N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸抗大鼠矽肺纤维化的实验研究

Anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in lung of rat with silicosis

目的探讨N-乙酰基-丝氨酰-天门冬酰-赖氨酰-脯氨酸（AcSDKP）对大鼠矽肺纤维化的拈抗作用。方法实验大鼠随机分为6组，每组10只。矽肺模型对照1组：支气管内灌注生理盐水1ml／只，4周后处死；矽肺模型对照2组：支气管内灌注生理盐水1ml／只，8周后处死；矽肺模型1组：支气管内灌注二氧化硅混悬液1ml／只（每ml含SiO2 50mg），4周后处死；矽肺模型2组：支气管内灌注二氧化硅混悬液1ml／只，8周后处死；矽肺抗纤维化治疗组：支气管内灌注二氧化硅混悬液1ml／只，4周后给予AcSDKP800μg／（kg·d），并持续至第8周处死；矽肺纤维化防治组：给予AcSDKP800μg／（kg·d）48h后，支气管内灌注二氧化硅混悬液1ml／只，8周后处死。采用HE和VG染色对矽肺纤维化病变及其变化特点进行形态学观察。采用羟脯氨酸测定法和Westernblot法对矽肺大鼠肺内胶原含量及其Ⅰ型与川型胶原的表达进行检测。结果抗纤维化治疗组与矽肺模型1组及模型2组相比，矽结节面积下降到84．28％和67．93％，羟脯氨酸含量下降到70．89％和58．18％，Ⅰ型胶原表达量下降到71．08％和58．13％，Ⅲ型胶原表达量下降到80．13％和70．70％，差异均有统计学意义（P〈0．05）；预防治疗组与矽肺模型2组相比，矽结节面积下降到61．13％，羟脯氨酸含量下降到60．27％，Ⅰ型与Ⅲ型胶原表达量分别下降到40．13％和65．77％，差异均有统计学意义（P〈0．05）。结论AcSDKP对二氧化硅刺激的大鼠矽肺纤维化有一定的拮抗作用。

Objective To investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline （AcSDKP） on the collagen synthesis and expression in lung of rats with silicosis. Methods Rats were divided into 6 groups randomly, 10 rats in each group：Control 1 of silicotic model：each rat was intratracheally instilled with 1 ml normal sodium and was killed at the fourth week;Control 2 of silicotic model：each rat was intratracheally instilled with 1 ml normal sodium and was killed at the eighth week;Silicotic model l：each rat was intratracheally instilled with 1 ml silica suspension and was killed at the fourth week;Silicotic model 2：each rat was intratraeheally instilled with 1 ml silica suspension and was killed at the eighth week;Anti-fibrosis treatment of AcSDKP： after each rat was intratracheally instilled with 1 ml silica suspension for 4 weeks,AcSDKP 800 μg/ （kg·d ） was administered into every rat and rats were killed at the eighth week;Preventing fibrosis treatment of AcSDKP：after AcSDKP 800 ~g/（kg＇d） was administered into every rat for 48 hours,each rat was intratracheally instilled with 1 ml silica suspension and rats were killed at the eighth week. Lung fibrosis in morphology was observed by HE and VG staining. Collagen content was detected by hydroxyproline assay. The expression of type Ⅰ and Ⅲ collagen was evaluated by western blot. Results Compared with those of silicotic model 1 and silicotic model 2 group,in anti-fibrosis treatment of AcSDKP group, the area of silicosis nodules decreased to 84.28% and 67.93%, the content of hydroxyproline decreased to 70.89% and 58.18%, the expression of type Ⅰ collagen decreased to 71.08% and 58.13% ,and expression of type Ⅲ collagen decreased to 80.13% and 70.70%. Compared with those of silicotic model 2 group,in preventing fibrosis treatment of AcSDKP group, area of silicosis nodules decreased to 61.13% ,content of hydroxyproline decreased to 60.27% ,and expression of type Ⅰ and type Ⅲ collagen decreased to 40.13% and 65.77%. Conclusion AcSDKP could obviously inhibit the synthesis and expression of collagen in lung of rats with silicosis, which is possibly related with antifibrosis effect of AcSDKP.