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Regulative Functions Of Lipopolysaccharide On Bronchi Inflammation Of Infant Asthma Rat Through Toll-like Receptor 4

Posted on:2010-08-01Degree:MasterType:Thesis
Country:ChinaCandidate:L MaFull Text:PDF
GTID:2144360278950032Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
ObjectiveToll-like receptor is one of the most important innate immunity pattern recognition receptors. Otherwise, eosinophilic (EOS) airway inflammation is one of the basic characteristics of allergic asthma. The present study aimed at understanding the effect of lipopolysaccharide (LPS) on change of TLR4 and EOS apoptosis on bronchi inflammation.MethodsFifty Sprague-Dawley (SD) rats (age 4 to 6 weeks, body weight 130 to 150 gram) were randomly divided into the control group(group A), asthma group(group B), dexamethasone group (DXM) (group C),high dose of LPS group (group D1)and low dose of LPS group(group D2) with 10 in each. Asthma model rats were sensitized with the mixture of ovalbumin (OVA, 1mg) and Al(OH) 3, 100 mg on day 1 and day 8, repeatedly exposed to aerosolized OVA after day 15,once a day for three days and continued for 30 minutes at every time. During the sensitization stage and challenge stage, 100μg/ml DXM were prepared with DXM group 1 hour before be sensitized and challenged. 0.1μg/ml and 100μg/ml LPS were prepared with high dose of LPS group and low dose of LPS group every other day during the sensitization stage and the same doses LPS 1 hour before be challenged on the stage of challenge. Use light microscope(LM) to observe the pathology changes of lung tissue and the Inflammationary cells count in BALF, Enzyme-linked immunoassay(ELISA), Situ hybridization and TUNEL to detect the levels of OVA-sIgE in serum , TLR4 mRNA and the percentages of apoptotic EOS.Results(1) Light microscope (LM) showed many inflammatory cells infiltration around the bronchi and blood vessels, bronchus mucus increased in asthma group and low dose of LPS group, whereas DXM group and the high dose of LPSgroup showed significantly milder changes.(2) Inflammationary cells count of asthma group in bronchoalveolar lavage fluid (BALF) showed that the total cell count, EOS absolute count and EOS % were higher than those of the control group (p<0.01), Those of DXM group and the high dose of LPS group is lower than asthma group (p<0.01), There were not significant differences between the low dose of LPS group and asthma group (p>0.05).(3) Level of OVA-sIgE in asthma group is higher than the control group (p<0.01), DXM group and high dose of LPS group is lower than asthma group (p<0.01), there were not significant differences between the low dose of LPS group and asthma group (p>0.05).(4) There were not significant differences in TLR4 mRNA detected by situ hybridization between asthma group and the control group (p>0.05), but it increased in DXM group, the low dose of LPS group and the high dose of LPS group (p<0.01)(.5)The percentages of apoptotic EOS in asthma group were lower than those in the control group (p<0.05), DXM group and the high dose of LPS were higher than those in asthma group (p<0.01), while there were not significant differences between the low dose of LPS group and asthma group (p>0.05).(6)TLR4 mRNA in the high dose of LPS group is higher than in the low dose of LPS group(p<0.01).ConclusionDXM and high dose of LPS can decrease OVA-sIgE lever, induce EOS apoptosis, Although low dose of LPS can activite the TLR4 signal transduction, it can not release asthma.
Keywords/Search Tags:Toll-like receptors, Asthma, Dexamethasone, LPS, Apoptotic
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