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. 2015 Feb;36(2):179-87.
doi: 10.1038/aps.2014.112. Epub 2014 Dec 29.

Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice

Min Xu  1 , Fa-le Cao  2 , Yu-fei Zhang  3 , Liang Shan  4 , Xiao-ling Jiang  1 , Xiao-jing An  3 , Wei Xu  1 , Xiu-zhi Liu  1 , Xiao-yan Wang  1
Affiliations

Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice

Min Xu et al. Acta Pharmacol Sin. 2015 Feb.

Abstract

Aim: To study the effects of tanshinone IIA (TIIA) on lipopolysaccharide (LPS)-induced acute lung injury in mice and the underlying mechanisms.

Methods: Mice were injected with LPS (10 mg/kg, i.p.), then treated with TIIA (10 mg/kg, i.p.). Seven hours after LPS injection, the lungs were collected for histological study. Protein, LDH, TNF-α and IL-1β levels in bronchoalveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity in lungs were measured. Cell apoptosis and Bcl-2, caspase-3, NF-κB and HIF-1α expression in lungs were assayed.

Results: LPS caused marked histological changes in lungs, accompanied by significantly increased lung W/D ratio, protein content and LDH level in BALF, and Evans blue leakage. LPS markedly increased neutrophil infiltration in lungs and inflammatory cytokines in BALF. Furthermore, LPS induced cell apoptosis in lungs, as evidenced by increased TUNEL-positive cells, decreased Bcl-2 content and increased cleaved caspase-3 content. Moreover, LPS significantly increased the expression of NF-κB and HIF-1α in lungs. Treatment of LPS-injected mice with TIIA significantly alleviated these pathological changes in lungs.

Conclusion: TIIA alleviates LPS-induced acute lung injury in mice by suppressing inflammatory responses and apoptosis, which is mediated via inhibition of the NF-κB and HIF-1α pathways.

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Figures

Figure 1
Figure 1
The chemical structure of TIIA.
Figure 2
Figure 2
Effects of TIIA on LPS-mediated lung histopathologic changes (H&E stain, ×400). Mice were sacrificed 7 h after LPS injection, and a histopathologic examination of the lungs was performed. (A) Saline control group; (B) TIIA control group; (C) LPS group; (D) LPS/TIIA group.
Figure 3
Figure 3
Effects of TIIA on LPS-induced lung injury. Mice were randomly divided into four groups and all measurements were performed 7 h after LPS injection as described in the Model and Grouping section. (A) BALF LDH; (B) Lung W/D ratio; (C) Evans blue leakage; (D) BALF protein. Values are expressed as mean±SEM. bP<0.05, cP<0.01 vs saline control group. eP<0.05 vs LPS group.
Figure 4
Figure 4
Effects of TIIA on LPS-induced lung inflammatory response. Mice were randomly divided into four groups and all measurements were performed at 7 h after LPS injection as described in the Model and Grouping section. (A) MPO activity in lung homogenates; (B) BALF neutrophils; (C) BALF TNF-α (D) BALF IL-1β. Values are expressed as mean±SEM. cP< 0.01 vs saline control group. eP<0.05, fP<0.01 vs LPS group.
Figure 5
Figure 5
Effects of TIIA on LPS-induced lung apoptosis. Mice were randomly divided into four groups and lungs were harvested 7 h after LPS injection to detect apoptosis by TUNEL staining as described in the Materials and methods section. (A) Saline control group; (B) TIIA control group; (C) LPS group; (D) LPS/TIIA group.
Figure 6
Figure 6
Effects of TIIA on apoptosis-related factors in lungs from LPS-treated mice. Mice were randomly divided into four groups, and lungs were harvested 7 h after LPS injection to detect apoptosis-related factors by Western blot as described in the Materials and methods section. (A) Bcl-2; (B) Caspase-3. Values are expressed as mean±SEM. cP<0.01 vs saline control group. eP<0.05 vs LPS group.
Figure 7
Figure 7
Effects of TIIA on LPS-induced NF-κB and HIF-1α activation. Mice were randomly divided into four groups, and lungs were harvested 7 h after LPS injection to detect the activation of NF-κB and HIF-1α by Western blot as described in the Materials and methods section. (A) NF-κB; (B) HIF-1α. Values are expressed as mean±SEM. cP<0.01 vs saline control group. eP<0.05 vs LPS group.
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