组胺H4受体及其拮抗剂对变应性鼻炎大鼠的作用研究

目的 通过变应性鼻炎(allergic rhinitis,AR)动物模型,观察组胺H4受体拮抗剂JNJ 7777120对AR大鼠的影响.方法 60只Wistar大鼠以随机数字表法分为5组,每组12只,分别为:正常对照(NC)组、AR模型未处理(AR)组、组胺H1受体拮抗剂氯雷他定处理(HR1)组、组胺H4受体拮抗剂JNJ 7777120处理(HR4)组及组胺H1、H4受体拮抗剂联合处理(HR1+4)组.以卵清蛋白建立大鼠AR模型,比较各组大鼠喷嚏、抓鼻次数、血清总IgE、白细胞介素(interleukin,IL)4、γ干扰素(interferon-γ,IFN-γ)以及及鼻腔灌洗液中趋化因子Eotaxin含量的差异.采用SPSS 13.0软件对数据进行分析.结果 各干预(HR1、HR4、HR1+4)组与AR组相比喷嚏、抓鼻次数、血清总IgE、IL-4、趋化因子Eotaxin含量均显著下降,而IFN-γ显著升高,差异有统计学意义(P值均0.05).HR4组大鼠平均((x)±s,下同)喷嚏、抓鼻次数、血清总IgE、IL-4分别为(29.3±6.5)次、(28.4±7.0)次、(147.67±28.79)mg/ml、(289.05±16.94)Pg/ml,较HR1组的(23.2±5.6)次、(21.4±5.2)次、(100.32±6.00)mg/ml、(267.71±24.26)Pg/ml升高,差异有统计学意义(q值分别为3.72、4.16、8.01、4.96,P值均<0.05),而INF-γ水平在HR4组为(28.17±1.97)pg/ml,低于HRI组的(35.45±1.35)pg/ml,差异有统计学意义(q=3.18,P<0.05).各干预组(HR1、HR4、HRI+4)中Eotaxin含量差异无统计学意义(P=0.096).结论 组胺H4受体拮抗剂JNJ 777120与组胺H1受体拮抗剂氯雷他定同样可以缓解AR症状及炎性反应状态,两者之间未发现有协同作用,JNJ 7777120与氯雷他定相比作用相对较弱.

Effect of histamine H4 receptor and its antagonist on allergic rhinitis in rats

Objective To clarify the effect of histamine H4 receptor antagonist, JNJ 7777120, and histamine H1 receptor antagonist, Loratadine, on allergic rhinitis ( AR) in rats and to study the role of histamine H4 receptor antagonist and histamine H1 receptor antagonist in the pathogenesis of allergic rhinitis and therapeutic value of their antagonist. Methods AR animal model were induced by ovalbumin ( OVA) in the Wistar rats, which treated with histamine H4 receptor antagonist and (or) histamine H1 receptor antagonist. The allergic symptoms (sneezing and nasal rubbing) , serum total IgE and the levels of cytokines in serum or nasal lavage fluid were measured, the diversity between two groups were observed. Statistical analysis was performed using a SPSS 13. 0 software. Results Compared with AR group with no treatment, the inhibition of nasal symptoms ( P < 0. 01), a significant decrease in the levels of IgE, IL-4 in serum and Eotaxin in nasal lavage fluid(P <0. 01), a significant increase in the levels of IFN-μ in serum(P <0. 01 ) after treatment was found. Compared with group treated with Loratadine, inhibition of nasal symptoms (q value were 3.72, 4. 16, P < 0. 01), a significant increase in the levels of IgE and IL-4 in serum (q value were 8. 01, 4. 96, P <0. 05) , a significant decrease in the levels of IFN-γ in serum( q =3. 18, P <0. 05) ingroup treated with JNJ 7777120 also,but no significant differences in the levels of Eotaxin in nasal lavage fluid(P > 0.05). Administration of JNJ 7777120 and Loratadine jointly, neither additive effect nor synergistic action were found ( P > 0. 05). Conclusions Histamine H4 receptor is closely related with allergic rhinitis and is important in the pathogenesis of allergic rhinitis, the same as histamine H1 receptor. Histamine H4 receptor antagonist, JNJ 7777120, could relieve symptoms and inflammatory conditions in allergic rhinitis, the effect was weak compared with Loratadine. Neither additive effect nor synergistic action were found between them.