Simvastatin attenuates bleomycin-induced pulmonary fibrosis in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Bleomycin-induced fibrosis is extensively used to model aspects of the pathogenesis of interstitial pulmonary fibrosis. This study aimed to determine the benefic effects and mechanisms of simvastatin on bleomycin-induced pulmonary fibrosis in mice.</p><p><b>METHODS</b>Bleomycin-induced pulmonary fibrosis mice were administered with simvastatin in different doses for 28 days. We measured inflammatory response, fibrogenic cytokines and profibrogenic markers in both bleomycin-stimulated and control lungs, and correlated these parameters with pulmonary fibrosis.</p><p><b>RESULTS</b>Simvastatin attenuated the histopathological change of bleomycin-induced pulmonary fibrosis and prevented the increase of lung hydroxyproline content and collagen (I and III) mRNA expression induced by bleomycin. Moreover, simvastatin down-regulated the increased expression of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) induced by bleomycin at both gene and protein levels. Simultaneously, the accumulation of neutrophils and lymphocytes and the increased production of tumor necrosis factor-alpha (TNF-alpha) in bronchial alveolar lavage fluid were inhibited by simvastatin in early inflammatory phase after bleomycin infusion. The higher dose of simvastatin was associated with a more significant reduction in these inflammatory and fibrotic parameters. Furthermore, the inactivation of p38, RhoA and Smad2/3 signaling pathways was observed during simvastatin administration.</p><p><b>CONCLUSIONS</b>Simvastatin attenuated bleomycin-induced pulmonary fibrosis, as indicated by decreases in Ashcroft score and lung collagen accumulation. The inhibitory effect of simvastatin on the progression of pulmonary fibrosis may be demonstrated by reducing inflammatory response and production of TGF-beta1 and CTGF. These findings indicate that simvastatin may be used in the treatment of pulmonary fibrosis.</p>

Simvastatin attenuates lipopolysaccharide-induced airway mucus hypersecretion in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mucus hypersecretion in the respiratory tract and goblet cell metaplasia in the airway epithelium contribute to the morbidity and mortality associated with airway inflammatory diseases. This study aimed to examine the effect and mechanisms of simvastatin on airway mucus hypersecretion in rats treated with lipopolysaccharide (LPS).</p><p><b>METHODS</b>Mucus hypersecretion in rat airways was induced by intra-tracheal instillation of LPS. Rats treated with or without LPS were administered intra-peritoneally simvastatin (5 and 20 mg/kg) for 4 days. Expression of Muc5ac, RhoA and mitogen-activated protein kinases (MAPK) p38 in lung were detected by real-time polymerase chain reaction (PCR), immunohistochemistry or Western blotting. Tumor necrosis factor (TNF)-alpha and IL-8 in bronchoalveolar lavage fluid (BALF) were assayed by an enzyme-linked lectin assay and enzyme linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>Simvastatin attenuated LPS-induced goblet cell hyperplasia in bronchial epithelium and Muc5ac hypersecretion at both the gene and protein levels in lung (P <0.05). Moreover, simvastatin inhibited neutrophil accumulation and the increased concentration of TNF-alpha and IL-8 in BALF follows LPS stimulation (P < 0.05). The higher dose of simvastatin was associated with a more significant reduction in Muc5ac mRNA expression, neutrophil accumulation and inflammatory cytokine release. Simultaneously, the increased expression of RhoA and p38 MAPK were observed in LPS-treated lung (P <0.05). Simvastatin inhibited the expression of RhoA and p38 phosphorylation in lung following LPS stimulation (P < 0.05). However, the increased expression of p38 protein in LPS-treated lung was not affected by simvastatin administration.</p><p><b>CONCLUSIONS</b>Simvastatin attenuates airway mucus hypersecretion and pulmonary inflammatory damage induced by LPS. The inhibitory effect of simvastatin on airway mucus hypersecretion may be through, at least in part, the suppression of neutrophil accumulation and inflammatory cytokine release via inactivation of RhoA and p38 signaling pathway.</p>

Effects of delayed opening of infarct-related artery on late left ventricular remodeling in patients with acute anterior myocardial infarction / 中华心血管病杂志

<p><b>OBJECTIVE</b>To assess the effect of delayed opening of the infarct-related artery (IRA) by percutaneous coronary intervention (PCI) on the late left ventricular remodeling after acute anterior myocardial infarction (AAMI).</p><p><b>METHODS</b>Sixty four patients with initial Q-wave AAMI and with the total occluded IRA conformed by angiogram at 9.1 +/- 2.3 (2 - 14) days after the onset were divided into successful PCI group and control group (not receiving PCI or the IRA not re-opened). Two-D echocardiogram was performed at acute phase (about 3 weeks), 2 and 6 months after onset of AAMI respectively to detect the left ventricular function and left ventricular wall motion abnormality (VWMA). The total congestive heart failure events were recorded during 6 months follow-up.</p><p><b>RESULTS</b>VWMA scores, left ventricular ejection fraction (LVEF), left ventricular end-diastolic and end-systolic volume indexes (LVEDVI and LVESVI) were similar in 2 groups at acute phase and 2 months after the onset of AAMI. There were no differences between the parameters above at acute phase and 2 months in each group too. VWMA scores and LVEF did not changed significantly at 6 months in each group compared with those at acute phase and 2 months (P > 0.05). But LVEDVI and LVESVI were significantly smaller in the successful PCI group than those in the control group (P < 0.01, P < 0.05). The rate of congestive heart failure events was 19% in control group and 2.0% in successful PCI group (P > 0.05) respectively.</p><p><b>CONCLUSIONS</b>Delayed opening of IRA in AAMI could prevent the late phase but not the early phase of left ventricular remodeling after AMI.</p>