临床症状转向根本减轻(或消除)炎症反应。研究显示,无论是常年性变应性鼻炎还是季节性变应性鼻炎患者,当持续接触较低剂量变应原时,即便不出现任何临床症状,但鼻黏膜内变应性炎症仍然存在,主要表现为嗜酸性粒细胞(eosinophils, EOS)的浸润和细胞间粘附分子-1(intercellular adhesion moleculel, ICAM-1)的表达,这种现象被称为最轻持续性炎症反应(minimal persistent inflammation, MPI)。本实验旨在探讨布地奈德预防性应用对变应性鼻炎最轻持续反应大鼠模型鼻粘膜IL-4、工L-5表达的影响。材料与方法 80只健康SD大鼠,雌雄不限,随机分为变应性鼻炎组(A组),实验组(B组),对照组(C组),空白对照组(D组)。A、B、C三组均用卵清白蛋白(OVA)行基础致敏。第3周起,A组、B组和C组大鼠分别给予1%OVA鼻腔激发,25 ul/鼻孔／次,1次／日,共1周；之后改为3次／周,继续激发1周,其余不变。从第6周起,A组仍以1%OVA滴鼻,B组和C组以0.01%OVA滴鼻,共持续三周,D组以生理盐水代替OVA,观察每次激发后30min内大鼠打喷嚏及搔鼻的次数。激发完成后,处死一半A组、B组、C组和D组大鼠,观察鼻粘膜EOS浸润和IL-4、IL-5的表达情况。剩余B组大鼠给予布地奈德(64ug／侧／次,2次／日)治疗2周,剩余A组、C组、D组大鼠给予生理盐水喷鼻,两周后三组大鼠均给予1%OVA滴鼻,每日一次,共一周,激发完成后处死全部大鼠,观察鼻粘膜EOS和IL-4、IL-5表达情况。上述各组数据均用SPSS统计软件进行单因素方差分析并继以最小显著差(LSD)t检验比较组间差异。结果 1.动物症状观察结果：第8周,A组大鼠仍然出现典型喷嚏及搔鼻症状；B组、C组大鼠喷嚏及搔鼻症状明显减轻,甚至消失,与D组大鼠相比无明显差异(P0.05)。药物治疗后再激发过程中,B组变应性鼻炎的症状表现较轻,而A组和C组均出现比较典型的喷嚏和搔鼻症状,B组大鼠平均喷嚏次数与A、C组相比均有显著差异(P0.05)。 2.鼻粘膜HE镜下观察：第8周(模型建立后),B组和C组大鼠鼻粘膜基本完整,杯状细胞和腺体增生较明显,小血管明显扩张。在粘膜层及粘膜下层、微血管和腺体周围,有EOS等炎性细胞浸润。A组大鼠鼻粘膜凌乱,杯状细胞和腺体明显增生,视野中有大量EOS浸润。D组粘膜组织正常,无EOS浸润。A组平均嗜酸性粒细胞计数与B组、C组相比较有明显的差异(P0.05)。药物治疗后,B组大鼠粘膜仅有少量EOS浸润,A组、C组EOS浸润较重,且有明显的杯状细胞和腺体的增生。B组平均嗜酸性粒细胞计数与A组、C组相比较有明显的差异(P0.05)。B组与D组相比无明显差异(P0.05)。 3.鼻粘膜组织免疫组化检测结果：①IL-4阳性信号均分布在上皮细胞、腺体细胞和一些炎性细胞的胞浆中,胞浆着色呈黄色或棕黄色者为阳性细胞,其阳性区的灰度值为：模型建立后,A组灰度值与B组和C组相比较有明显差异(P0.05),B组与C组相比较无明显差异(P0.05)。药物治疗后,B组与A组、C组相比较有明显差异(P0.05),A组与C组相比较无明显差异(P0.05)。②IL-5的阳性分布同上,鼻粘膜组织中IL-5阳性区的灰度值比较结果亦同上结论 1.布地奈德MPI期应用可显著减轻变应性鼻炎大鼠模型症状。 2.布地奈德MPI期应用可显著抑制变应性鼻炎大鼠模型鼻粘膜EOS的浸润。 3.布地奈德MPI期应用可显著抑制变应性鼻炎大鼠模型IL-4、IL-5的表达。
[Abstract]:Background and purpose
In recent years, there have been some new understanding of the pathological mechanism of respiratory allergic diseases. The concept of "the lightest persistent inflammatory response" is one of them, which makes the best plan for the treatment of allergy changes, that is, from relieving the clinical symptoms to the root reduction (or eliminating) the inflammatory response. It is perennial allergic rhinitis or seasonal allergic rhinitis patients. When they continue to contact with low dose allergens, even without any clinical symptoms, allergic inflammation still exists in the nasal mucosa, mainly the infiltration of eosinophils (EOS) and the intercellular adhesion molecule -1 (intercellular adhesion molecule). The expression of L, ICAM-1), which is called the minimal persistent inflammation (MPI), is called the effect of prophylactic use of budesonide on the nasal mucosa IL-4 and the expression of L-5 in the rat model of the lightest and sustained response to allergic rhinitis.
