沙利度胺对实验性矽肺血管生成的干预研究

STUDY OF ANTIANGIOGENETIC ROLES OF THALIDOMIDE IN EXPERIMENTAL SILICOSIS OF RATS

目的观察实验性矽肺形成过程中肺组织局部血管生成的动态变化,以及沙利度胺对矽肺肺纤维化血管生成的干预作用。方法SD大鼠54只,随机分为3组,矽肺组和沙利度胺组气管内注入二氧化硅混旋液复制实验性大鼠矽肺模型,对照组在相同条件下给予生理盐水。第二天起沙利度胺组给予沙利度胺饲料喂养,其余各组在相同条件下给予普通饲料喂养。采用HE染色、羟脯氨酸含量测定、免疫组织化学染色等方法,观察实验性大鼠矽肺的发病过程,肺组织中p-Akt蛋白和局部血管生成的动态变化及其与肺胶原蛋白含量的关系。结果矽肺组第7天新生血管明显增多,第30天较第7天有所减少,到第60天肺组织正常结构基本消失,取代为广泛结节性纤维化,少见血管;沙利度胺组血管生成在第7天轻于矽肺组,但仍高于对照组。免疫组化显示p-Akt蛋白在矽肺组第7天明显达到高峰,第30天时较第7天有所减弱,第60天时明显减弱。沙利度胺组p-Akt蛋白和羟脯氨酸含量均低于矽肺组,但高于对照组。结论矽肺早期血管生成显著,血管生成在矽肺肺纤维化发生早期可能起重要作用;沙利度胺能在一定程度上抑制过度的血管生成,对实验性矽肺具有一定的阻抑作用。

Objective To observe the dynamic changes of angiogenesis in experimental silicosis of the rat and the antiangiogenetic roles of thalidomide in experimental silicosis. Methods Fifty- four Sprague- Dawley rats were randomly divided into three groups. The silicosis group and the thalidomide group were injected with silic dust suspension endotracheally, while the control group was injected with normal saline instead in the same condition. From the second day the thalidomide group was fed with thalidomide mixed into normal diet, while the other two groups with normal diet instead. Then the following tests were undertaken： （1） HE staining of lung sections; （2） determination lung tissue hydroxyproline （HYP）; （3） immunohistochemical staining of angiogenesis and p-Akt protein in the lung. The dynamic changes of angiogenesis and the connection of angiogenesis and silicosis were observed in different stages. Results In the silicosis group , angiogenesis was significant on day 7 and slightly decreased on day 30. But no angiogenesis could be seen on day 60 , the lung lost its normal structure and silicotic nodules could he seen. Angiogenesis was milder in the thalidomide group compared with that in the silicosis group, but still higher than in the control group on day 7. The expression of p-Akt protein in the lung increased after 7 days in the silicosis group, but slightly decreased on the day 30 and significontly decreased on the day 60. Hydroxyproline concentration and the expression of p-Akt protein were lower in the thalidomide group compared with that in the silicosis group, but still higher than that in the control group. Conclusion Angiogenesis is remarkable in the early stage of silicosis, especially in the early alveolitis phase. Angiogenesis seems to play an important role in the silicosis. Thalidomide can adjust abnormal angiogenesis in the early phase and show the process of silicosis and even stop it.