摘要
目的探讨波生坦对肺纤维化大鼠肺胶原沉积与MMP-9、TIMP-1的影响。方法将48只成年雄性Wistar大鼠随机均分为6组:对照2周组、4周组(C2组、C4组),模型2周组、4周组(M2组、M4组)及治疗组(T1组、T2组)。予博莱霉素建模,T1、T2组分别于第2 d、第15 d始每天予波生坦灌胃至第28 d。Masson染色观察肺胶原沉积情况,用酶联免疫反应法测定肺泡灌洗液的MMP-9、TIMP-1浓度。结果 (1)C2组、C4组大鼠肺间质胶原稀少;M2组可见大量淡蓝色胶原沉积,M4组明显加重伴部分纤维化;T1组较M4组显著减少,T2组较M4组无差异。(2)造模后MMP-9浓度随时间升高:C2组、C4组、M2组、M4组分别为(1.15±0.27)μg/m L、(1.23±0.31)μg/m L、(1.98±0.35)μg/m L、(2.38±0.47)μg/m L,T1组较M4组显著下降(P<0.05)。(3)M2组、M4组TIMP-1浓度明显高于C2组、C4组,T1组较M4组明显下降,差异有统计学意义。结论波生坦可减少肺纤维化大鼠肺组织的胶原沉积,可能是通过早期抑制MMP-9、TIMP-1途径起作用。
Objective To observe the effect of bosentan on collagen deposition and MMP- 9 / TIMP- 1 of pulmonary fibrosis（ PF）.Methods 48 male adult Wistar rats were randomly and equally divided into control groups（ C2,C4 group）,model groups（ M2,M4 group）and treated groups（ T1,T2 group）. Bleomycin was used to create PF models. The collagen deposition in lung was observed by Masson＇s trichrome stain,and the level of MMP- 9 and TIMP- 1 in BALF were measured by ELISA. Results（ 1） There was less collagen deposition in C2 and C4 groups. Light blue collagen deposition could be seen in M2 group. M4 group showed significant serious fibrosis. T1 group was significantly less than M4 group,and there was no significant difference between T2 and M4.（ 2） MMP- 9 expression was increased in C2,C4,M2 and M4 groups [（ 1. 15 ± 0. 27）,（ 1. 23 ± 0. 31）,（ 1. 98 ± 0. 35） 、（ 2. 38 ± 0. 47） ng / m L],which were significantly lower than in T1 group than M4. The level of TIMP- 1 was higher in M2 and M4 groups（ P〈0. 05）.（ 3） TIMP- 1 in M2 and M4 groups was significantly higher than C2,C4 and T1 groups,and significantly lower than M4 group. There was statistical significance. Conclusion Bosentan can alleviate the collagen deposition in lung of pulmonary fibrosis in rats,and inhibit the expressions of MMP- 9 / TIMP- 1 in early stage.
出处
《黑龙江医学》
2015年第6期598-599,共2页
Heilongjiang Medical Journal
基金
广东省科技厅科技计划项目(2013B021800045)