Materials and methods
80 healthy SD rats were randomly divided into the allergic rhinitis group (group A), the experimental group (group B), the control group (group C), the blank control group (group D),.A, B, C three all with ovalbumin (OVA) base sensitization. Third weeks, A, B and C group rats were given nasal excitation, 25 nasal holes / times, 1 times per day for 1 weeks, and then to 3 times. From the sixth week, group A was still using 1%OVA nose drops, group B and group C with 0.01%OVA nose drops for three weeks. Group D was replaced by physiological saline for three weeks. The number of sneezing and scratching in 30min rats was observed every time after each excitation. The remaining B rats were given budesonide (64ug / side / time, 2 / day) for 2 weeks. The remaining A group, C group, D group rats were given saline nasal spray, and three rats were given nasal drops after two weeks, once a week, all rats were killed after the excitation was completed, and the EOS and IL-4 in the nasal mucosa were observed and the expression of IL-5 was observed. The above groups were counted. According to SPSS statistical software, one-way ANOVA was performed, and the difference between groups was compared with the smallest significant difference (LSD) t test.
Result
1. observation of animal symptoms: eighth weeks, group A rats still have typical sneezing and scratching nose symptoms, group B, group C rats' sneezing and scratching nose symptoms obviously reduce, even disappear, compared with group D rats, there is no significant difference (P0.05). In the process of re stimulation after drug treatment, the symptoms of allergic rhinitis in group B are lighter, while the A group and C group have a comparison. Typical sneezing and scratching symptoms, the average sneezing frequency in group B was significantly different from that in group A and C (P0.05).
2. HE under the nasal mucosa: eighth weeks (after the establishment of the model), the nasal mucosa of the rats in group B and C was basically complete. The goblet cells and glands were proliferated more obviously and the small vessels were obviously dilated. In the mucous layer and submucosa, the microvessels and glands were around, and there were EOS and other inflammatory cells in the.A group, the nasal mucosa was in disorder, the goblet cells and glands were obviously proliferated and the field of vision was obviously proliferated. There were a large number of EOS infiltrating.D groups in normal mucous tissue. The average eosinophil count in group.A without EOS infiltration was significantly different from that of group B (P0.05). After drug treatment, there was only a small amount of EOS infiltration in the mucous membrane of B group, A and C group, and the average eosinophil count in the group of goblet cells and glands was obvious. Compared with group A, there was a significant difference in group C (P0.05). There was no significant difference between.B group and D group (P0.05).
3. the immunohistochemical detection results of nasal mucosa tissue: (1) the positive signals of IL-4 were distributed in the epithelial cells. The cytoplasm of the gland cells and some inflammatory cells was yellow or brown as the positive cells. The gray value of the positive region was: after the model was established, the gray value of the A group was significantly different from that of the B group and the C group (P0.05), B and C. There was no significant difference in group phase (P0.05). After drug treatment, there was a significant difference between group B and group A and group C (P0.05). There was no significant difference between group A and C group (P0.05). The positive distribution of IL-5 was similar, and the results of comparison of gray value of IL-5 positive region in nasal mucosa were also the same.
conclusion
1. budesonide MPI phase can significantly reduce the symptoms of allergic rhinitis in rats.
2. budesonide MPI phase can significantly inhibit the infiltration of EOS in nasal mucosa of allergic rhinitis rats.
3. budesonide MPI phase can significantly inhibit the expression of IL-4 and IL-5 in rat models of allergic rhinitis.

【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R765.21

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