The Regulation Of MCP-1 MRNA Expression In Rat Model Of Phlmonary Fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis(IPF) disease is difficult to treat generally which makes many clinical doctors puzzled. The pathological mechanism of IPF disease has not been clarified elabrately, and there are not effective ways to cure it. Recently, a new and potent monocyte chemoattractant, MCP-l has been identified. A large number of experiments demonstrated that MCP-l could play an important role in organism defense, antiinflammation and anticancer by chemoattracting and activating monocyte specially, futhermore, MCP- 1 is chemotactic to lymphocyte. Because of its high relation with inflammatory diseases and autoimmune diseases, MCP-l will have a prospect of becoming an ideal candiadate of molecular target for the new drug. However, the action mechanism of MCP-l has not been defined clearly yet, we do not know whether the expressions of MCP-1 in various tissues have stimuli-inducing difference which may reflect that the imflammtory diseases will occur in varying degrees and in differential tissues or organs, this issue has become one of the focus in the world, and the research about regulation of MCP-1 expression in rat model of bleomycin- induced pulmonary fibrosis, has not been reported up to now. OBJECTION: To study the expressions of MCP-1mRNA by lung tissues within rats of bleomycin-induced pulmonary fibrosis and the regulation of their exprssions in reponse to LPS, CVP and Dex, and supply substantially the thoretical imformations for curing IPF desease. METHODS: (DAfter treating i.p. at different time(Oh, 4h, 6h, 8h) with LPS, BLM, IFN- y and TNF- a, we examed the expression of MCP-l mRNA in various tissues(liver, lung, kidney, heart, skin, spinal cord, small intestine) by means of quantitative RT-PCR. fter intratracheal instillation of BLM, the histopathological changes of lung injury were observed and the kinetics of expression of MCP- 1 mRNA were shown by quantitative RT- PCR at day 0, 6h, day 1, day 3, day 7. ㏕he rats of BLM-induced lung injury (at day 3) were treated i.p. with LPS, Dex and CVP, the accumulations of monocyte were evaluated and counted in optical microscopy field, the regulatory effects of various treatments on MCP-1 mRNA expression were detected by the means of quantitative RT-PCR respectively. RESULTS: @MCP-1 mRNA was induced by LPS strongly in liver and lung, moderately in kidney, but negatively in spinal cord, heart, skin and small intestine. ㏕he time course of MCP-1 mRNA expression in liver and lung was as follows: maximal expression appeared in 4 hours after treating i.p. with LPS and thereafter it declined rapidly, but the level of expression was still much higher at 8 hours than those at 0 hour. LM, IFN- y and TNF- a had similar effects, but the less extent of inducing the expression of MCP-l mRNA was obtained. (DThe intratracheal instillation of bleomycin for 1 to 3 days, the lung tissues showed earlier typical symptoms such as accumulating of inflammatory cell, thickening of alveolar wall, hemorrhages, or edema et a!. Seven days later, pulmonary fibrosis occurred slowly. The time course of MCP-l mRNA expression in lung injury tissues showed: 6 hours shortly after instillation, the expression of MCP-l mRNA began to increase, reached the peak at the third day, and declined thereafter. ㏕he level of expression of MCP-l mRNA in injuried lung at day 3 (control) was much higher than those in the sham-operation groups(2.47 .38 vs 1.30 0.25 respectively, P<0.0 1), but much lower than those in the LPS-treated gro...