滨蒿内酯对大鼠实验性变应性鼻炎的疗效及机制

Effects of Scoparone on Serum Th17 Ctokines and IL-23 in Rats with Experimental Allergic Rhinitis

目的:探讨滨蒿内酯(Sco)对卵清蛋白(OVA)致敏的变应性鼻炎(AR)模型大鼠血清白细胞介素17(IL-17)、IL-6、肿瘤坏死因子α(TNF-α)和IL-23的影响。方法:32只雄性SD大鼠,随机分为NC组、AR组、Sco组和地塞米松(Dxm)组,后3组大鼠腹腔注射OVA致敏、OVA滴鼻激发建立大鼠AR动物模型;Sco组和Dxm组大鼠在OVA激发建模同时给与相应治疗(Sco 20 m L/kg,Dxm 1 mg/kg);观察各组大鼠行为学改变,取大鼠鼻中隔制片采用苏木精-伊红染色观察鼻黏膜组织学变化,采用ELISA法检测各组大鼠血清IL-23、IL-17、IL-6及TNF-a水平;采用Pearson法分析AR组大鼠症状评分与血清IL-23、IL-17、IL-6及TNF-a的相关性。结果 :NC组偶有搔鼻,AR组大鼠搔鼻、喷嚏及流涕等症状较明显,得分均>5分,表明造模成功;Sco组及Dxm组过敏症状较AR组轻;AR组症状评分明显高于NC组、Sco组和Dxm组(P<0.01);染色结果显示,AR组大鼠鼻黏膜水肿、血管扩张、腺体增生,固有层内可见大量嗜酸性粒细胞浸润,Sco组和Dxm组大鼠鼻黏膜炎性反应较AR组轻;AR组大鼠血清IL-23、IL-17、IL-6及TNF-a水平显著高于NC组、Sco组及Dxm组,Sco组和Dxm组又显著高于NC组(P<0.05);相关性分析结果显示,AR大鼠症状评分与血清IL-23、IL-17、IL-6及TNF-a均呈高度正相关(r=0.774、0.859、0.798、0.721,P<0.01)。结论 :Sco可改变AR模型大鼠的过敏症状,其机制可能是通过下调Th17型细胞因子、IL-23,稳定肥大细胞、减少炎症因子释放、抑制黏液腺分泌而实现。

Objective： To investigate the effect of Scoparone（Sco） on serum IL-17, IL-6, TNF-α and IL-23 in ovalbumin （OVA） sensitized allergic rhinitis （AR） rat model. Methods： 32 male SD rats were randomly divided into NC group, AR group, Sco group and dexamethasone （Dxm） group. Except NC group, the other groups were sensitized by intraperitoneal injection of OVA and OVA nose dropping to establish the AR animal model. In SCO group and Dxm group, the rats were given corre- sponding therapy when they were sensitized by OVA to establish the AR animal model（ Sco 20 mL/kg, Dxm 1 mg/kg）. Behavioral changes of rats in each group were observed. Rats＇nasal septum was collected and made to slice. Hematoxylin eosin staining was used to observe histological changes of the rats＇nasal mucosa and ELISA method was adopted to detect the rat serum IL-23, 1L-17, IL-6 and TNF-αlevels. Pearson method was used to analyze the correlation between symptom scores and serum IL-23, IL-17, IL-6 and TNF--αn AR group. Results： The rats in AR group showed scratching nose, sneezing and runny nose symptoms obviously, and scores were greater than 5, indicating that the model building was successful; The rat in NC Group showed occasional scratching nose, the rat＂ allergy symptoms were lighter in Sco group and Dxm group, and the symptom score in AR group was significantly higher than that of NC group, SCO group and DXM group （P 〈 O. 01 ）. The staining results showed that there were nasal mucosa edema, blood vessel dilation, gland hyperplasia, and a large number of eosinophilic in- filtration within the intrinsic layer in AR group. On the other hand, In Seo group and Dxm group, the nasal mucosa inflammatory reaction was mild. The serum levels of IL-23, IL-17, IL-6, TNF--α in AR group were significantly higher than those in NC group, Sco group and Dxm group, while these indexes in Sco group and Dxm group were significantly higher than those in NC group （ P 〈 0.05 ）. Correlation analysis showed that AR rats symptom score were highly positively correlated with serum IL-23, IL-17, IL-6 and TNF--α （r=0. 774,0. 859,0. 798, 0. 721, P 〈0.01）. Conclusion： SCO can alleviate the allergic symptoms of AR model rats, and the mechanism may be related to down-regulating Thl7 type cytokines and IL-23, stabilizing mast cells, reducing the release of inflammatory factors and inhibiting the secretion of mucus glands.