坎地沙坦对染尘大鼠肺纤维化的影响  

Studying the influence of Candesartan cilexetil on the lung fibrosis in rats exposed to silica

作　　者：尹刚[1] 朱为勇[1] 张华[2] 李越凡[1] 张春玲[3] 

机构地区：[1]青岛大学医学院第二附属医院,青岛市中心医院心内科,266042 [2]青岛大学医学院第二附属医院职业病科266042 [3]青岛大学医学院第二附属医院呼吸内科,266042

出　　处：《中华劳动卫生职业病杂志》2012年第4期250-254,共5页Chinese Journal of Industrial Hygiene and Occupational Diseases

摘　　要：目的观察坎地沙坦对染尘大鼠矽肺形成过程中血管紧张素Ⅱ（AngⅡ）、肺纤维化及细胞因子的影响。方法将Wistar大鼠随机分为模型组、干预组、对照组，每组32只。干预组每天灌胃坎地沙坦10mg／kg，模型组和对照组同法给予等量生理盐水；灌胃1周后，模型组和干预组水合氯醛腹腔注射麻醉，将0．5ml矽尘混悬液（浓度为50mg／ml）缓慢注入气管，对照组大鼠气管内注入0．5ml灭菌生理盐水。染尘后第2天，各组大鼠恢复先前的处理后第3、7、14、28天各处死大鼠8只。计算肺脏系数并进行肺组织HE及Masson染色观察；用免疫组化方法测定肺组织血管紧张素转化酶（ACE）表达水平；用ELISA测定肺泡灌洗液中转化生长因子β1（TGF峨）及AngⅡ含量。结果干预组大鼠第3、7、14、28天肺泡炎症和纤维化程度均较模型组明显减轻，干预组大鼠肺脏系数明显低于模型组，差异有统计学意义（P〈0．01）。与对照组比较，模型组和干预组肺泡灌洗液中TGF-β．和AngⅡ含量均明显升高，差异有统计学意义（P〈0．01）：与模型组比较，干预组肺泡灌洗液中TGF-β。和AngⅡ含量均明显降低，差异有统计学意义（P〈0．01）。模型组和干预组肺组织ACE表达明显高于对照组，干预组肺组织ACE表达明显低于模型组，差异均有统计学意义（P〈0．01）。结论早期使用坎地沙坦干预能够明显减轻染尘大鼠的肺组织炎症和肺纤维化程度，降低肺泡灌洗液中的TGF-β．和AngⅡ含量，下调肺组织中ACE表达。Objective To explore the effects of Candesartan cilexetil on the rats exposed to silica. Method Ninety-six wistar rats were randomly divided into model-group, intervention-group and control-group （32 rats a group）. The intervention-group, model-group and control group were orally exposed to Candesartan cilexefi （ 10 mg/kg） and normal solution for a week, respectively. Then the model and intervention groups were exposed to silica by intratrachea] infusion of silica dust suspension （50 mg/ml）, the control group was exposed to 0.5 ml normal solution for 2 days. On the 3rd , 7th ,14th and 28th days after exposure to silica, 8 rats of each group were sacrificed, respectively. The samples of lung tissues were collected. The lung/body coefficients were detected. The pathological examinations were performed by HE and Masson staining. The levels of ACE in the lung tissues were observed by immunoehemistry staining. The levels of TGF-β1 and Ang II in the BALF were examined by ELISA. Results On the 3rd, 7th ,14th and 28th days after exposure, the levels of alveolitis and pulmonary fibrosis in the intervention group were significantly alleviated as compared with model group, and the lungPnody coefficients in the intervention group, which were significantly lower than those in model group re- spectively （P〈0.01）. As compared with control group, the levels of TGF-β1 and Ang II of the BALF in the model and intervention groups significantly enhaneed （P〈0.O1）. As compared with model group, the levels of TGF-β1 and Ang Ⅱ of the BALF in the intervention group significantly decreased （P〈0.01）. As compared with control group, the levels of ACE of the lung tissues in the model and intervention groups significantly increased （P〈 0.01 ）. But the level of ACE of the lung tissues in the intervention group was significantly lower than thai in the model group （P〈0.01）. Conclusion The early Candesartan cilexetil intervention could signifieantly deerease the levels of alveolitis and lung fibrosis,

关 键 词：矽肺 坎地沙坦 转化生长因子Β 血管紧张素类 

分 类 号：R135.2[医药卫生—劳动卫生]