中医杂志

目的 探讨小青龙汤治疗变应性鼻炎的可能作用机制。方法 45只大鼠随机分为对照组，模型组，氯雷他定组，小青龙汤低、中、高剂量组，麻黄汤合苍耳子散低、中、高剂量组。除对照组外，其余各组大鼠均用卵白蛋白联合氢氧化铝腹腔注射14天建立变应性鼻炎大鼠模型。第14天注射完成后继续用10%卵白蛋白溶液20μl进行鼻部激发以维持模型效果，同时对照组和模型组大鼠给予10 ml·kg^-1·d^-1生理盐水灌胃，氯雷他定组大鼠给予氯雷他定片0.9 mg·kg^-1·d^-1灌胃，小青龙汤低、中、高剂量组分别给予小青龙汤2.7、5.4、10.8 g·kg^-1·d^-1灌胃，麻黄汤合苍耳子散低、中、高剂量组给予麻黄汤合苍耳子散2.43、4.86、9.72 g·kg^-1·d^-1灌胃，每日1次，连续7天。末次灌胃1 h后对各组大鼠进行鼻部症状评分，次日检测大鼠血清免疫球蛋白(IgE)、白细胞介素-4(IL-4)和白细胞介素-13(IL-13)水平；HE染色观察大鼠鼻黏膜组织病理形态；RT-qPCR法和Western Blot法分别检测鼻黏膜胸腺基质淋巴细胞生成素(TSLP)、OX40配体(OX40L)蛋白水平及mRNA表达。结果 与对照组比较，模型组大鼠鼻部症状评分总分升高(P<0.01);HE染色示鼻黏膜纤毛紊乱粘连、基底膜增厚、炎症细胞大量聚集；血清总IgE、IL-4、IL-13水平及鼻黏膜TSLP、OX40L mRNA表达及其蛋白水平均升高(P<0.05或P<0.01)。与模型组比较，各药物干预组大鼠鼻部症状评分总分均降低；氯雷他定组，小青龙汤低、中剂量组，麻黄汤合苍耳子散低、高剂量组大鼠血清总IgE水平均降低，小青龙汤高剂量组和麻黄汤合苍耳子散高剂量组大鼠血清IL-4和IL-13水平降低(P<0.05或P<0.01)；鼻黏膜病理结构改善；除麻黄汤合苍耳子散低剂量组外，其余各药物干预组鼻黏膜TSLP、OX40L mRNA表达均降低(P<0.01)，小青龙汤各剂量组及麻黄汤合苍耳子散中、高剂量组TSLP、OX40L蛋白水平降低(P<0.05)。小青龙汤中剂量组对鼻部症状评分的改善及对TSLP、OX40L mRNA和TSLP蛋白表达的抑制作用优于氯雷他定组(P<0.05)。结论 小青龙汤可能通过抑制大鼠鼻黏膜TSLP/OX40L通路，减轻2型辅助性T细胞(Th2)免疫应答，从而保护大鼠鼻黏膜，发挥治疗变应性鼻炎的作用。

Objective To explore the potential mechanism of Xiaoqinglong Decoction(小青龙汤, XD) in the treatment of allergic rhinitis. Methods Forty-five rats were randomly assigned to a control group, a model group, a loratadine group, low-, medium-and high-dose XD groups, and low-, medium-and high-dose Mahuang Decoction and Cang'erzi Powder(麻黄汤合苍耳子散, MDCP) groups. Except for the control group, rats were administered with ovalbumin(OVA) and aluminum hydroxide via intraperitoneal injection for 14 days to establish an allergic rhinitis model. After the 14 th-day injection, nasal stimulation was continued with 20 μl of 10% OVA solution to maintain the model. Rats in the control group and the model group received 10 ml/(kg·d) of saline, whereas those in the loratadine group were administered with 0. 9 mg/(kg·d) of loratadine. The low-, medium-and high-dose XD groups were administered XD at the dose of 2. 7, 5. 4, and 10. 8 g/(kg·d), respectively. The low-, medium-and high-dose MDCP groups were administered MDCP at the dose of 2. 43, 4. 86, and 9. 72 g/(kg·d), respectively. All treatments were administered by gavage once daily for 7 consecutive days. One hour after the final gavage, nasal symptom scores were recorded for all group of rats. The next day, serum levels of immunoglobulin E(IgE), interleukin-4(IL-4), and interleukin-13(IL-13) were measured. HE staining was used to observe the pathological morphology of the nasal mucosal tissue. Quantitative reverse transcription PCR(RT-qPCR) and Western Blot were performed to assess mRNA and protein expression of thymic stromal lymphopoietin(TSLP) and OX40 ligand(OX40L) in the nasal mucosa. Results Compared to the control group, total nasal symptom score in the model group significantly increased(P<0. 01). HE staining revealed disrupted and adhered cilia, thickened basement membranes, and extensive inflammatory cell infiltration in the nasal mucosa. Serum levels of total IgE, IL-4, and IL-13, as well as TSLP and OX40L mRNA and protein expression in the nasal mucosa, were significantly elevated in the model group(P<0. 05 or P<0. 01). Compared to the model group, the total nasal symptom scores in all drug intervention groups were significantly reduced; the serum total IgE levels in the loratadine group, the low-and medium-dose XD groups, and the low-and high-dose MDCP groups were significantly reduced; and the serum levels of IL-4 and IL-13 in the high-dose XD group and the high-dose MDCP group decreased(P<0. 05 or P<0. 01). Nasal mucosal structure was improved. Except for the low-dose MDCP group, all other intervention groups showed a significant reduction in TSLP and OX40L mRNA expression in the nasal mucosa(P<0. 01). All doses of XD and the medium-and high-dose MDCP groups significantly decreased the protein levels of TSLP and OX40L(P<0. 05). The medium-dose XD group exhibited more improvement of nasal symptom scores and greater suppression of expression of TSLP and OX40L mRNA, and TSLP protein levels compared to the loratadine group(P<0. 05). Conclusion XD may protect nasal mucosa of rats and alleviate allergic rhinitis by suppressing the TSLP/OX40L pathway, thereby attenuating Th2-mediated immune responses.