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췌장염치료(膵臟炎治療)에 사용되는 수종약물(數種藥物)이 백서췌(白鼠膵)효소생성에 미치는 영향

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 Effect of several drugs used for pancreatitis on enzyme production by rat pancreas 
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[영문]With disclosing in knowledge of the Pathologic Physiology of the acute pancreatitis and advancements of newer specific measures in the handling of the disturbances, the medical or conservative treatment has yielded more satisfactory results. This has become more so since Katsch (1939) advocated active but conservative treatment for pancreatitis and except a few surgical indications, symptomatic and supportive measures have generally been employed and more efforts have been directed towards elimination of pain, management of shock, replacement of body fluids and electrolytes, and prevention of secondary infections. At the same time several drugs or measures that will reduce the secretion of pancreatic juice and suppress the activation of pancreatic enzymes have eagerly been sought after. For the purpose of obtaining some basic data, we have given several drugs to groups of rats intraperitoneally for three weeks, and the resultant changes in the pancreatic enzyme production, changes in serum enzymes and histological changes have been studied. Methods and Materials White rats weighing 140 to 180g were placed in individual cages and kept on synthetic diet containing 8% casein; 6% corn oil; 4% salt mixture; 8% yeast and 74% sucrose. Twelve grams of the diet was given per rat per day. The rats were divides into 7 groups each containing 12 animals. Each group was given the following medicine once a day for three weeks intraperitoneally. 1) Control group: Except the basic low protein diet, no medication was given in this group. 2) Atropine group: Atropine sulfate 2.5 mg/kg daily. 3) Hexamethonium group: Hexamethonium chloride 1mg/kg daily. 4) Trasylol group: Trasylol (Bayer) 1,000 u/kg daily. 5) Acetazolamide group: Sodium acetazolamide (Sodium Diamox) 100mg/kg daily. 6) Cortisone group: Cortisone acetate 5mg/kg daily. 7) Procaine group: Procaine hydrochloride 5mg/kg daily. Extraction of pancreatic enzymes: Fol]owing 21 days of consecutive medication, feeding was withheld for 24 hours and the rats were sacrificed by exanguination and the blood was taken from the femoral artery. The pancreatic tissue was removed and this was treated by the method described by Grossman et at. (1947) for enzyme studies. Enzyme determinations: Amylase, lipase, GOT and GPT heve been measured in the serum, and in the pancreatic tissue extract powder, amylase, lipase and trypsin have been measured using the methods of Nelson (1944), Cherry & Crandall (1932) and Anson (1938) respectively. GOT and GPT have been determined by the procedure described in No. 505 Sigma Tech. Bulletin. Histological examination: Pancreatic tissue was removed from two to three rats of each experimental group and this was fixed in 10% formalin solute on and the paraffin sections were studied for histological changes. Results Rats have been fed a low protein diet, and several drugs that are supposed to have beneficial effect on pancreatitis have been administered to the rats intraperitoneally once daily for 21 days, and the resultant changes in serum enzymes, changes of pancreatic enzymes and histological changes of pancreas hare been observed. The results are as follows: A. Effect on the serum enzymes: Serum GOT and GPT somewhat increased in atropine group but little change has been observed in hexamethonium. Trasylol and acetazolamide groups when compared with control group. It is noteworthy that serum amylase has significantly increased in cortisone group and serum lipase somewhat increased in atropine group. It is found that except in cortisone and atropine groups, the long term administration of the drugs that we used in this experiment did not cause significant change in serum enzymes. B. Effect on the enzyme production of pancreas: After rats were fed low protein diet, we tried to determine their growth in terms of their body weight. The rats generally showed an inhibition of growth. There was not much difference between control and medication groups in this aspect of growth except cortisone and hexamethonium groups in which significant decrease of body weight and slight increase of body weight were observed respectively. Changes in pancreatic enzymes are as follows: In atropine and cortisone groups, the total volume of enzymes significantly increased in all amylase, lipase and trypsin when compared with that of control group, and especially the increase of lipase was marked in atropine group and also marked increase of lipase per 100mg of tissue extract powder was noted. Total enzymes in the pancreatic tissue reflected the increase of pancreatic weight. However, hexamethonium and procaine groups that showed some increase of pancreatic weight have shown about the same amount of enzymes as control group. It is noteworthy that there was increase of pancreatic weight even though there was marked decrease of body weight in cortisone group. C. Histological changes of pancreas: Pancreatic acini of procaine group resembled closely that of control group, but alt the other groups showed enlargement of pancreatic acini, cellular hypertrophy and increase of zymogen granules. In general, enlargement of pancreatic acini were more marked in cortisone and hexamethonium groups, and the cellular hypertrophy in atropine and acetazolamide groups. Conclusions 1. Several drugs used for pancreatitis have been given for 21 days to rats fed on low protein diet and the resultant changes in serum enzymes, changes of the pancreatic enzymes and histological changes have been studied. 2. Serum amylase markedly increased in cortisone group, and serum GOT and GPT increased but slightly in atropine group. 3. Pancreatic enzymes markedly increased in both groups of atropine or cortisone treated, and the increase rate of enzymes was even higher in atropine group than in cortisone group. 4. Pancreatic tissue weight increased in atropine, procaine, cortisone and hexamethonium groups. Despite the fact that decrease of body weight was more marked in cortisone group than in other medication groups, there was found a definite increase of pancreatic weight in cortisone group. 5. Enlargement of pancreatic acini and cellular hypertrophy were generally observed in the treated groups and this was more marked in atropine and cortisone groups. In summary, long term administration of drugs, clinically used for treatment of pancreatitis, to rats did not depress the production of pancreatic enzymes, but rather brought about an increase of them particularly in the animals treated with atropine or cortisone. This fact together with the histologic findings of enlarged acini may explain that the drugs used in this experiment are everting above results by virtue of the suppressive properties of the secretion as well as the enhancement of the enzyme synthesis per se in part. (Partly supported by grant No. 65-847, China Med. Board of New York)
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