博莱霉素对大鼠肺泡Ⅱ型上皮细胞功能的损伤  

Rat Alveolar Type Ⅱ Injured by Bleomycin

作　　者：孔璐[1] 王志刚[1] 牛建昭[1] 王继峰[1] 金唤[1] 杨美娟[1] 王玲巧[1] 唐炳华[1] 张秋菊[1] 图蘅菁[1] 

机构地区：[1]北京中医药大学细胞生化教研室,北京100029

出　　处：《中国医学科学院学报》2005年第1期81-86,共6页Acta Academiae Medicinae Sinicae

基　　金：国家自然科学基金(30130220);教育部科学技术研究重点项目;中科院化学所胶体与界面重点实验室开放基金(200401)~~

摘　　要：目的探讨博莱霉素(BLM)对肺泡Ⅱ型上皮细胞(AT-Ⅱ)功能的损伤作用。方法向SD大鼠气管内一次性注入BLM复制肺纤维化模型,对照组注入生理盐水,分别于7、14和28d在1.5%戊巴比妥钠麻醉下行支气管肺泡灌洗,膜天平法测定肺表面物质(PS)活性。不同浓度博莱霉素直接刺激培养正常成年大鼠的AT-Ⅱ,荧光定量(FQ)PCR检测AT-Ⅱ表面活性物质蛋白(SP)A、B及水通道蛋白(AQP1)mRNA的表达。结果7d模型组动物出现低氧血症及PS活性明显降低;14d逐渐好转,但仍然低于正常;28d基本恢复正常。BLM刺激AT-Ⅱ组与空白对照组比较,SP-A、SP-B及AQP1mRNA表达均明显降低(P<0.001)。结论博莱霉素具有细胞毒性,可降低AT-Ⅱ分泌的SP-A、SP-B及AQP1mRNA的表达,使PS系统功能异常,从而导致低氧血症及肺水肿的发生。Objective To explore dysfuction mechanism of rat alveolar type Ⅱ(AT-Ⅱ)injured by bleomycin(BLM). Methods SD rats were injected with a single intratracheal dose of bleomycin or control saline. On day 7, 14, and 28 following intratracheal bleomycin or saline instillation, animals were killed under overdose of 1.5% sodium pentobarbital(0.25 ml/100 g, IP)and bronchoalveolar lavage fluid(BALF)from the lung was tested for the activity of pulmonary surfactant(PS)by the Whihelmy Film Balance. Several concentrations of bleomycin stimulated the culture of rat AT-Ⅱ cells, and surfactant protein(SP)A,B, and aquaporin-1(AQP)mRNA were analyzed by fluorescent quantitative polymerase chain reaction(FQ-PCR). Results The activity of PS and hypoxemia significantly decreased on day 7 and improved on day 14 and completely recovered to normal status on day 28. SP-A, B, and AQP-1 mRNA expression in BLM-stimulated group were significantly lower than those in the control group(P < 0.001). Conclusion BLM-injured AT-Ⅱ cells decrease the levels of SP-A, B, and AQP-1 mRNA and cause PS disfunction, resulting in hypoxemia and pneumonedema.

关 键 词：博莱霉素 表面活性物质 大鼠肺泡Ⅱ型上皮细胞 荧光定量PCR 

分 类 号：R979.1[医药卫生—药品] R363[医药卫生—药学]