title: Tanshinone IIA suppresses lung injury and apoptosis, and modulates protein kinase B and extracellular signal-regulated protein kinase pathways in rats challenged with seawater exposure.
abstract: 1. Tanshinone IIA (TIIA) is one of the main active components of the Chinese herb, Danshen. In the present study, we investigated the role of apoptosis in seawater exposure-induced acute lung injury (ALI), and explored the effects of TIIA on lung injury, apoptosis, and protein kinase B (Akt) and extracellular signal-regulated protein kinase (ERK) pathways in seawater-challenged rats. The rats were randomly divided into four groups: (i) naive group, no drug was given; (ii) TIIA control group, TIIA (50 mg/kg) was given intraperitoneally; (iii) seawater (SW) group, seawater (4 mL/kg) was given; and (iv) TIIA/SW group, TIIA (50 mg/kg) was injected intraperitoneally 10 min after seawater instillation. 2. The results showed that TIIA treatment significantly improved seawater exposure-induced lung histopathological changes, alleviated the decrease in PaO(2) , and reduced lung oedema, vascular leakage and cell infiltration. As shown by terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) assay, seawater exposure induced apoptosis in lung tissue cells. Furthermore, seawater exposure also changed apoptosis-related factors Bcl-2 and caspase-3, and caused a reduction in the activation of Akt and ERK1/2 pathways. Furthermore, TIIA treatment decreased the number of apoptotic cells, reversed changes in Bcl-2 and caspase-3, and upregulated the activation of Akt and ERK1/2 in seawater-challenged rats. 3. In conclusion, the data suggest that apoptosis might play an important role in seawater exposure-induced lung injury and that TIIA could significantly attenuate the severity of ALI and apoptosis in seawater-challenged rats, which is possibly through modulation of Akt and ERK1/2 pathways.
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Jia-Huan
authors.initials: JH
authors.lastname: Li
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Xie
authors.forename: Qi-Xin
authors.initials: QX
authors.lastname: Fan
authors.forename: De-Guang
authors.initials: DG
authors.lastname: Mu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Fa-Le
authors.initials: FL
authors.lastname: Cao
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Wang
authors.forename: Peng-Tao
authors.initials: PT
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Fa-Guang
authors.initials: FG
authors.lastname: Jin
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Li
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D010313:Partial Pressure; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012623:Seawater; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D045784:Abietanes; C494821:Bad protein, rat; D051025:bcl-Associated Death Protein; C021751:tanshinone; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D053148:Caspase 3; D010100:Oxygen