취효소 인자(lipase, phospholipase A 및 elastase)관류로 인한 적출 취장의 외분비 변동

Abstract

[영문]

[한글]

취조직의 염증 병변은 취효소 자체로 인하여 더욱 악화될 것이라는 견해는 이미 Klebs(

1868)에 의하여 시사되었고 그후 Chiari(1896)의 소화효소에 의한 취조직의 자가 소화 개

념이 주장되어 이 견해는 현재까지도 급성 취장염의 병태 생리학적 기전으로 인정되고 있

다. 자가 소화설은 단백분해 효소 및 지방분해 효소가 취조직내에서 활성화되며 이와같은

취효소의 활성화는 국소빈혈, 저산소증, 외상, 감염, 독소 등에 의해 일어난다고 믿고

있다.

활성화된 효소 특히 trypsin은 다른 불활성 효소를 활성화 시켜 취조직 및 취장 주위

조직의 소화를 유발하므로 세포막이 소화되고, 부종, 실질조직 출혈, 혈관손상, 혈액응고

장애, 지방괴사 및 실질조직 괴사가 나타난다. 더구나 trypsin, chymotrypsin, elastase

, phospholipase A, 혈장 kinin, histamine, 심근 억제인자(MDF)등 각증 독성물질이 염증

조직으로부터 유리된다. 이와같이 유리된 독성물질이 전신 순환에 유입될 경우 취장을 포

함한 여러 장기의 심한 기능장애를 초래한다. 김 등(1981)은 trypsin및 담즙산을 적출취

장에 관류하였을 경우 심한 취의분비 억제과 함께 취장으로부터 삼출액이 증가된다고 보

고하였다.

본 실험에서는 lipase, phospholipase A 또는 elastase등 취효소 병인자를 각각 고양이

적출취장표본에 관류시켜 이로 인한 취의분비 기능 변동을 검색하여 다음과 같은 결론을

얻었다.

1. 전해질 용액(Krebs-Ringer bicarbonate buffer)관류로 적출 고양이 취장표본은 6시

간 이상 일정한 취액분비와 효소분비 반응을 나타치고 조직 삼출액은 경미하게 나타났다.

2. Lipase 5 U/ml를 첨가한 전해질 용액을 관류하면 취액분비는 관류전 치의 반이하로

감소되고 효소분비는 현저하지는 않았으나 저하되었다.

3. Phospholipase A를 첨가 관류하면 취의분비 기능의 억제 경향을 나타내나 현저하지

는 않았다.

4. Elastase 첨가 관류로 인한 취의분비 기능 변동은 경미하였다.

5. 관류액에 첨가한 세 효소는 모두 조직 삼출액 양을 증가시켰으며 특히 elastase에서

현저하였다.

이상의 결과로 보아, 취장염에서는 조직에서 유리되어 혈액에 증가하는 취효소로 인하

여 취장 외분비 기능의 억제와 삼출액의 증가를 초래하며, 전자는 조직병변 발생의 병인

자가 되고, 후자는 shock발생의 주요 원인이 될 수 있다고 생각한다.

Influence of Pancreatic Enzyme Factors(lipase, phospholipase A and elagtase) on the

Exocrine Secretion in Isolated Cat Pancreas

Jong Ho Kim

Department of Medical Science The Graduate School, Yonsei University

(Directed by Professor Sa Suk Hong, M.D.)

No matter what the etiology of the acute pancreatic inflammation, the currently

favored mechanism underlying the initiation of pancreatitis is that of

autodigestion. As ealy as 1868, Klebs had attributed severe inflammatory changes to

"pancreatic ferments" that were produced by the gland, and subsequently Chiari

(1876) introduced the view that autodigestion throughdigestive enzymes is the main

cause of acute pancreatic necrosis.

The autodigestion theory proposes that pancreatic proteolytic and lipolytic

enzymes are activated within the pancreas proper and this activation of pancreatic

zymogens is believed to result from the effects of a variety of influences such as

ischemia, anoxia, trauma, infections, endotoxins and exotoxins. These activated

zymogens, especially trypsin, then activate other enzymes, which results in the

digestion of pancreatic and peripancreatic tissues. Thus cell membranes are

digested, and edema, interstitial hemorrhage, vascular damage, coagulation

necrosis, fat necrosis and parenchymal cell necrosis occur.

Moreover. potentially toxic substances, such as trypsin. chymotrypsin, elastase,

lipase, phospholipase A, plasma kinins, histamine and myocardial depressant factor,

are liberated from inflamed pancreas during an attack of acute pancreatitis leading

to vasodilatation, increased permeability and edema. When these substances are

carried to systemic circulation, a generalized toxemia mar result in profound

functional disturbances within different organ systems including pancreas itself.

It is reported that perfusion of trypsin and chenodeoxrcholic acid cause profound

inhibition of secretin induced pancreatic secretion with marked increase of exudate

from the organ in isolated cat pancreas.

In the present study, the effects of circulating lipase, phospholipase A and

elastase on the exocrine pancreatic functions as well as its relation on the

pathogenesis of acute pancreatitis were examined employing saline perfused isolated

cat pancreas.

Mongrel cat, of either sex weighing about 2 kg, was anesthetized with

secobarbital(45 mg/kg, ip), then pancreas was isolated and perfused with

Krebs-Ringer bicarbonate buffer at the rate of 6 ml/min.

Each enzyme to be tested was added to the perfusate. The optimal flow of

pancreatic juice was maintained by infusing submaximal dose of secretin and the

enzyme secretion was evoked by cholecystokinin octapeptide(CCK-OP).

The results are summarized as follows.

1. The isolated cat pancreas maintained constant secretory response to secretin

and CCK-OP for the duration of experiment when perfused with Krebs-Ringer

bicarbonate buffer. Furthermore, the changes in the volume of exudate from the

perfused organ, if any, were small and negligible.

2. Perfusion with lipase inhibited both the secretin.induoed pancreatic flow and

the CCK-OP evoked secretion of pancreatic ensymes. While the reduction in the

pancreatic flow was marked and dependent on the dose of lipase infused, the

decrease in the secretion of pancreatic enzymes was less marked and was not dose

dependent.

3. Perfusion with phospholipase A produced moderate inhibitions both in the flow

of pancreatic juice and the secretion of pancreatic enzymes.

4. Perfusion with elastase, even at high doses, had little effect on the exocrine

funotions of pancreas.

5. All three enzymes perfused had increased the leakage of exudate from pancreas

in an irreversible manner. Among them, the influence of elastase was most

remarkable.

These results suggest that increase of release of these potentially toxic

substances from the inflamed pancreas may not only produce an inhibitory effect on

the exocrine function of pancreas itself, but also contribute to the development of

shock by increasing leakage of exuadate during acute pancreatitis.