积雪草苷对矽肺大鼠NLRP3/IL-1β/IL-18/TGF-β1信号通路的干预作用

Intervention effect of asiaticoside on NLRP3/IL-1β/IL-18/TGF-β1 signal pathway in silicosis rays

关键词: 矽肺  积雪草苷（AS）  NLRP3炎症小体

Keywords: silicosis  asiaticoside（As）  NLRP3 inflammasome

摘 要: 目的 拟从NLRP3/IL-1β/IL-18/TGF-β1通路探讨积雪草苷（asiaticoside，AS）对染矽尘大鼠肺纤维的干预作用，为临床治疗提供理论依据。方法 将32只SD雄性大鼠随机分为对照组、SiO2模型组以及积雪草苷低、高剂量组，每组8只。对照组大鼠经气管灌注1 ml生理盐水，其余各组灌注1 ml SiO2（50 mg/ml）混悬液。造模后的第2天开始灌胃，AS低、高剂量组分别给予40、60 mg/kg AS对照组和模型组给予等量的生理盐水。每天1次，连续给药28 d。于灌胃第28天处死大鼠，取大鼠肺组织行HE、Masson染色观察病理变化，检测大鼠肺组织中羟脯氨酸（HYP）、白介素（IL）-1β、IL-18的含量、I型胶原蛋白（Col-I）、转化生长因子（TGF）-β1和NLRP3、 caspase-1、ASC蛋白表达水平。结果 模型组大鼠肺组织中HYP、IL-18、IL-1β含量均高于对照组（P<0.05），Col-I、TGF-β1、NLRP3、caspase-1、ASC蛋白表达水平亦较对照组明显升高（P<0.05），积雪草苷干预后上述各项指标均较模型组显著降低（P<0.05）。结论 积雪草苷可减轻肺部炎性细胞浸润和肺泡结构的损伤，其机制可能通过NLRP3/IL-1β/IL-18/TGF-β1信号通路进行干预。

Abstract: Objective To investigate the intervention effects of asiaticoside on pulmonary fibrosis in rats through NLRP3/ IL-1β/IL-18/TGF-β1 signal pathway，thereby provide a theoretical basis for clinical treatment. Methods 32 rats were randomly divided into control group，SiO2 model group，high and low does asiaticoside groups，8 rats in each group. Control rats were given 1 ml of normal saline，the other groups rats were given 1 ml 50 mg/ml SiO2 suspension，all by tracheal perfusion. On the second day after modeling，the silica exposed rats of high-does and low-does groups were given 40 mg/kg and 60 mg/kg asiaticoside，respectively，the other rats were given 0.9% normal saline. The rats were sacrificed on the 28th day after perfusion administration，collect the lung for pathological examination by HE and Masson staining，detect the contents of hydroxyproline，interleukin（IL）-1β，interleukin IL-18 and the protein expression levels of Col-I，TGF-β1，NLRP3，caspase-1 and ASC in lung tissues. Results The results showed that the contents of hydroxyproline，IL-18，IL-1β and the expression of Col-I，TGF-β1，NLRP3，caspase-1，ASC in lung tissue of silicosis rats were all higher than those of control group（P<0.05）；after intervention with asiaticoside，the indexes mentioned above were all significantly lower than those in the model group（P<0.05）. Conclusion The results suggested that asiaticoside may improve pulmonary structural damage by silica in silicosis rats，the mechanism may be the positive intervention through NLRP3/IL-1β/IL-18/TGF-β1 pathway.