ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the protective effects of Reduning Injection (, RDN), a patent Chinese medicine, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and its underlying mechanisms of action.</p><p><b>METHODS</b>Sixty male Sprague-Dawley rats were randomly divided into 6 groups, including normal control, model, dexamethasone (DEX, 5 mg/kg), RDN-H (720 mg/kg), RDN-M (360 mg/kg) and RDN-L (180 mg/kg) groups, with 10 rats in each group. Rats were challenged with intravenous injection of LPS 1 h after intraperitoneal treatment with RDN or DEX. At 6 h after LPS challenge, lung tissues and bronchoalveolar lavage fluid (BALF) were collected, and the number of inflammatory cells was determined. The right lungs were collected for histopathologic examination, measurement of gene and protein expressions, superoxide dismutase (SOD) and myeloperoxidase (MPO) activities.</p><p><b>RESULTS</b>In vivo pretreatment of RDN (360, 720 mg/kg) significantly reduced the weight of wet to dry (W/D) ratio of lung, protein content in BALF, and led to remarkable attenuation of LPS-induced histopathological changes in the lungs. Meanwhile, RDN enormously decreased BALF total inflammatory cells, especially neutrophil and macrophage cell numbers. Moreover, RDN increased SOD activity, inhibited MPO activity, alleviated LPS-induced tumor neurosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) expression in lung tissues. Furthermore, RDN (720 mg/kg) efficiently weakened nuclear factorkappa B (NF-κB) gene and protein expression.</p><p><b>CONCLUSION</b>Anti-inflammatory effects of RDN was demonstrated to be preventing pulmonary neutrophil infiltration, lowering MPO activity, TNF-α and iNOS gene expression by inhibiting NF-κB activity in LPS-induced ALI.</p>
Subject(s)
Animals , Male , Acute Lung Injury , Drug Therapy , Pathology , Anti-Inflammatory Agents , Chemistry , Pharmacology , Therapeutic Uses , Bronchoalveolar Lavage Fluid , Cell Biology , Cell Count , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Chemistry , Pharmacology , Therapeutic Uses , Gene Expression Regulation , Injections , Lipopolysaccharides , Lung , Pathology , NF-kappa B , Genetics , Metabolism , Nitric Oxide Synthase Type II , Genetics , Metabolism , Peroxidase , Metabolism , Rats, Sprague-Dawley , Superoxide Dismutase , Metabolism , Tumor Necrosis Factor-alpha , Genetics , MetabolismABSTRACT
To observe the antipyretic effect of Reduning injection (RDN) on lipopolysaccharide (LPS)-induced fever rats and its impact on centric fever medium. Rats were randomly divided into the blank control group, the model group, the Metamizole group, and high and low-dose RDN groups. Except for the blank control group, all of the rats were injected intraperitoneally with LPS (80 microg x kg(-1)) to observe their body temperature changes. The double-antibody sandwich ELSIA method was adopted to determine cAMP content in hypothalamus and MPO in lung tissues of fever peak rats. The high-dose RDN group can obviously reduce the temperature rise in fever rats, and cAMP and MPO content in hypothalamus. RDN showed significant antipyretic effect, which may be related with the reduction of cAMP content in hypothalamus and MPO in lung tissues.