本文選題：布地奈德 + 最輕持續(xù)炎癥反應(yīng)��； 參考：《鄭州大學(xué)》2010年碩士論文

【摘要】： 背景與目的 近幾年來,人們對(duì)于呼吸道變應(yīng)性疾病的病理機(jī)制又有了一些新的認(rèn)識(shí),“最輕持續(xù)性炎癥反應(yīng)”概念的提出就是其中之一,這使得治療變態(tài)反應(yīng)最佳方案發(fā)生了改變,即從緩解臨床癥狀轉(zhuǎn)向根本減輕(或消除)炎癥反應(yīng)。研究顯示,無論是常年性變應(yīng)性鼻炎還是季節(jié)性變應(yīng)性鼻炎患者,當(dāng)持續(xù)接觸較低劑量變應(yīng)原時(shí),即便不出現(xiàn)任何臨床癥狀,但鼻黏膜內(nèi)變應(yīng)性炎癥仍然存在,主要表現(xiàn)為嗜酸性粒細(xì)胞(eosinophils, EOS)的浸潤和細(xì)胞間粘附分子-1(intercellular adhesion moleculel, ICAM-1)的表達(dá),這種現(xiàn)象被稱為最輕持續(xù)性炎癥反應(yīng)(minimal persistent inflammation, MPI)。本實(shí)驗(yàn)旨在探討布地奈德預(yù)防性應(yīng)用對(duì)變應(yīng)性鼻炎最輕持續(xù)反應(yīng)大鼠模型鼻粘膜IL-4、工L-5表達(dá)的影響。 材料與方法 80只健康SD大鼠,雌雄不限,隨機(jī)分為變應(yīng)性鼻炎組(A組),實(shí)驗(yàn)組(B組),對(duì)照組(C組),空白對(duì)照組(D組)。A、B、C三組均用卵清白蛋白(OVA)行基礎(chǔ)致敏。第3周起,A組、B組和C組大鼠分別給予1%OVA鼻腔激發(fā),25 ul/鼻孔／次,1次／日,共1周；之后改為3次／周,繼續(xù)激發(fā)1周,其余不變。從第6周起,A組仍以1%OVA滴鼻,B組和C組以0.01%OVA滴鼻,共持續(xù)三周,D組以生理鹽水代替OVA,觀察每次激發(fā)后30min內(nèi)大鼠打噴嚏及搔鼻的次數(shù)。激發(fā)完成后,處死一半A組、B組、C組和D組大鼠,觀察鼻粘膜EOS浸潤和IL-4、IL-5的表達(dá)情況。剩余B組大鼠給予布地奈德(64ug／側(cè)／次,2次／日)治療2周,剩余A組、C組、D組大鼠給予生理鹽水噴鼻,兩周后三組大鼠均給予1%OVA滴鼻,每日一次,共一周,激發(fā)完成后處死全部大鼠,觀察鼻粘膜EOS和IL-4、IL-5表達(dá)情況。上述各組數(shù)據(jù)均用SPSS統(tǒng)計(jì)軟件進(jìn)行單因素方差分析并繼以最小顯著差(LSD)t檢驗(yàn)比較組間差異。 結(jié)果 1.動(dòng)物癥狀觀察結(jié)果：第8周,A組大鼠仍然出現(xiàn)典型噴嚏及搔鼻癥狀；B組、C組大鼠噴嚏及搔鼻癥狀明顯減輕,甚至消失,與D組大鼠相比無明顯差異(P0.05)。藥物治療后再激發(fā)過程中,B組變應(yīng)性鼻炎的癥狀表現(xiàn)較輕,而A組和C組均出現(xiàn)比較典型的噴嚏和搔鼻癥狀,B組大鼠平均噴嚏次數(shù)與A、C組相比均有顯著差異(P0.05)。 2.鼻粘膜HE鏡下觀察：第8周(模型建立后),B組和C組大鼠鼻粘膜基本完整,杯狀細(xì)胞和腺體增生較明顯,小血管明顯擴(kuò)張。在粘膜層及粘膜下層、微血管和腺體周圍,有EOS等炎性細(xì)胞浸潤。A組大鼠鼻粘膜凌亂,杯狀細(xì)胞和腺體明顯增生,視野中有大量EOS浸潤。D組粘膜組織正常,無EOS浸潤。A組平均嗜酸性粒細(xì)胞計(jì)數(shù)與B組、C組相比較有明顯的差異(P0.05)。藥物治療后,B組大鼠粘膜僅有少量EOS浸潤,A組、C組EOS浸潤較重,且有明顯的杯狀細(xì)胞和腺體的增生。B組平均嗜酸性粒細(xì)胞計(jì)數(shù)與A組、C組相比較有明顯的差異(P0.05)。B組與D組相比無明顯差異(P0.05)。 3.鼻粘膜組織免疫組化檢測結(jié)果：①IL-4陽性信號(hào)均分布在上皮細(xì)胞、腺體細(xì)胞和一些炎性細(xì)胞的胞漿中,胞漿著色呈黃色或棕黃色者為陽性細(xì)胞,其陽性區(qū)的灰度值為：模型建立后,A組灰度值與B組和C組相比較有明顯差異(P0.05),B組與C組相比較無明顯差異(P0.05)。藥物治療后,B組與A組、C組相比較有明顯差異(P0.05),A組與C組相比較無明顯差異(P0.05)。②IL-5的陽性分布同上,鼻粘膜組織中IL-5陽性區(qū)的灰度值比較結(jié)果亦同上 結(jié)論 1.布地奈德MPI期應(yīng)用可顯著減輕變應(yīng)性鼻炎大鼠模型癥狀。 2.布地奈德MPI期應(yīng)用可顯著抑制變應(yīng)性鼻炎大鼠模型鼻粘膜EOS的浸潤。 3.布地奈德MPI期應(yīng)用可顯著抑制變應(yīng)性鼻炎大鼠模型IL-4、IL-5的表達(dá)。
[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.

【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2010
【分類號(hào)】：R765.21

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8 謝燕清;鼻炎的炎癥特征及其與下氣道炎癥及氣道高反應(yīng)性的關(guān)系[D];廣州醫(yī)學(xué)院;2011年

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10 張怡;主動(dòng)吸煙對(duì)變應(yīng)性鼻炎患者的影響[D];武漢大學(xué);2012年

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7 滑[，

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