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납(Lead)이 취 외분비 기능에 미치는 영향

Title
납(Lead)이 취 외분비 기능에 미치는 영향
Other Titles
Effect of lead acetate on pancreatico-biliary secretion
Authors
신윤용
Issue Date
1981
Department/Major
대학원 약학과
Publisher
이화여자대학교 대학원
Degree
Master
Advisors
김원준
Abstract
납이 빈혈의 원인이 된다고 알려진 이후 유해 중금속인 납이 생물체에 미치는 영향을 관찰하기 시작했다. 납은 주로 소장을 통하여 흡수되고 뇨중으로 배설된다. Hamilton(1978)은 발육부진이나 빈혈과 같은 납의 독성이 철 결핍시 쉽게 나타나며, 철 공급에 의해 억제되는 사실로부터 납은 소장에서 흡수 과정중 소장 점막 단백질에 있는 같은 결합 부위에서 철과 서로 경쟁함을 밝혔다. 납은 phosphatase, 단백질의 cysteinyl, histidyl 잔기, purines, pterines, porphins등과 같은 ligands에 강력한 친화력을 갖고 있어 기능적인 sulfhydryl group을 갖고 있는 많은 효소들을 불화성화 시킨다. 납은 hemoproteins와 cytochrome 생합성의 구성 효소인 δ-ALA dehydratese를 억압함으로써 빈혈을 유발하고 drug metabolism에 영향을 미치며, 또한 renal Na^(+)-K^(+) 의존성 ATPase를 억압하여 natriuresis등 독성을 나타낸다. 납은 소장점막이 표적장기이고, 여러 효소를 억제시킨다는 보고는 있으나 소화기에 대한 영향은 밝혀진 바 없다. 본 실험에서는 납이 취장 외분비 기능에 미치는 영향을 검색할 목적으로 쥐를 사용하여 납 단독투여, 납과 EDTA 병용투여, 납과 FeSO_(4) 병용 투여시 담취의 분비 기능을 관찰하여 다음과 같은 결과를 얻었다. 1. 대량 단회 투여군에서 현저한 amylase 배출량 감소를 볼 수 있었다. 2. 납을 1, 2, 3주간 투여한 군에서 체중 증가율이 감소하였고 1주에서 EDTA, FeSO_(4)는 이를 회복시켰다. 3. 담취액 분비량은 납을 1, 2, 3주 투여했을 때 감소하였고, EDTA, FeSO_(4)를 3주간 병융 투여했을 때 회복되었다. 4. Bilirubin 배출량은 납을 2주, 3주간 투여시 증가하였으며 EDTA나 FeSO_(4) 병용투여가 별 변동을 나타내지 않았다. 5. Cholate와 lipase 배출량은 모든 실험군에서 변동이 없었다. 6. Amylase 배출량은 1, 2, 3주간 납을 투여했을 때 현저히 감소하였고 EDTA나 FeSO_(4) 병용 투여로 변동을 볼 수 없었다. 7. 납을 처치한 쥐로부터 적출 취장에서 amylase 분비량은 1, 2, 3주에 걸쳐 현저히 감소되었다. 8. 납처치에 위한 취장 acina cell의 공포변성을 관찰하였다. 이상의 결과로 납은 소화기계 억제 작용이 있는 것으로 사료된다.;No evidence has accumulated that Lead compound is an essential component for biological function in animals. Lead is absorbed primarily through the epithelial mucosal cells in duodenum and the absorption can be enhanced by the substances which bind Lead and increase its solubility. Iron, zinc and calcium ions, however, decrease the absorption of lead without affecting its solubility, probably by competing for shared absorptive receptors in the intestinal mucosa. Therefore, the absorption of lead is increased in iron deficient animals. Lead shows a strong affinity for ligands such as phosphate, cysteinyl and histidyl side chains of proteins, pterins and porphyrins. Hence Lead can act on various active sites of enzymes, inhibiting the enzymes which has functional sulfhydryl groups. Lead inhibits the activity of δ-aminolevulinic acid dehydratase for the biosynthesis of hemoproteins and cytochrome, which catalyzed the synthesis of monopyrrole prophobilinogen from δ-aminolevulinic acid. Accordingly lead decrease hepatic cytochrome p-450 content, resulting an inhibition of the activity of demethylase an4 hydroxylase in liver. Little informations are available on the effect of lead on digestive system although the catastrophic effects of lead intoxication are well documented. The present study was, therefore, attempted to investigate the effect of lead on pancreatico-biliary secretion in rats. Albino rats of both seres weighing 170-230g were used for this study. The animals were divided into one control and three treated groups, i.e., control (physiologic saline 1.5ml/kg i.p.), lead acetate (10μmole/kg/day i.p.), Pb(Ac)_(2) and EDTA (each 10μ mole/kg/ day i.p.), Pb(Ac)_(2) and FeSO_(4)(each 10μ mole/kg/day i.p.). The pancreatico-biliarf juice was collected under urethane anethesia, and activities of amylase and lipase were determined by employing Surner's and Cherry and Crandall's methods. The summarized results are follows. 1. In the experiment for acute toxicity of Lead acetate, 20% of mortality was observed in rat treated with lead acetate as well as inhibition of the activity of amylase in the juice at the 3rd day of the treatment. 2. No increases in body weight were observed in rats treated with Lead acetate, while in control group the significant increases were observed. However, the body weights of animals were increased in the group lead acetate plus EDTA or FeSO_(4). 3. Lead acetate decreased significantly the volume of pancreaticobiliary juice whereas additional treatment of EDTA and FeSO_(4) prevented it. 4. Total actiuity of amylase was markedly reduced due to lead acetate treatment, but no change was showed following additional treatment with EBTA a.Id FeSO_(4). 5. No changes in the cholate and lipase output were observed in rats treated with lead acetate as compared with that of control rats. 6. Increase in bilirubin output in rats treated with lead acetate was shown on the 2nd and 3rd weeks treatment. 7. In the case of in vitro experiment, lead acetate also markedly inhibited release of amylase from pancreatic fragment. 8. Histologic finding indicated that acini vacuolation was induced in the pancreatic tissue of rat treated with lead acetate. From the above results, it might be concluded that lead acetate decreases the volume of pancreatico-biliary secretion and inhibits the amylase activity, by acting directly on pancreatic cells.
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