Research On Effects Of Schisandrin B Against Silica-induced Lung Injury In Rats

Objective:To evaluate the protective effect of Schisandrin B against silica-induced lung injury in rats and explore its mechanism.Methods:92 Wistar rats were randomly divided into four groups:Control,Silica,Sch-Bâ… and Sch-Bâ…¡.The lung injury model was established by a single intratracheal injection of silica,and the Control Group was injected with the same dose of saline by the same way.After the day of model establishment,rats in Sch-Bâ… Group were treated with Sch-B 80mg/(kg·d),ig,once daily.After 7 day of model establishment,rats in Sch-Bâ…¡Group were treated with Sch-B 80mg/(kg·d),ig,once daily.Control and Silica Groups were treated with corresponding dose of solvent.6 Sch-Bâ… rats were sacrificed after been treated with Sch-B for 3,7,14 and 21days,6 Sch-Bâ…¡rats were sacrificed after been treated with Sch-B for 7,14 and 21days,and 4 control rats,6 silica rats were sacrificed at every time points accordingly,and lungs were collected.The right lungs were used for histopathological studies(HE staining) and the condition of nuclear transfer of NF-κB were assessed by immunohistochemistry(IHC).The left lungs were used to measure the content of hydroxyproline(HYP),malondialdehyde(MDA),glutathione(GSH) and the activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in lung homogenate by a spectrophotometer.The mRNA expression of tumor necrosis factor-alpha (TNF-α) and transforming Growth factor-beta₁(TGF-β₁) were detected by Reverse Transcription Polymerase Chain Reaction(RT-PCR).The phosphorylation level of extracellular signal-regulated protein kinase(ERK),c-Jun NH₂-terminal amino kinase(JNK)and p38 in mitogen-activated protein kinase(MAPK) family in lungs were detected by Western Blot.Results:1.Compared with silica group,Sch-B significantly ameliorated lung tissue histological damage and alleviated the lung index increase,inhibited the HYP content,decreased MDA production,and kept GSH level in the lung homogenate(P＜0.05 or P＜0.01).2.In Sch-Bâ… group,the expression of TNF-αmRNA was higher than control group,it was significant different from control group on the 7^th and 14^th day(P＜0.01) and different from silica group on the 21^st day(P＜0.01);In Sch-Bâ…¡group,it was obviously higher than control group(P＜0.01), it was higher than silica group on the 14^th day(P＜0.01).3.In Sch-Bâ… group,the mRNA expression of TGF-β₁ was higher than control group on the 3^rd day(P＜0.01),but there was no significant difference between silica group and Sch-Bâ… ;In Sch-Bâ…¡group,it was higher than control group(P＜0.01),and higher than silica group on the 14^th(P＜0.01).4.The ratio of nuclear transfer of NF-κB/P65 in Sch-Bâ… group was lower than which in silica groups at every time points(P＜0.01);but in Sch-Bâ…¡group,it was lower than silica group on the 14^th day and higher on the 21^st day(P＜0.01).5.The phosphorylation level of ERK in Sch-Bâ… and Sch-Bâ…¡groups were significantly lower than silica groups(P＜0.05或P＜0.01);The phosphorylation level of JNK1 in Sch-Bâ… reached its summit on 7^th,then lower than Silica groups(P＜0.01), and which in Sch-Bâ…¡were lower than Silica groups at every time points(P＜0.01);The phosphorylation level of p38 in Sch-Bâ… was higher than silica group on 3^rd and lower on 7^th, but which were lower and lower in Sch-Bâ…¡.Conclusions:1.there was protective effect of Sch-B against silica-induced lung injury in rats; Sch-B restrained fibrosis,and had protective effect at both early and later stage that contacted with silica.2.Sch-B could increase the ability of antioxygen,and provide protective effects against silica-induced lung injury.3.The expression of TNF-αand TGF-β₁ mRNA could be regulated by Sch-B.The development of TNF-αand TGF-β₁ mRNA level were different between been treated by Sch-B at the two different stage.4.In the initial stage of rat lungs exposed to silica,the nuclear transfer of NF-κB could be suppressed by Sch-B.5.Sch-B had some depressive effects on the activation of MAPK in rat lungs exposed to silica,and it was most obviously on the activation of ERKs.