[Interventional effect of asiaticosdide on rats exposed to silica dust].

Objective: To investigate the effect of asiaticoside for fibrosis in lung tissues of rats exposed to silica and to explore its possible mechanism. Methods: 144 SD male rats were randomly divided into control group, model group, positive drug control group, asiaticoside high-dose group, medium-dose group and low-dose group, each group included 24 rats. Rats in the control group were perfused with 1.0 ml of normal saline, and the other groups were given 1.0 ml 50 mg/ml SiO(2) suspension. Gavage of herbal was given from the next day after model establishment, once a day. Rats in the positive drug control group were administration with 30 mg/kg tetrandrine and rats in the low-dose group, medium-dose group and high-dose group were given 20 mg/kg, 40 mg/kg and 60 mg/kg asiaticoside for fibrosis respectively. Rats in the control group and the model group were given 0.9% normal saline. The rats were sacrificed in on the 14th, 28th and 56th day after intragastric administration and collect the lung tissues to detect the content of hydroxyproline, TGF-β(1) and IL-18, observe the pathological changes of the lung tissues by HE and Masson staining and determine the expressions of Col-I, a-SMA, TGF-β in lung tissues by Western Blot. Results: On the 14th day, 28th day and 56th day after model establishment, the lung tissues of rats in the model group showed obvious inflammatory response and accumulation of collagen fibers, and the degree of inflammation and fibrosis increased with time. The intervention of asiaticoside could effectively inhibit the pathological changes of lung tissues. The contents of hydroxyproline, IL-18 and TGF-β1 in lung tissues of model group were higher than those in the control group (P<0.05) , while the level of hydroxyproline, IL-18 and TGF-β1 in asiaticoside groups were significantly decreased, and the difference was statistically signicant (P<0.05) . Compared with the control group, the expression levels of Col-I, TGF-β1and α-SMA in lung tissue of model group were increased (P<0.05) , while the expression level of Col-I, TGF-β1 and α-SMA were decreased after the intervention of asiaticoside, and the difference was statistically signicant (P<0.05) . Conclusion: Asiaticoside can inhibit the increase of Col-I, TGF-β1 and α-SMA content in the SiO(2)-induced lung tissues of rats, reduce the release of TGF-β1 and IL-18 inflammatory factors in lung tissue, and then inhibit the synthesis and deposition of extracellular matrix in rat lung tissue, and improve silicosis fibrosis.目的： 探讨积雪草苷（AS）对染矽尘大鼠肺纤维化的干预作用及可能的作用机制。 方法： 144只雄性SD大鼠随机分为对照组、模型组、阳性药物对照组、AS低、中、高剂量组，每组24只。对照组大鼠气管内灌注1.0 ml生理盐水，其余组灌注1.0 ml 50 mg/ml二氧化硅（SiO(2)）混悬液。造模后第2天给大鼠灌胃，1次/d阳性药物对照组灌注30 mg/kg的汉方己甲素，AS低、中、高剂量组分别灌注20、40和60 mg/kg AS，对照组、模型组灌注等量的生理盐水。于灌胃第14、28、56天分批处死大鼠，取大鼠肺组织，检测肺组织羟脯氨酸（HYP）含量，行HE、MASSON染色，观察肺组织病理学改变，Western Blot测定大鼠肺组织I型胶原蛋白（Col-I）、α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1）的表达，酶联免疫（ELISA）法检测大鼠肺组织中TGF-β1、白细胞介素-18（IL-18）含量。 结果： SiO(2)刺激14、28、56 d后，模型组大鼠肺组织有明显的炎症反应及胶原纤维的积聚，且炎症和纤维化程度随时间加重。造模后第14、28、56天模型组大鼠肺组织中HYP、IL-18和TGF-β1含量均高于对照组（P<0.05），与模型组比较，阳性药物对照组和AS中、高剂量组大鼠肺组织中HYP含量降低；阳性药物对照组和各AS剂量组肺组织中TGF-β1和IL-18含量均降低，差异有统计学意义（P<0.05）；与对照组比较，模型组大鼠肺组织中TGF-β1、Col-I、α-SMA蛋白表达水平升高（P<0.05），与模型组比较，阳性药物对照组和各AS剂量组大鼠肺组织Col-I和α-SMA蛋白表达水平均降低，差异有统计学意义（P<0.05）。 结论： 积雪草苷可以抑制SiO(2)诱导的大鼠肺组织Col-I、TGF-β1、α-SMA含量的升高，减少肺组织中TGF-β1、IL-18炎性因子的释放，抑制大鼠肺组织细胞外基质的合成、沉积，改善矽肺纤维化。.