Atorvastatin has a protective effect in a mouse model of bronchial asthma through regulating tissue transglutaminase and triggering receptor expressed on myeloid cells-1 expression.

Airway remodeling in asthma contributes to airway hyperreactivity, loss of lung function and persistent symptoms. Current therapies do not adequately treat the structural airway changes associated with asthma. Statin drugs have improved respiratory health and their therapeutic potential in asthma has been tested in clinical trials. However, the mechanism of action of statins in this context has remained elusive. The present study hypothesized that atorvastatin treatment of ovalbumin-exposed mice attenuates early features of airway remodeling via a mevalonate-dependent mechanism. BALB/c mice were sensitized with ovalbumin and atorvastatin was delivered via oral gavage prior to each ovalbumin exposure. Reverse transcription-semi-quantitative polymerase chain reaction (RT-semi-qPCR), ELISA and western blot analysis were used to assess the expression of a number of relevant genes, including tissue transglutaminase (tTG), triggering receptor expressed on myeloid cells (TREM)-1, nuclear factor erythroid 2-related factor (Nrf) 2, hypoxia-inducible factor (HIF)-1α, transforming growth factor (TGF)-ß1, matrix metalloproteinase (MMP)-9 and tissue inhibitors of metalloproteinases (TIMP)-1 in lung tissue. α-Smooth muscle actin (α-SMA) activity was measured by immunohistochemistry. Airway hyperresponsiveness, lung collagen deposition, airway wall area, airway smooth muscle thickness and lung pathology were also assessed. Atorvastatin treatment led to downregulation of tTG and TREM-1 expression in lung tissue after ovalbumin sensitization, blocked the activity of MMP-9, vascular endothelial growth factor, nuclear factor-κB p65, α-SMA, HIF-α and TGF-ß1 and up-regulated Nrf2 expression. Furthermore, the number of lymphocytes and eosinophils in the atorvastatin group was significantly lower than that in the control group. In addition, airway hyperresponsiveness, lung collagen deposition, airway wall area, airway smooth muscle thickness and pathological changes in the lung were significantly decreased in the atorvastatin group, and tumor necrosis factor-α, interleukin (IL)-8, IL-13 and IL-17 in serum were significantly decreased. Histological results demonstrated the attenuating effect of atorvastatin on ovalbumin-induced airway remodeling in asthma. In conclusion, the present study indicated that atorvastatin significantly alleviated ovalbumin-induced airway remodeling in asthma by downregulating tTG and TREM-1 expression. The marked protective effects of atorvastatin suggest its therapeutic potential in ovalbumin-induced airway remodeling in asthma treatment.

Protective effect of Xuebijing injection on D-galactosamine- and lipopolysaccharide-induced acute liver injury in rats through the regulation of p38 MAPK, MMP-9 and HO-1 expression by increasing TIPE2 expression.

Xuebijing injection (XBJ) has long been used to treat infectious diseases in China. The therapeutic effect of XBJ is probably associated with anti-inflammatory effects. However, the precise mechanisms responsible for the effects of XBJ remain unknown. The present study was conducted in order to evaluate the protective effects of XBJ in a rat model of D-galactosamine (D-Gal)- and lipopolysaccharide (LPS)­induced acute liver injury. In the present study, the rats were injected with D-Gal and LPS intraperitoneally to induce acute liver injury. Two hours prior to D-Gal and LPS administration, the treatment group was administered XBJ by intravenous infusion. The effects of XBJ on D-Gal- and LPS-induced expression of tumor necrosis factor (TNF)­alpha­induced protein 8-like 2 (TIPE2), nuclear factor-κB (NF-κB), matrix metalloproteinase-9 (MMP-9) and heme oxygenase-1 (HO-1) as well as mitogen-activated protein kinase (MAPK) signaling was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot analysis, immunofluorescence, as well as by analysing the serum levels of pro-inflammatory cytokines and the transaminases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) levels in the rat liver tissues were also measured. For histological analysis, hematoxylin and eosin (H&E)-stained liver samples were evaluated. The results showed that XBJ upregulated TIPE2 and HO-1 expression, reduced the expression of NF-κB65 and MMP-9, inhibited the LPS-induced gene expression of c-jun N-terminal kinase (JNK) and p38 MAPK, decreased the generation of pro-inflammatory cytokines [interleukin (IL)-6, IL-13 and TNF-α], inhibited ALT and AST activity, and ameliorated D-Gal- and LPS-induced liver injury. The histological results also demonstrated that XBJ attenuated D-Gal- and LPS-induced liver inflammation. It was found that XBJ may prevent LPS-induced pro-inflammatory gene expression through inhibiting the NF-κB and MAPK signaling pathways by upregulating TIPE2 expression, thereby attenuating LPS-induced liver injury in rats. The marked protective effects of XBJ suggest that it has the potential to be used in the treatment of LPS-induced liver injury.