沙利度胺对矽肺大鼠肺组织中羟脯氨酸及FIZZ1表达的影响

Effect of thalidomide on expression of hydroxyproline and FIZZ1 in lung tissues of rats with silicosis

目的观察沙利度胺对二氧化硅所致肺纤维化形成的影响。方法SD大鼠54只,随机分为3组,模型组、沙利度胺治疗组和对照组。模型组和沙利度胺治疗组气管内注入二氧化硅混悬液复制实验室大鼠矽肺模型,对照组在相同条件下给予生理盐水。第二天起沙利度胺治疗组给予沙利度胺饲料喂养,其余各组在相同条件下普通饲料喂养。分别在染尘后7、30、60d分批处死大鼠,观察其组织的病理变化,并采用比色法测定肺组织羟脯氨酸含量、免疫组织化学法观察各组大鼠肺组织中FIZZ1(found in inflamm atory zone 1,FIZZ1)蛋白的表达、实时荧光定量PCR法检测FIZZ1mRNA的表达水平。结果沙利度胺治疗组羟脯氨酸含量低于模型组,但高于对照组;FIZZ1蛋白在正常肺组织为弱表达,模型组第7天时表达明显增强,第30天时较第7天时有所减弱,第60天时明显减弱,但强于对照组;沙利度胺治疗组在第7天、第30天及第60天FIZZ1蛋白的表达均较对照组高,但低于模型组,尤其是第7天的表达降低较明显,但第60天降低不甚明显;PCR也显示出同样的结果。结论沙利度胺治疗后减少了矽肺大鼠肺组织中羟脯氨酸的含量,从而抑制胶原形成,对影响矽肺形成有一定的积极作用,但其是否也通过抑制FIZZ1而减轻矽肺的发生尚有待进一步研究。

Objective To explore the effect of thalidomide on pulmonary fibrosis in the rat induced by silicon dioxide. Methods Fifty-four Sprague-Dawley rats were randomly divided into three groups, the silicosis group and thalidomide group were given silicon dioxide suspension endotracheally, while the rats in control group were given physiological saline solution endotracheally. From the second day of administration, the rats in thalidomide group were treated with thalidomide through food. At the 7th, 30th and 60th day after administration, the rats were killed in turn, then the lungs removed and the following examinations were performed： pathological changes by HE staining, levels of hydroxyproline （HYP） in lung, FIZZ1 protein expression in lung were determined by immunohistochemical method, and the expression levels of FIZZ1 mRNA in lung were determined by Realtime-PCR. Results The results showed that the hydroxyproline level in thalidomide group was significantly lower than that in silicosis group, but was significantly higher than that of control group. The expressions of FIZZ1 protein and levels of FIZZ1 mRNA in silicosis group increased significantly from the 7th day after silicon dioxide administration, then gradually decreased but were still higher than that in control at 60th day after silicon dioxide exposure. The expressions of FIZZ1 protein and levels of FIZZ1 mRNA in thalidomide group on the day of 7th, 30th and 60th after silicon dioxide administration were increased too, but all lower than those of silicosis group, especially on 7th day. Conclusions The results suggested that the treatment with thalidomide could decrease the hydroxyproline level in lung of silicosis rats, which might inhibit the progress of silicosis, but if the effects of thalidomide also concerned the inhibition of FIZZ1 expresion, more data seem needed.