Effect of simvastatin on expression of Toll-like receptor 2 in mouse cyto-megalovirus pneumonia / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effects of simvastatin on the expression of Toll-like receptor 2 ( TLR-2 ) , interferon-γ(IFN-γ) and monocyte chemoattractant protein-1 (MCP-1) in lung tissues of mice with mouse cytomegalovirus ( MCMV) pneumonia and to explore the possible mechanism .METHODS:Male BALB/c mice (6~8 weeks old, n=40) were randomly divided into 5 groups normal control (NC) group, MCMV infection group, simvastatin group 1 (SMV1 group), simvastatin group 2 (SMV2 group), and simvastatin group 3 (SMV3 group).The mice in SMV1, SMV2 and SMV3 groups were gavaged with simvastatin (50 mg· kg-1 · d-1 for 7 d) 7 d before, on the same day of and 3 d after in-traperitoneal injection of MCMV , while the mice in normal control group and MCMV infection group were gavaged with the same volume of normal saline .HE staining was used to observe the pathological changes of lung tissues in mice .Total tis-sue protein was extracted from the lung homogenates to detect the expression of TLR-2 by Western blot and immunohisto-chemical staining .Real-time PCR was used to analyse the content of MCMV DNA .The levels of IFN-γand MCP-1 were measured by enzyme-linked immunosorbent assay (ELISA).RESULTS:Compared with NC group, the pathological chan-ges of the lung tissues of the mice in MCMV group showed alveolar interstitial edema , alveolar wall widening and a large number of inflammatory cells .The expression of TLR-2 in the lung tissues of the mice in model group was increased signifi-cantly.The content of MCMV DNA was increased , and the expression of IFN-γand MCP-1 was also increased significant-ly.Compared with the mice in MCMV group , the pathological changes of the lung tissues of simvastatin groups showed that the inflammatory cells were decreased .The expression of TLR-2 was down-regulated.The content of MCMV DNA was de-creased, and the levels of IFN-γand MCP-1 were also decreased significantly .At the same time, the expression of TLR-2 and the content of MCMV DNA in SMV1 group were less than those in SMV2 and SMV3 groups (P<0.05), and no statis-tically significant difference between SMV 2 and SMV3 groups was observed .CONCLUSION:Simvastatin down-regulates the TLR-2 signaling pathway , and reduces the expression of TLR-2 and replication of MCMV DNA , thus attenuating the pathological damage of the lung tissue .Early intervention with simvastatin plays an important role in preventing the infection of MCMV and reducing the inflammation .