[Effect of Schisandrin B on mitogen-activated protein kinases and nuclear factor-kappaB in rat lungs exposed to silica].
OBJECTIVE
To investigate the effect of Schisandrin B on mitogen-activated protein kinases (MAPKs) and nuclear factor-KB in rat lungs exposed to silica.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Li
Shu-Fang
SF
Laboratory Animal Center of Shanxi Medical University, Taiyuan 030001, China.
Liu
Tian-Fu
TF
Guo
Min
M
Wang
Zhi-Ping
ZP
Fan
Lin-Hua
LH
D000818:Animals; D034242:Cyclooctanes / Q000494:pharmacology; D005260:Female; D017705:Lignans / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D012822:Silicon Dioxide / Q000633:toxicity*
D034242:Cyclooctanes; D017705:Lignans; D016328:NF-kappa B; D011083:Polycyclic Compounds; C015499:schizandrin B; D012822:Silicon Dioxide; D020928:Mitogen-Activated Protein Kinases