β-葡聚糖抑制大鼠硅肺纤维化损伤的机制研究

The mechanism study of β-glucan on inhibiting lung fibrosis in rats induced by SiO_2

目的探讨β-葡聚糖通过对氧化应激的调节,抑制大鼠硅肺纤维化的作用及其机制。方法采用动式染尘法制作大鼠硅肺模型,实验分组为:对照组、模型组、β-葡聚糖前处理组、β-葡聚糖后处理组。HE染色观察肺组织病理形态,检测各组大鼠肺组织及血清的丙二醛(MDA)表达、过氧化氢酶(CAT)以及还原型谷胱甘肽(GSH)表达;采用Western blot法检测肺组织内I型胶原、α-平滑肌肌动蛋白(α-SMA)、硫氧还蛋白-1(TRX-1)的表达。结果与对照组相比,模型组有典型的矽结节形成,α-SMA阳性染色明显,而β-葡聚糖前、后处理组均能够显著抑制大鼠肺纤维化程度。与对照组相比,模型组肺组织、血清中MDA含量明显上调,而血清中CAT及肺组织中GSH含量增高,同时伴有I型胶原、α-SMA蛋白水平的上调和TRX-1蛋白水平的下调(P<0.05);而予以β-葡聚糖前处理和后处理,均能够显著抑制二氧化硅引起的上述病变,差异有统计学意义(P<0.05)。结论β-葡聚糖可能通过上调TRX-1表达,拮抗氧化应激损伤,从而抑制硅肺纤维化的发生与发展。

Objective To investigate the effect of β-glucan on the inhibition of pulmonary fibrosis in rats and potential oxidative stress mechanism. Methods Silicotic model was made by inhaled SiO_2 in a dynamic manner. Rats were divided into four groups： control group,silicosis group,β-glucan pre-treatment and post-treatment group. The pathological morphology of lung was observed by HE staining. The levels of MDA,CAT and GSH in lung tissue or in serum were measured for evaluating the degree of oxidative stress. The expression of collagen type I,α-SMA and TRX-1 were detected by Western blot. Results Compared with control group,the silicotic lesions were observed in rats exposed to silica with positive expression of α-SMA. Pre-treatment and post-treatment with β-glucan could alleviate the pathologic changes in silicotic group. The level of MDA in lung and serum were increased accompanied with down-regulation of CAT in serum and GSH in lung tissue of silicotic group. Moreover,the expression of collagen type I and α-SMA in silicotic group were higher than those in control group with down-regulation of TRX-1（ P〈0. 05）. Pre-treatment and post-treatment with β-glucan could alleviate all these changes in rats exposed to SiO_2（ P〈0. 05）. Conclusion β-glucan may inhibit the development and progression of pulmonary fibrosis by up-regulating TRX-1 expression and anti-oxidative stress injury.