PM2.5对变应性鼻炎模型鼻黏膜炎性因子及病理学的影响

Effect of PM2.5 on inflammatory factors and pathology of nasal mucosa in a rat model of allergic rhinitis

目的探讨PM2.5吸入暴露对变应性鼻炎(allergic rhinitis,AR)大鼠模型鼻黏膜炎性细胞因子及组织病理学的影响。方法选取健康雌性SD大鼠24只,采用随机数表法随机分为3组,每组8只,分别为对照组(即NC组)、AR模型组(即AR组)和AR模型PM2.5吸入暴露组(即ARE组)。采用卵清蛋白(ovalbumin,OVA)致敏法制备大鼠AR模型。采用PM2.5的动物吸入性暴露系统进行PM2.5吸入暴露(浓度200 μg/m3),3 h/d,连续30 d。观察大鼠喷嚏、挠鼻及鼻分泌物的量。酶联免疫吸附试验(ELISA)检测血清中OVA特异性IgE及鼻腔灌洗液中炎性因子白细胞介素(interleukin,IL)6、肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)的含量。苏木精-伊红染色观察鼻黏膜组织病理学变化。采用SPSS 17.0软件进行数据分析。结果 ARE组大鼠喷嚏、挠鼻次数及鼻分泌物的量较AR组及NC组明显增加,差异有统计学意义[喷嚏(15.38±1.68)次/15 min比(11.63±1.13)次/15 min比(1.75±0.71)次/15 min,挠鼻(27.75±2.12)次/15 min比(21.25±2.96)次/15 min比(5.25±1.04)次/15 min,鼻分泌物量(18.90±2.07)mg比(13.83±1.81)mg比(3.78±0.41)mg,F值分别为236.089、224.139、183.971,P值均<0.001]。ARE组大鼠血清中OVA特异性IgE及鼻腔灌洗液中IL-6、TNF-α含量较AR组及NC组明显增加,差异有统计学意义[OVA特异性IgE(25.42±2.51)ng/ml比(18.07±1.07)ng/ml比(1.47±0.26)ng/ml,IL-6(123.30±18.86)pg/ml比(63.49±11.29)pg/ml比(16.87±3.29)pg/ml,TNF-α(162.50±38.15)pg/ml比(72.96±11.28)pg/ml比(27.52±4.15)pg/ml,F值分别为481.604、138.277、63.938,P值均<0.001]。NC组大鼠鼻黏膜结构完整,上皮细胞排列整齐;AR组大鼠鼻黏膜上皮细胞排列紊乱,组织结构肿胀;ARE组大鼠鼻黏膜上皮细胞部分脱落,黏膜基底膜增厚,黏膜下组织间质水肿,血管扩张,腺体增生。结论 PM2.5可引起AR大鼠模型鼻黏膜IL-6、TNF-α等炎性因子分泌,促进鼻黏膜病理学损害。

Objective To investigate the effect of PM2.5 exposure on nasal inflammatory cytokines and nasal mucosal pathology in a rat model of allergic rhinitis (AR). Methods Twenty-four healthy female SD rats were randomly divided into 3 groups by random number table method, with 8 rats in each group: normal control group (NC group), ovalbumin (OVA) induced AR model (AR group), and AR model group inhaled to PM2.5 at 200 μg/m3, 3 h/d, for 30 d (ARE group). Nasal symptoms including sneezing, nasal rubs and nasal secretion were recorded. Levels of OVA specific IgE in serum, interleukin 6 (IL-6) and tumor necrosis factor-α(TNF-α) in nasal irrigating solution were measured by enzyme-linked immunosorbent assay (ELISA). The histopathological changes of nasal mucosa were observed by HE staining. SPSS 17.0 software was used to analyze the data. Results The number of sneezing, nasal rubs and the amount of nasal secretion in the ARE group were significantly higher than that in the AR group and the NC group (number of sneezing (15.38±1.68) times/15 min vs (11.63±1.13) times/15 min vs (1.75±0.71) times/15 min, number of nasal rubs (27.75±2.12) times/15 min vs (21.25±2.96) times/15 min vs (5.25±1.04) times/15 min, amount of nasal secretion (18.90±2.07) mg vs (13.83±1.81) mg vs (3.78±0.41) mg, F values was 236.089, 224.139, 183.971, respectively, all P<0.001). Statistically significant differences in OVA specific IgE, IL-6 and TNF-α levels were observed in ARE group exceeded AR group and NC group (OVA specific IgE (25.42±2.51) ng/ml vs (18.07±1.07) ng/ml vs (1.47±0.26) ng/ml, IL-6 (123.30±18.86) pg/ml vs (63.49±11.29) pg/ml vs (16.87±3.29) pg/ml, TNF-α(162.50±38.15) pg/ml vs (72.96±11.28) pg/ml vs (27.52±4.15) pg/ml, F values was 481.604, 138.277, 63.938, respectively, all P<0.001). HE staining showed that the nasal epithelial cells of NC group were intact and neatly arranged. Nasal mucosa epithelial cells were arranged in disorder in AR group, with tissue structure swelling. Partial shedding of nasal epithelial cells, mucosal basement membrane thickening, submucosal tissue interstitial edema, vasodilation and gland hyperplasia were found in ARE group. Conclusion An increase inflammatory factors level such as IL-6 and TNF-α aggravates pathological damage of nasal mucosa in a rat model of AR by exposure to PM2.5.