摘要
目的观察大鼠矽肺模型中RNA干扰CD36基因表达对潜在转化生长因子-β1（L—TGF—B．）的活化及矽肺纤维化的抑制作用。方法将Wistar大鼠分为生理盐水组、SiO2模型组（10mgSiO2）、CD36shRNA表达的重组慢病毒（Si02＋IJv—shCD36）组和对照慢病毒（SiO2＋Lv—shCD36一NC）组，每组24只。染尘后7、21、28d处死动物，貂肺上皮细胞增殖抑制实验检测肺泡灌洗液（BALF）中转化生长因子一B，（TGF—p。）的活性；HE和VG染色观察肺组织病理变化；碱裂解法测定肺羟脯氨酸含量。结果染尘7d时，SiO，＋Lv—shCD36组大鼠肺泡巨噬细胞CD36mRNA的表达明显低于生理盐水组、SiO2模型组和SiO2＋lJv—shCD36一NC组，差异有统计学意义（p〈O．05）。SiO2＋Lv．shCD36组大鼠BALF中TGF．13．活化量和活化率均明显低于模型组和SiO2＋lJv—shCD36一NC组，差异有统计学意义（P〈0．05）。染尘28d时，SiO2＋Lv—shCD36组大鼠肺组织可见细胞性矽结节，而模型组和SiO2＋Lv—shCD36-NC组大鼠肺组织可见纤维细胞性矽结节。染尘21d和28d时，SiO2＋Lv—shCD36组大鼠肺羟脯氨酸含量明显低于SiO2模型组和SiO，＋Lv—shCD36-NC组，差异有统计学意义（P〈0．05）。结论大鼠矽肺模型中通过RNA干扰CD36基因表达能够对L—TGF—B，的活化和矽肺纤维化具有一定的抑制作用。
Objective To investigate the inhibitory effects of CD36-targeting RNA interference on the latent transforming growth factorβ1 （L-TGF-β1） activation and silicotic fibrosis in rat silicosis model. Methods Wistar rats were divided into four groups： saline control group （n=24）, SiO2 model group （10 mg SiO2 per rat） （n=24）, SiO2＋Lv-shCD36 group （lentiviral vector expressing specific shRNA against CD36） （n=24）, and SiO2＋Lv-shCD36-NC group （non-silence control lentivirus） （n=24）. At 7, 21, and 28 d after instillation, therats were sacrificed. The activity of TGF-β1 in bronchoalveolar lavage fluid （BALF） was measured by evaluating its inhibitory effect on the proliferation of mink lung epithelial cells. The pathological changes of lung tissue were observed by HE staining and van Gieson staining. The hydroxyproline content in the lungs was determined by alkaline lysis method. Results At 7 d after instillation, the expression of CD36 mRNA in alveolar macrophages was significantly lower in the SiO2＋Lv-shCD36 group than in the saline control group, Si02 model group, and SiO2＋Lv-shCD36-NC group （P〈0.05）; the quantity and percentage of active TGF-β1 in BALF were significantly lower in the SiO2＋Lv-shCD36 group than in the SiO2 model group and SiO2＋Lv-shCD36-NC group （P〈0.05）. At 28 d after instillation, there were cellular silicotic nodules in the lungs of rats in SiO2＋Lv-shCD36 group and fibrotic cellular silicotic nodules in the lungs of rats in SiO2 model group and SiO2＋Lv-shCD36-NC group. At 21 and 28 d after instillation, the hydroxyproline content was significantly lower in the SiO2 ＋Lv- shCD36 group than in the SiO2 model group and SiO2＋Lv-shCD36-NC group （P〈0.05）. Conclusion CD36-targeting RNA interference has inhibitory effects on the L-TGF-βactivation and silicotic fibrosis in rat silicosis model.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
北大核心
2013年第7期518-521,共4页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
国家自然科学基金资助项目（81102106）
关键词
矽肺
抗原
CD36
转化生长因子Β1
纤维化
Silicosis
Antigens, CD36
Transforming growth factor-beta
Pulmonary fibrosis
