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실험적 진폐증에서 투여약제에 따른 면역학적 병리학적 조직변화
윤임중,임현우,노영만,오상용,정장영,임영,김경아 가톨릭 대학 산업의학 쎈타 산업의학연구소 1993 韓國의 産業醫學 Vol.32 No.2
To access the effects of some drugs such as piperazine phosphare, azathioprine and allopurinol in the experimental pneumoconiosis, 263 rats weighted 240-320 gm was divided into the control and eight experimental groups. To each group, the turbid solution mixed free silica, talc and natural coal dust of 50 mg in 0.8 ml saline were instilled intratracheally. At the begining and 5th week of experiment, piperazine phosphate(8mg/week orally), aspirin(1.5mg/day intramuscularly), azathioprine(25mg/day orally) and allopurinol(1.5mg/day orally) were administered simultaneously, while the dust turbid solution was only given to the control group. For each group the change of body weight. dry right lung weight, cellularity including total cell, macrophage, lymphocyte and neurtrophil in bronchoalveolar lavage fluid, superoxide ion, hydroxyproline, leukotriene B₄, tumor necrotsis factor, prostaglandin E₂were examined, and observed the pathological chages in lung tissue. The results were as follow : 1. The larger amount of their instilled dust and the longer observation period, the severer pathological findings were found in the lung tissue of each experimental group. 2. The body and dry right lung wight was not significantly changed in the experimental groups compared with the control group. 3. The number of total cell in bronchoalveolar lavage fluid was markedly less in the experimental group than the control one, while no significant difference was found in the percent alveolar macrophages and lymphocytes in both groups. However, the percent of neutrophiles was usually lower than in the control group. 4. The amount of superoxide ion was frequently less in the experimental group compared with the control one. 5. The amount of hydroxyproline was significantly lower in the experimental group than in the control one. 6. The amount of leukotriene B₄was usually less in the drug administered group than in the control one. 7. The amount of tumor necrotic factor was also frequently lower in each experimental group than in the control one. 8. The amount of prostaglandin E₂was usually higher in each experimental group than in the control one.
윤임중,김경아,정장영,김지원,노영만 大韓産業醫學會 1994 대한직업환경의학회지 Vol.6 No.2
To evaluate the therapeutic effect of various drug combination in experimental pneumoconiosis, a total of 240 Spraque-Dawley was instilled intratracheally by 50mg free silica or coal dust with 0.8 ml normal saline. In the control group, it was intratracheally instilled only dust at once, while from 11th week experimental groups were administered drug. Experimental groups were divided into 8 groups according to drug combination such as group treated with piperazine and aspirin, piperazine and allopurinol, piperazine and azathioprine, aspirin and allopurinol, aspirin and azathioprine, allopurinol and azathioprine, solumedrol, and cyclophosphamide. The duration of treatment was 10 weeks. All animals were killed at 20th week after dust instillation. We observed body weight at 20th week after dust instillation, the dry lung weight of left lung, total and differential cell count in bronchoalveolar lavage(BAL) fluid. Leukotriene B₄, tumor necrosis factor, and superoxide anion production from alveolar macrophage, amount of hydroxyproline in left lung, and the histopathologic examination in the right lung stained with hematoxylin-eosin and Masson's trichrome. The results were as follows 1. The dry weight of the left lung in groups of treated with piperazine combined with aspirin and piperazine combined with azathioprine was significantly decreased compared to the control group in silica instilled group. 2. The total number of cells in BAL in all experimental groups of silica instilled group and of piperazine/azathioprine and aspirin/allopurinol of coal dust instilled group were significantly decreased compared to each control group. 3. In silica instilled group, the percentage of macrophage in experimental group tended to be increased in comparison with the control group but neutrophil tended to be decreased. Among experimental group, in the group treated with solumedrol and solumedrol/cyclophosphamide, the percentage and number of lymphocyte markedly increased compared to each control group. 4. The amounts of hydroxyproline in the group piperazine/allopurinol and piperazine/azathioprine of silica instilled group were markedly lower than in the control group. 5. The production of TNF from alveolar macrophage in experimental group tended to be decreased compared to each control group. 6. The pathologic score that quantified the pathologic finding in the right lung, in all experimental groups except the treated with regimen contained solumedrol of silica instilled group was significantly decreased compared to control group. In coal dust instilled group, the pathologic score of the group treated with piperazine and allopurinol, aspirin and azathioprine, and allopurinol and azathioprine was markedly lower than control group. 7. We analyzed the indices for alveolitis and fibrosis. The most effective drug combination was treated with piperazin combined with azathioprine and piperazine combined with allopurinol.