Interventional effect of asiaticosdide on rats exposed to silica dust / 中华劳动卫生职业病杂志

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.

Therapeutic effect of tetrandrine on silicosis rats and its toxic effect on liver and kidney function / 中国职业医学

OBJECTIVE: To explore the therapeutic effect of tetrandrine(TET) on silicosis model rats and its toxic effect on liver and kidney function. METHODS: The specific pathogen free healthy male Wistar rats were randomly divided into the control group, the model group and the TET group, with 14 rats in each group. By un-exposure tracheal injection method, the rats in the model and TET groups were given one-time tracheal infusion of free silicon dioxide suspension with a mass concentration of 50 g/L to establish the rat model of silicosis. Rats in the control group were infused with 1 mL of 0.9% sodium chloride solution with the same method. On the second day after the model was established, the TET group was given 30 mg/kg body mass of TET solution by gavage. The other two groups were given the same amount of 0.9% sodium chloride solution. The treatment was once per day, six times per week. Seven rats in each group were sacrificed on the 28 th and 56 th days after modeling. The morphological change of the lung, liver and kidney tissues of each group was observed. The enzyme-linked immunosorbent assay was used to detect the level of tumor necrosis factor-α(TNF-α), transforming growth factor-β1(TGF-β1), interleukin(IL)-1β and IL-6, in the lung tissues of rats in each group. The activities of aminotransferase(ALT), aspartate aminotransferase(AST) and the levels blood urea nitrogen(BUN), creatinine(CRE) were detected by automatic biochemical analyzer. RESULTS: The lung organ coefficients of rats in the TET group were lower than those of the model group on the 28 th and 56 th days(all P<0.05). The lung organ coefficient of the rats in the TET group on the 56 th day was higher than that in the same group on the 28 th day(P<0.05). The lung tissue structure of the control group was normal. After modeling, the lung tissues of rats in model group showed different degrees of pathological changes such as alveolar structure destruction, inflammatory cell infiltration, and fibrosis on the 28 th and 56 th days. The degree of pathological changes in TET group was less than that of the model group. In the lung tissues of rats in the model group, the levels of TNF-α, TGF-β1, IL-1β and IL-6 were higher than those of the control group(all P<0.01). The levels of TNF-α, TGF-β1, IL-1β and IL-6 in the lung tissues of rats in the TET group were lower than that of the model group(all P<0.01), but there was no statistically significant difference when compared with the control group(all P>0.05). The activities of ALT and AST in the TET group were higher than those in the model group and the control group(all P<0.01). The level of serum BUN in TET group was higher than that in control group(P<0.01), but it showed no statistical difference when compared with the control group(P>0.05). The level of serum CRE in each group showed no significant difference(P>0.05). There were no abnormal pathological changes found in the liver and kidney tissues of rats in each group at different times. CONCLUSION: TET can reduce the inflammatory response in silicosis rats and improve lung tissue fibrosis; however, the therapeutic dose may have certain toxicity to the liver and kidney of the silicosis rats.