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

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、SiO_(2)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 SiO_(2)(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。

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, SiO;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 SiO;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 28 th 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-Ⅰ 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.