The Effect Of Group Ⅱ Metabortropic Glutamate Receptors In The Lipopolysaccharide-induced Lung Injury

Group II metabotropic glutamate receptors(II mGluRs), including mGluR2 and mGluR3, are G protein-coupled receptors,. In the nervous system, II mGluRs as presynaptic receptors, play a negative feedback regulation on the release of glutamate. Experiments show that, II mGluRs activation can promote the absorption of glutamate to reduce the neurotoxicity induced by endotoxin. But II mGluRs activation on the impact of LPS-induced acute lung injury have not been reported. In order to further reveal the mechanisms of Glu effects on the lungs, mGluR2/3 expression and distribution in mouse lung tissue, the Glu releasing and the role of IlmGluRs antagonist LY341495 on acute lung injury induced by LPS were observed in this study.Objective:To investigate the expression of group II metabotropic glutamate receptors in lung tissue, and the role of it played in lung injury induced by endotoxin. Influence of LPS on Glu Content in Bronchoalveolar Lavage Fluid in vivo was observed to reveal the cellular sources of high Glu concentration in LPS-induced ALI. To investigate the possible pathophysiological mechanism of glutamate in lung injury induced by endotoxin, and the possible protective role of LY341495, a specific glutamate IImGluRs antagonist, on LPS induced ALIMethods:mGluR2/3 expression in mice lung tissue were analyzed by SABC immunohistologic, Immuno-fluorescence methods and fluorescence real-time RT-PCR. Acute lung injury models in mice were created by injecting LPS(10mg/kg) into abdominal cavity, the concentration of amino acids in the BALF was measured with high-performance liquid chromatography(HPLC), the wet-to-dry weight of lung ratio was calculated after measurement, the MPO activity,NO concentration NOS(iNOS) activity,MDA concentration and SOD activity in lung homogenate were detected by biochemistry methods, slices made in routine way were used to observe the pathology changes.Results:1.mGluR2/3 were expressed in mice lung tissue.LPS treatment in vivo could effectively decrease the expression of mGluR3 mRNA in lung tissue of mouse.2. LPS injection could effectively increase the levels of glutamate, while decrease the levels of threonine, methionine and arginine in BALF, no significantly changes were observed in other amino acids.3. Protective role of IlmGluRs antagonist LY341495 on acute lung injury induced by LPS.Mice were treated with LY341495 (1mg/kg, ip.) 20 minutes before injection of LPS,①The ratios of wet-to-dry weight of lung were reduced to control level;②The activity of MPO,production of NO,activity of iNOS and production of MDA were depressed while the activity of SOD was elevated;③The inflammatory response in the lung was depressed.Conclusions:1. II mGluRs is distributed in the lung tissue cells.LPS could effectively decrease the expression of mGluR3 mRNA in lung tissue.2.Lung tissue cells have basic Glu secretion. The LPS in high dose stimulates the Glu release from lung, this means that lung tissue is one of important sources of Glu in LPS-induced ALI.3.Endogenous Glu involved in LPS-induced ALI via IImGluRs activation. II mGluRs antagonist LY341495 plays a protective role in LPS-induced ALI.