摘要
目的观察反义金属蛋白酶组织抑制因子-1(TIMP-1)基因转染对大鼠肺纤维化的治疗作用。方法于2005年1月至2006年6月在大连医科大学附属第一医院中心实验室将30只清洁级6周龄雌性SD(Sprague-Dawley)大鼠随机分为5组,即正义TIMP-1转染组、反义TIMP-1转染组、空载体转染组、肺纤维化组、正常对照组,每组6只。正、反义TIMP-1转染组及空载体转染组为在给予博莱霉素(BLM)后第1,3,7,14,28,60,90天将含正、反义人TIMP-1cDNA逆转录病毒载体及空载体导入肺纤维化大鼠肺内,转染28d后处死;肺纤维化对照组仅给予BLM,时间与转染组相同;正常对照组取同期大鼠处死。观察反义TIMP-1基因转染的作用及肺组织羟脯氨酸的变化。结果给予BLM后第1,3天进行反义TIMP-1基因转染,与同一时间点的肺纤维化对照组及空载体转染组比较,纤维化程度减轻,羟脯氨酸含量减少。结论给予BLM后第1,3天进行反义TIMP-1基因转染可以在一定程度上抑制肺纤维化的发展。
Objective To observe the morphologic change in rats with pulmonary fibrosis induced by bleomycin through antisense-human tissue inhibitor of metalloproteinase-1 ( hTIMP-1 ) transfection. Methods Thirty rats were divided into five groups randomly (six rats in each group), namely, hTIMP-1 transfection group, anti-sense hTIMP-1 transfection group, empty retroviral vectors transfection group, pulmonary fibrosis group, and the normal group. On the 1st, 3rd,Tth, 14th, 28th, 60th, 90th day of BLM administration to the hTIMP-1, anti-sense hTIMP-1 and retroviral vectors transfection group, the hTIMP-1 cDNA retroviral vectoi's containing sense and anti-sense ones and the empty vectors were conducted into the lungs of rats with pulmonary fibrosis,which were sacrificed on the 28th days. The pulmonary fibrosis group was given just BLM for the same period of time. The rats in the normal control groups were sacrificed on the same day. Observe the role of anti-sense hTIMP-1 transfection and the change of hydroxyproline. Results The degree of fibrosis and content of HYP were extenuated by antisense hTIMP-1 transfection on 1 st and 3rd day after BLM exposure compared with the same time of fibrosis and transfection by empty retroviral vectors group, morphologically. Conclusion Transfection with antisense- TIMP-1 on the first and third day can suppress the process of pulmonary fibrosis induced by BLM to some extent.
出处
《中国实用内科杂志》
CAS
CSCD
北大核心
2007年第16期1264-1266,共3页
Chinese Journal of Practical Internal Medicine
基金
国家自然科学基金(30370620)