Effect of schisandrin B on lung mRNA expression of transforming growth factor-beta1 signal transduction molecule in rat lungs exposed to silica / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effects of schisandrin B (Sch-B) on expression of transforming growth factor-beta1 (TGF-beta1) and signal transduction molecule mRNA in rat lungs exposed to SiO2, and explore the intervention mechanism of Sch-B on pulmonary fibrosis induced by SiO2.</p><p><b>METHODS</b>Ninety six Wistar rats were randomly divided into control (normal saline) group, SiO2 group and SiO2 plus Sch-B group. The rats were exposed to SiO2 by direct tracheal instillation to establish the silicotic animal models. SiO2 group and SiO2 plus Sch-B group were treated with 1 ml SiO2 (50 mg/ml) for each rat From the first day after model establishment, SiO2 plus Sch-B group were orally given Sch-B (80 mg/kg) a day, control group and silica group were orally given olive oil. On the 3rd, 7th, 14th and 28th days after treatment, 8 rats in each group were sacrificed and samples were collected. The histo-pathological examination of lung was performed by HE staining. The expression levels of TGF-beta1, TGF-betaR II and Smad4 mRNA in the lung tissues were detected by RT-PCR.</p><p><b>RESULTS</b>The results of histo-pathological examination showed that in SiO2 group, lung tissues were injured obviously; the alveolar inflammation with alveolus interval edema and inflammation cell infiltration appeared on the 3rd and 7th days; the alveolus interval became thicker, became thicker, fibroblast and collagen matrix increased markedly on 14th day; the alveolar structure was damaged, alveolar wall thickened obviously, collagen aggravation and pulmonary fibrosis displayed on 28th day. The alveolar inflammation and pulmonary fibrosis in SiO2 plus Sch-B group were significantly less than those in SiO2 group. The expressions levels of TGF-beta1 TGF-betaR II and Smad4 mRNA (TGF-1beta: 1.03 +/- 0.31, 1.33 +/- 0.39,1.08 +/- 0.26, 0.82 +/- 0.16, TGF-betaR II: 0.65 +/- 0.11, 0.80 +/- 0.16, 0.83 +/- 0.24, 0.62 +/- 0.15, Smad4:0.87 +/- 0.15, 0.68 +/- 0.11, 0.78 +/- 0.19, 0.30 +/- 0.08) in SiO2 group were significantly higher than those in the control group (TGF-beta1:0.59 +/- 0.22, 0.55 +/- 0.25, 0.56 +/- 0.20, 0.55 +/- 0.12, TGR-betaR II :0.28 +/- 0.13, 0.31 +/- 0.15, 0.34 +/- 0.15, 0.27 +/- 0.09, Smad4:0.23 +/- 0.11, 0.40 +/- 0.12, 0.39 +/- 0.12, 0.18 +/- 0.06) (P < 0.01 or P < 0.05), but the expression level of TGF-beta1 mRNA was the highest on the 7th day. The expression levels of TGF-beta1 and Smad4 mRNA (TGF-beta1:0.68 +/- 0.28, 0.88 +/- 0.25, 0.75 +/- 0.11, 0.61 +/- 0.14,Smad4:0.25 +/- 0.12, 0.45 +/- 0.09, 0.44 +/- 0.07, 0.21 +/- 0.04) in SiO2 plus Sch-B group were significantly lower than those in SiO2 group (P < 0.01 or P < 0.05 ), but there were no significant differences of the TGFbetaR II mRNA expression levels between SiO2 group and SiO2 plus Sch-B group.</p><p><b>CONCLUSION</b>Sch-B can reduce the pulmonary fibrosis induced by SiO2 through inhibition of the mRNA express of TGF-beta1 and Smad4 in the lung tissue, modulating the TGF-beta1/Smad4 signal transduction pathway and inhibiting the target gene activation.</p>

Effect of Schisandrin B on mitogen-activated protein kinases and nuclear factor-kappaB in rat lungs exposed to silica / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the effect of Schisandrin B on mitogen-activated protein kinases (MAPKs) and nuclear factor-KB in rat lungs exposed to silica.</p><p><b>METHODS</b>92 Wistar rats were randomly divided into four groups: Control (20), Silica (30), Sch-B treated 1 group (Sch-B 1) (24) and Sch-B treated 2 group (Sch-B 2)(18). Silicotic animal models received an intratracheal injection of silica. From the first day after model establishment, rats in Sch-B 1 were treated intragastrically with Sch-B at a dose of 80 mg/kg, once daily. From the 8th day after model establishment, rats in Sch-B 2 were treated intragastrically with Sch-B at a dose of 80 mg/kg, once daily. 6 rats in Sch-B 1 were sacrificed on the 3rd, 7th, 14th and 21st days, and 6 rats in Sch-B 2 on the 14th, 21st and 28th days, 4 Control rats, 6 silica rats on the 3rd, 7th, 14th, 21st and 28th days accordingly, lungs were collected. Right lung for protein extraction, the phosphorylation level of extracellular signal-regulated protein kinase, c-Jun NH2-terminal amino kinase and p38 in lungs were detected by Western Blot. Left lung was fixed by neutral formalin. The ratio of nuclear transfer of NF-kappaB was evaluated by immunohistochemistry.</p><p><b>RESULTS</b>1. The phosphorylation level of ERK1/2 in Sch-B 1 on 3rd, 7th, 14th and 21st (0.974 +/- 0.169, 0.987 +/- 0.149, 0.920 +/- 0.092 and 0.884 +/- 0.078) and Sch-B 2 on 14th, 21st and 28th (1.012 +/- 0.050, 1.167 +/- 0.083 and 1.002 +/- 0.060) were significantly lower than in silica groups P < 0.05 or P < 0.01); The phosphorylation level of JNK1 in Sch-B 1 reached its summit on 7th day (P < 0.01 ), and that in Sch-B 2 on 14th, 21st and 28th (0.882 +/- 0.064, 0.802 +/- 0.061, 0.792 +/- 0.015) was lower than Silica groups at every time points (P < 0.01); The phosphorylation level of p-p38 in Sch-B 1 was higher than silica group on 3rd day (0.309 +/- 0.045) and lower on 7th, 14th and 21st day, but that in Sch-B 2 were lower and lower. 2. The ratio of nuclear transfer of NF-KB in Sch-B 1 on 3rd, 7th, 14th and 21st [(13.54 +/- 5.36)%, (21.01 +/- 6.43)%, (30.55 +/- 6.44)%, (37.39 +/- 9.32)%] was lower than that in silica groups (P < 0.01); but in Sch-B 2, it was lower than silica group on the 21st [(44.33 +/- 22.88)%] and higher on the 28th day [(58.52 +/- 14.57)%] (P < 0.01).</p><p><b>CONCLUSIONS</b>Sch-B has some depression effects on the activation of MAPKs in rat lungs exposed to silica. The nuclear transfer of NF-kappaB could be suppressed by Sch-B in the initial stage of rat lungs exposed to silica. Protection of Sch-B against silica induced lung injury in rats may be via MAPKs and NF-kappaB signal transduction pathway.</p>