摘要
目的 :探讨氟伐他汀对哮喘气道重塑过程的影响及分子机制。方法 :以卵蛋白致敏的豚鼠哮喘模型为对象 ,观察正常对照组、哮喘组及氟伐他汀 +哮喘组之间气道平滑肌肌层厚度的差异。氟伐他汀 +哮喘组即每次激发哮喘前 30min吸入浓度为 0 5g/L的氟伐他汀 2mL。同时采用Dot-blot分子杂交法、免疫组化SABC法检测各组气道ras基因的mRNA和蛋白水平变化。结果 :哮喘组气道平滑肌层平均厚度为 (74 2 7± 3 30 ) μm ,显著高于正常对照组 (38 57± 3 37) μm(P <0 0 1 ) ;氟伐他汀 +哮喘组的平滑肌层厚度为 (51 70± 4 1 3) μm ,明显低于哮喘组 (P<0 0 5)。哮喘组平滑肌细胞的ras基因表达水平明显高于正常对照组 ,但氟伐他汀 +哮喘组未出现该基因的高表达。结论 :氟伐他汀在一定程度上能抑制哮喘气道重塑的病理过程 ,其发挥效应的机制之一是阻断平滑肌细胞rasp2
AIM: To investigate the effects of fluvastatin on the airway remodeling in a guinea pig model of asthma. METHODS: Asthmatic guinea pig model was established by intraabdominal injection of ovalbumin and aluminium hydroxide and challenged with ovalbumin once every other day for 60 days. 30 guinea pigs were randomly divided into three groups: control group ( n= 10), asthma group ( n= 10) and fluvastatin plus asthma group ( n= 10) in which fluvastatin was inhaled at concentration of 0.5 g/L 30 min before every challenging. The thickness of airway smooth muscle layers of every three groups were compared after Haematin-Eosin staining by image analysis system. The level of ras mRNA in airway were examined by Dot-blot molecular hybridization. The expression levels of ras p21 were also examined by immunohistochemical technique. RESULTS: The mean thickness of airway smooth muscle in asthma group was (74 27±3 30) micrometer, greater than that of control group [(38 57±3 37) micrometer ( P< 0 01)]; the airway smooth muscle layer in fluvastatin plus asthma group was thinner than that of asthma group [(51 70±4 13) micrometer ( P< 0 05)]. The transcription and expression level of ras was increased in the muscle layers of asthma group than that of control group. While the transcription and expression of ras in fluvastatin plus asthma group was reduced significantly. CONCLUSION: Fluvastatin could prevent the airway remodeling of asthma guinea pigs through inhibiting the signal transduction mediated by ras p21.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2002年第12期1478-1481,共4页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目 (No .39370 32 5)
关键词
氟伐他汀
哮喘
气道重塑
豚鼠
治疗
Fluvastatin
Asthma
Airway remodeling
Guinea pigs
