취장염 유발실험에서 알콜은 20%, 담즙산은 1% chenodeoxycholic acid, trypsin은 5000 BAEE u/ml을 각각 3ml씩 취관내로 주입한 후 취관을 3시간 동안 폐색하였다.
취장염에서의 취외분비기능은 취장염 유발 전후에 취액분비는 secretin 주사 또는 주입으로, 취효소분비 secretin 주입하에 cholecystokinin-octapeptide(CCK-OP) 자극으로 유발시켰다. 취외분비기능외에도 취효소 이동을 관찰하기 위하여 삼출액 및 정맥배출액 (venous drainage)으로 유출되는 amylase 활성을 Bernfeld법 (1955)으로 측정하여 IU/10min으로 표시하였다.
관류실험이 끝난 다음 일부 조직은 10% formalin에 고정하고 hematoxylin-eosin 염색하여 광학 현미경으로 관찰하였다.
실험성적을 요약하면 다음과 같다.
1. 적출 고양이 관류취장표본에서 취장염 유발인자라고 지목되는 담즙산, 알콜 및 trypsin을 취관내 주입 결찰하여 실험적 취장염을 유발시킬 수 있었다.
2. Secretin자극 취액분비치는 생리적 식염수 주입결찰군에서 별 변동이 없으나 알콜, trypsin 및 담즙산 주입결찰군에서는 그 순위로 감소현상이 심하였다.
3. CCK-OP자극 취효소 분비치는 생리적 식염수 주입결찰만으로도 현저히 저하되며 알콜 및 trypsin주입군은 생리적 식염수 주입군의 반응과 비슷하나 담즙산 주입군에서는 심히 억압되어 효소분비를 거의 볼 수 없었다.
4. 취장염 발생인자의 취관내 주입결찰로 급격한 정맥 배출액의 감소와 삼출액의 증가를 나타냈으며 그 정도는 담즙산 처치군이 가장 심하고 그 다음 trypsin, 알콜 순이었다.
5. 취장염 발생으로 삼출액내로 amylase의 유출은 현저하여 주입결찰 후 1∼30분에 최고치에 달하였고, 특히 담즙산군에서 격심하였으나 정맥배출액을 통한 취효소 유출은 경미하였다.
6. 취장조직의 병리조직소견으로는 생리적식염수 또는 알콜처치군에서는 별 병변이 없으나 trypsin 주입결찰군에서는 국소괴사를, chenic acid처치군은 광범위한 실질조직괴사 병변을 나타냈다.
이상 결과로 보아 적출취장에서도 담즙산, 알콜 및 trypsin의 관내 주입결찰로 취장염 발생을 관찰할 수 있고 취외분비기능은 취장염 발생 초기에 급격히 저하되며 취효소의 조직외 이동으로 삼출액내에 고농도 개재함을 알 수 있었다.
[영문]
The ease with which pancreatitis is produced in the experimental animal is fortunately not matched in man. Nevertheless, the experimental approach has provided some clues regarding the pathophysiology of pancreatitis in man. Most studies on the pathogenesis of acute pancreatitis undertaken so far have been centered on the effects of pathogenetic factors instilled into the pancreatic duct in vivo and only few experiments were done in isolated preparations of pancreas.
Attempt was made to induce experimental pancreatitis in the isolated perfused cat pancreas with special reference to the changes of the exocrine secretory functions as well as pancreatic enzyme movement into vein and exudate.
The pancreas was isolated and perfused with Krebs-Ringer bicarbonate buffer. Pancreatitis was induced by means of obstructing the pancreatic duct for 3 hours after instilling 3ml of 20% alcohol, trypsin (5000 BAEE u/ml) or 1% chenodeoxycholic acid(chenic acid) into the duct and saline was instilled as control experiment. Secretin was injected or infused to induce pancreatic juice secretion and CCK-octapeptide (5ng) was given to evoke enzyme secretion before and after induction of pancreatitis. The volume and amylase content of the venous drainage and exudate were determined in the course of the experiment and the histopatlologic examination was done at the end of perfusion.
The results are summarized as follows:
1. Experimental pancreatitis can be induced in isolated perfused cat pancreas by means of instilling pathogenetic factors such as alcohol, trypsin and bile acid into the pancreatic duct with obstruction.
2. Secretin-induced pancreatic flow was little affected by saline instillation but it was markedly reduced by ethanol, trypsin and chenic acid in increasing order.
3. Amylase secretion evoked with CCK-octapeptide was significantly decreased by ductal obstruction regardless of instilled factors, however, chenic acid instillation caused more marked and showed scanty secretion of amylase.
4. Venous drainage was sharply decreased in vice versa the exudate was increased in trypsin and chenic acid instilled pancreas.
5. Amylase appearance into venous drainage was negligible in all groups. However, amylase leakage into exudate was extensive after intraductal instillation of chenic acid, trypsin and ethanol in decreasing order in early period and peak value was at
10∼30 minutes.
6. Histopathologic finding of pancreas showed focal parenchymal necrosis by trypsin and diffuse necrosis by chenic acid instillation but saline or ethanol caused only edematous changes.
By these findings it can be concluded that the exocrine pancreatic functions are abruptly deteriorated in experimental pancreatitis induced by intraductal instillation of ethanol, trypsin and bile acid in vitro preparation, and the pancreatic enzymes leak profoundly into exudate and not into venous drainage.