氨茶碱对哮喘大鼠气道炎症及重塑的影响

摘要

Objective To explore the mechanisms of aminophylline in asthma treatment by measuring nuclear transcription factor-?B( NF-kB) ,interleukin-25(IL-25) and matrix metalloproteinase-9 (MMP-9) changes. Methods 30 Wistar male rats were randomly divided into normal control group ( n = 10), asthmatic model group ( n =10) and aminophylline treatment group in =10). The rat model of asthma was established by intraperitoneal injection (sensitizatian)and nebulization of ovalbnmin( OVA) (challenge). Rats in normal control group were treated with normal saline instead of OVA. The rats of aminophylline treatment group were administered with aminophylline by intraperitoneal injection at a dose of 60 mg/kg before being stimulated by OVA in each time 30 minutes ago. All rats were sacrificed in the last 24 hours after the last challenge. IL-25 levels in serum and the expression of' NF-kB and MMP-9 were detected. Results IL-25. NF-KB and MMP-9 in pulmonary tissue were gradually decreased from asthmatic model group,aminophylline treatment group and normal control group .respectively IL-25 (40. 71 ±3. 87) ng/L, (34. 42± 1,60) ng/L vs C25.69±1.74) ng/L,NF-KB 0. 34±0.03,0. 26±0. 04 vs 0. 16±0.03,MMP-9 0.28± 0. 02,0. 23±0. 02 vs 0.17±0. 01,the difference was statistically significant ( P <0. 01 ). The expression of NF-kB in pulmonary tissue and the concentration of IL-25 in serum and MMP-9 pulmonary tissue had a significant positive correlation r =0. 795, P <0. 01, r =0.881, P <0.01). Conclusion Aminophylline can inhibit the expression of NF-kB in pulmonary tissue and the concentration of IL-25 in serum of asthmatic rats, thus improve inflammatory state. Aminophylline can improve airway remodeling by reducing the expression of NF-kB and MMP-9 in pulmonary tissue.%目的 通过观察哮喘大鼠体内核转录因子κB(nuclear transcription factor-κB,NF-κB)、白细胞介素25(interleukin-25,IL-25)、基质金属蛋白酶9(matrix metalloproteinase-9,MMP-9)的变化,探讨氨茶碱治疗哮喘的作用机制.方法 取30只Wistar雄性大鼠,随机分成正常对照组、哮喘模型组、氨荼碱治疗组各10只.采用卵白蛋白(ovalbumin,OVA)腹腔注射致敏加雾化吸入激发的方法制成哮喘模型,正常对照组大鼠用等量生理盐水取代OVA.氨茶碱治疗组在每次卵蛋白激发前30分钟给予氨荼碱60 mg/kg腹腔注射.分别测定血清中IL-25,肺组织内NF-κB、MMP-9的表达水平.结果 哮喘模型组、氨茶碱治疗组和正常时照组比较,血清IL-25、肺组织NF-κB和MMP-9依次降低,分别为血清IL-25(40.71±3.87)ng/L、(34.42±1.60) ng/L vs (25.69±1.74.) ng/L,肺组织NF-κB 0.34±0.03、0.26±0.04 vs 0.16±0.03,肺组织MMP-9 0.28±0.02、0.23±0.02 vs 0.17±0.01,备组间差异均有统计学意义(P＜0.01).肺组织内NF-κB与血清IL-25和MMP-9均呈显著正相关(r=0.795、0.881,均P＜0.01).结论 ①氨茶碱可明显抑制哮喘大鼠肺组织中NF-κB及血清中IL-25的水平,有效改善哮喘大鼠气道炎症状况.②氨茶碱可能通过降低肺组织中NF-κB、MMP-9的含量,起到改善气道重塑的作用.