基于TGF-β1/Smad信号通路探讨白细胞介素13受体α2对变应性鼻炎大鼠鼻黏膜组织重塑的影响

doi:10.6040/j.issn.1673-3770.0.2024.152

摘要/Abstract

摘要： 目的探讨白细胞介素13受体α2(interleukin-13 receptor α2, sIL-13Rα2)对变应性鼻炎(allergic rhinitis, AR)大鼠鼻黏膜组织重塑的影响及相关的可能性机制。方法采用随机数字表法将大鼠分为AR模型组、sIL-13Rα2处理组和对照组,每组各10只。将AR模型组及sIL-13Rα2处理组大鼠以卵清蛋白和氢氧化铝构建Wistar大鼠AR模型后,分别于第4~12周每只每侧鼻腔滴入磷酸盐缓冲液50 μL、sIL-13Rα2 50 μL(100 μg),每周2次。于最后一次滴入结束后24 h取大鼠鼻黏膜组织,HE(hematoxylin-eosin staining)染色观察其病理学变化,RT-PCR(reverse transcription-polymerase chain reaction)检测各组大鼠鼻黏膜组织TGF-β1、Smad2、Smad3和Smad7mRNA水平,Western blotting检测TGF-β1、Smad2、Smad3和Smad7蛋白的表达情况。结果 AR模型组大鼠鼻黏膜肿胀,基底膜增厚,上皮细胞排列紊乱,间质水肿,伴随大量的炎性细胞浸润,而sIL-13Rα2处理组大鼠鼻黏膜上述炎症表现明显减轻。sIL-13Rα2处理组大鼠鼻黏膜组织中TGF-β1、Smad2、Smad3mRNA表达强度明显低于AR模型组(P<0.001,P<0.001,P<0.001);sIL-13Rα2处理组大鼠鼻黏膜组织中Smad7mRNA表达强度明显高于AR模型组(P<0.001)。sIL-13Rα2处理组大鼠鼻黏膜组织中TGF-β1、Smad2、Smad3蛋白表达明显低于AR模型组(P<0.05,P<0.001,P<0.001);sIL-13Rα2处理组大鼠鼻黏膜组织中Smad7蛋白表达明显高于AR模型组(P<0.01)。结论鼻腔滴入IL-13Rα2可通过下调鼻黏膜组织中TGF-β1、Smad2、Smad3的过表达,同时升高Smad7表达,进而明显减轻了AR大鼠鼻黏膜组织重塑。

关键词: 模型动物, 变应性鼻炎, 白细胞介素13受体α2, 转化生长因子β1, Smad, 重塑

Abstract: Objective To investigate the effect of interleukin-13 receptor α2(sIL-13Rα2)on nasal mucosal remodeling in rats with allergic rhinitis(AR)and its possible mechanism. Methods Rats were divided into AR model group, sIL-13Rα2 treatment group and control group by random number table method, 10 rats in each group. After constructing the Wistar rat AR model with ovalbumin and aluminum hydroxide in the AR model group and sIL-13Rα2-treated group of rats, 50 μL of phosphate buffer and 50 μL of sIL-13Rα2(100 μg)were dripped into the nasal cavity on each side of each rat from the 4 th to the 12th week, respectively, twice a week.Nasal mucosa tissues of rats were taken 24 h after the end of the last drop, and were stained with hematoxylin-eosin staining to observe the pathological changes. Reverse Transcription-Polymerase Chain Reaction was used to detect the levels of TGF-β1, Smad2, Smad3 and Smad7 mRNA in the nasal mucosa tissues of rats in each group, and Western blot was used to detect the expression of TGF-β1, Smad2, Smad3 and Smad7 proteins. Results The nasal mucosa of rats in AR model group was swelled, basement membrane thickened, epithelial cells arranged disorderly, interstitial edema, and infiltration of a large number of inflammatory cells, whereas the above inflammatory changes were significantly reduced in sIL-13Rα2 group rats. The intensity of TGF-β1, Smad2 and Smad3 mRNA expression in the nasal mucosa of sIL-13Rα2 group rats was significantly lower than that of AR model group rats(P<0.001, P<0.001, P<0.001).The intensity of Smad7mRNA expression in the nasal mucosa tissue of sIL-13Rα2 group was significantly higher than that of AR model group(P<0.001). The protein expression of TGF-β1, Smad2, and Smad3 in the nasal mucosal tissues of rats in the sIL-13Rα2 treatment group was significantly lower than that in the AR model group(P<0.05, P<0.001, P<0.001). The protein expression of Smad7 in the nasal mucosal tissues of rats in the sIL-13Rα2 treatment group was significantly higher than that in the AR model group(P<0.01). Conclusion Instillation of IL-13Rα2 into nasal cavity can significantly reduce the remodeling of nasal mucosa in AR rats by inhibiting the overexpression of TGF-β1, Smad2 and Smad3 and up-regulating the expression of Smad7 in nasal mucosa.

Key words: Model animals, Allergic rhinitis, Interleukin 13 receptor α2, Transforming growth factor-β1, Smad, Remodeling

中图分类号:

R765

秦娜娜,李玉芬,孙雨浩,魏健,李钦. 基于TGF-β1/Smad信号通路探讨白细胞介素13受体α2对变应性鼻炎大鼠鼻黏膜组织重塑的影响[J]. 山东大学耳鼻喉眼学报, 2025, 39(6): 71-77.

QIN Nana, LI Yufen, SUN Yuhao, WEI Jian, LI Qin. Effect of interleukin-13 receptor-α2 on nasal mucosal remodeling in rats with allergic rhinitis by TGF-β1/Smad signaling pathway[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2025, 39(6): 71-77.

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