Experimental studies for botulinum toxin type A to antagonist the VIP/PACAP expression on nasal mucosa in allergic rhinitis rat
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摘要: 目的:探讨血管活性肠肽/垂体腺苷酸环化酶激活多肽(VIP/PACAP)在变应性鼻炎(AR)大鼠鼻黏膜中的表达和意义,以及A型肉毒毒素(BTX-A)对其的抑制作用。方法:将30只SD大鼠随机分为AR组、干预组和对照组。AR组用卵清蛋白致敏健康大鼠,干预组为致敏后应用BTX-A滴鼻7次,对照组用生理盐水滴鼻。观察各组大鼠行为变化、血清IFN-γ及IL-4水平、大鼠鼻黏膜形态变化和VIP/PACAP的表达情况,并进行统计学分析。结果:①AR组大鼠剧烈搔鼻、频繁喷嚏、大量清涕等典型行为评分(7.50±0.50)明显高于干预组(1.00±0.27)和对照组(0.80±0.31),均差异有统计学意义(均P<0.01);②与干预组和对照组比较,AR组大鼠血清IFN-γ降低、IL-4升高、IFN-γ/IL-4比例降低 (均P<0.05)。③与干预组和对照组比较,AR组大鼠鼻黏膜出现纤毛倒伏缺失、炎性细胞浸润、腺腔内炎性细胞渗出明显增多(均P<0.01);干预组上述指标较对照组高;④AR组VIP阳性细胞数(13.27±2.74)高于干预组(5.21±2.18)和对照组(3.56±5.30), PACAP阳性细胞数(20.97±2.14)高于干预组(6.33±3.04)和对照组(4.63±1.25),均差异有统计学意义(均P<0.01);⑤各组间VIP和PACAP的表达量与Thl/Th2细胞浸润均呈负相关(r=-0.340、-0.223,均P<0.05)。结论:大鼠鼻黏膜内VIP/PACAP可能共同参与了AR的发病机制,BTX-A可能通过抑制VIP/PACAP的表达而改善AR的症状。
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关键词:
- 鼻炎 /
- 变应性 /
- 血管活性肠肽 /
- 垂体腺苷酸环化酶激活多肽 /
- 拮抗剂
Abstract: Objective:To explore the expression and significance of vasoactive intestinal peptide and Pituitary adenylate cyclase activiting polypeptide (VIP/PACAP) of nasal mucosa in rats with allergic rhinitis (AR), and the function of botulinum toxin-A(BTX-A) to inhibit the expression of VIP/PACAP in AR.Method:Thirty Sprague-Dawley rats were randomly divided into 3 groups, which were the AR group, the intervention group, and the control group. In the AR group, ovalbumin was used to sensitize healthy rats. In the intervention group, BTX-A was dripped into the nasal cavity of AR rats 7 times. In the control group, only physiological saline was used to drip into the nasal cavity of AR rats. Changes of the rats' behavior were observed. ELISA were used to detected the concentration variation of serum IFN-γ and IL-4. Histopathology and immunohistochemistry were employed to observe morphology in the rats' nasal mucosal and the expression of VIP/PACAP. Statistical analysis was also made.Result:①The typical symptoms marks of nasal scratching, sneezing, nasal blockage and rhinorrhea of AR group(7.5±0.50) were higher than intervention group (1±0.27) and control group (0.8±0.31).②Comparing to intervention group and control group, the serm IFN-γ of the AR group obvious reduced(P<0.05), the serm IL-4 of the AR group obvious rose(P<0.01), and the serm Th1/Th2(IFN-γ/IL-4) of the AR group obvious reduced(P<0.01).③Comparing to intervention group and control group, the cilium loss, inflammatory cells infiltration, and inflammatory cells exudation of nasal mucosa in AR group were more obviously(P<0.01), and theintervention group of the 3 indexes was obviously than control group.④The expression of VIP in the rats' nasal mucosa of the AR group (13.27±2.74) were more intense than intervention group (5.21 ±2.18) and control group(3.56±5.30) (P<0.01),and the expression of PACAP in the rats' nasal mucosa of the AR group (20.97±2.14) were more intense than intervention group (6.33±3.04) and control group(4.63±1.25) (P<0.01).⑤ In all the 3 groups, there was positive correlation between expression of negative in VIP/PACAP and Thl/Th2 cell infiltration(r were respectively -0.340 and -0.223, P<0.05).Conclusion:The VIP/PACAP in the rats' nasal mucosa may play an important role in pathogenesis of AR, and BTX-A could improve the symptoms of AR through inhibition of the expression of VIP/PACAP. -
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