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Objective To investigate the effects and underlying mechanism of cryptotanshinone (CTS) on early pulmonary fibrosis in mice with lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Methods Forty male C57BL/6J mice (8 weeks old) were randomly divided into control group, model group, treatment group, and CTS group, with 10 mice in each group. A ARDS model was established by intratracheal instillation of LPS (5 mg/kg). The mice in the treatment group was intraperitoneally pretreated with CTS (60 mg/kg) for 3 d before modeling, followed by CTS administion for 7 consecutive days. Similarly, the mice of the control and CTS groups were injected with an equivalent volume of sterile phosphate-buffered saline (PBS) or CTS, respectively. The mice were sacrificed in 24 h after the last challenge, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The injury of lung was observed with HE staining, lung wet-to-dry (W/D) ratio, total protein concentration and total cell number in BALF. The levels of inflammatory cytokines in BALF were determined by enzyme-linked immunosorbent assay (ELISA). The fibrosis of lung was characterized by Masson staining and content of hydroxyproline (HYP). The protein levels of VE-cadherin, CD31, Vimentin and α-smooth muscle actin(α-SMA) were detected by immunohistochemistry or Western blotting. Results Obviously increased lung W/D ratio and total protein concentration and total cell number in BALF, elevated contents of TNF-α, TGF-β1, IL-1β and IL-6 while reduced content of IL-10 in BALF were seen in the model group when compared with the control group (P < 0.05). Compared with the model group, the treatment group had significantly decreased lung W/D ratio and total protein concentration and total cell number in BALF, down-regulated levels of IL-1β, IL-6, TNF-α and TGF-β1 and up-regulated level of IL-10 in BALF (P < 0.05). In addition, CTS also ameliorated lung injury and early fibrosis, decreased lung injury and fibrosis score, and reduced HYP content in LPS-induced ARDS (P < 0.05), up-regulated the VE-cadherin and CD31 levels, and suppressed the Vimentin and α-SMA levels (P < 0.05). Conclusion CTS alleviates LPS-induced early pulmonary fibrosis in ARDS mice, and its underlying mechanism may be related to the inhibition of endothelial-to-mesenchymal transition (EndMT).

Objective To investigate the effect of vitamin D on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the possible mechanism. Methods Forty-five male C57BL/6 mice were randomized equally into control group, LPS group and vitamin D supplement (VD+LPS) group. In VD+LPS group, the mice were given 3 doses of 1, 25(OH)2 vitamin D3 (25 μg/kg) via gavage administrartion at 1, 24 and 48 h before LPS (3 mg/kg) challenge via tracheal intubation, and those in the other 2 groups received lavage with 0.1% dimethylsulfoxide (DMSO) prior to or without LPS challenge. The mice were sacrificed in 2 d after LPS challenge for examination of the total cell count, proportion of neutrophils and protein concentration in the bronchoalveolar lavage fluid (BALF); Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-17A in the BALF. HE staining was used to observe the pathological changes in the lung tissues, and lung edema was assessed by measuring the wet-to-dry ratio (W/D). Flow cytometry was used to analyze the percentage of T helper 17 (Th17) cells in the lungs. Western blotting and quantitative real-time PCR (qPCR) were performed to detect the expression of retinoic acid-related orphan receptor γt (RORγt) in the lung homogenate. Results Pretreatment of the mice with vitamin D prior to LPS stimulation significantly reduced the severity of LPS-induced lung injury. Compared with those in LPS group, the total cell count, percentage of neutrophils, protein concentration, and levels of IL-6, TNF-α and IL-17A in the BALF were all decreased in VD+LPS group (P < 0.05). The percentage of Th17 cells in the lung tissue and the pulmonary expression of RORγt at both the mRNA and protein levels were significantly lower in VD+LPS group than in LPS group (P < 0.05). Conclusion Vitamin D can alleviate LPS-induced ALI in mice possibly by inhibiting pulmonary inflammatory responses mediated by Th17 cells.

Background: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear. Methods: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography. Results: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'‑adenosine monophosphate‑activated protein kinase (p‑AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C). Conclusions: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH. [ABSTRACT FROM AUTHOR]