| Semicarbazide-sensitive amine oxidases (SSAO) are a group of copper, quinone andhistidine residue containing amine oxidases which catalyze oxidative deamination reaction ofamine compounds and are sensitive to semicarbazide. Its physiological and pathological functionremains unclear. In human, SSAO is present either as soluble or as membrane forms located incirculation and many tissues and organs, especially in adipocytes, vascular endothelial andsmooth muscle cells. It has been found that SSAO activity changes in some pathologicalconditions. For example, in the acute peritonitis, chronic dermatitis or pneumonia conditions,SSAO activity increased in diseased region. In addition, plasma SSAO activity increased inhepatocirrhosis patients. Interestingly, the protein expression and activity of SSAO were reportedunchanged in acute lung inflammation, which are different from our expectations. In the presentstudy, we chose suitable animal model for investigation of the variation of SSAO activity in theacute lung inflammation, and the regulation mechanism of SSAO.Main procedures and methods1. Established Wistar, SD rats, New Zealand rabbit model of acute pneumonia, selected andoptimizated animal models for SSAO activity study.2. Evaluated the quality of the rabbit model of acute lung inflammation by animalsymptoms observation, WBC and pathological section.3. After treated with different administration ways and doses of LPS, plasma SSAOactivities were compared.4. Detected the variation of plasma SSAO activity after LPS treatment.5. Purified plasma for the endogenous substances.Results:1. The experiment proved that administration by ip or iv induced more side effects thanintratracheal administration. Rats plasma SSAO activity is too low, so rabbit model wasmore ideal than rats. The direct administration by tracheal intubation is better thantraditional tracheotomy intubation administration in some aspects such as less sideeffects, shorter operating hours, avoiding the inflammation caused by tracheotomy. Butthe modeling method may cause uneven distribution of drug in the lung tissue.2. The New Zealand rabbit were directly administrated with different doses of LPS (1.0mg·kg-1,1.5 mg·kg-1,2.0 mg·kg-1,3.0 mg·kg-1) through tracheal intubation. After treatment with 2.0 mg·kg-1 LPS, the variation of SSAO activity fluctuated larger thanthat of other doses. Therefore, we chose 2.0 mg·kg-1 LPS for rabbit model of acute lunginjury.3. After the treatment, rabbit blood SSAO activity fluctuated regularly. The SSAO activityincreased to the maximum at 16 h and then decreased to the minimum at 48 h, and thengradually returned to normal. Compared with the 0 hour before treatment, the maximumincrease was up to 23.33±9.63％(P＜0.05), and the maximum decrease was up to17.83±8.69％(P＜0.01).4. The extracts obtained from plasma denatured by 70℃water bath could inhibit SSAOactivity in fresh rabbit plasma. SSAO activity in normal plasma was decreased 9.05％by normal plasma extracts, and decreased 21.15％by low acitivity plasma extractsobtained from inflammation model at 48 h after treatment with LPS. The endogenousinhibitor in denatured plasma needs further purified for its impurities.Conelusions:1．Direct administration Of New Zealand rabbit by tracheal intubatiOn rather thantracheotomy or other administration methods, could get a stable model with less sideeffects. Rabbit plasma SSAO activity is high, and the New Zealand rabbit is moresuitable for continuous blood collection. So, rabbit is an ideal animal used to study thenature of SSAO.2. The best dose of New Zealand rabbit model of acute lung inflammation is 2.0 mg·kg-1LPS by endotracheal intubation.3. New Zealand rabbit plasma SSAO activity changed regularly, suggesting that SSAOplay a role in acute lung inflammation.4. Endogenous SSAO inhibitors may exist in the plasma of LPS-inducible acute lunginflammation.
|
PDF Full Text Request