ラット胃潰瘍における各種抗潰瘍薬の作用機序に関する実験的研究

抄録

In order to evaluate the anti-ulcer drugs, their effects against the ulcer formation were studied in rats. The ulcers were experimentally produced by 18 hour-ligation of the pyrolus after 48 hour-fasting (Shay ulcer) and by 20 hour-confinement of the rat in the water immersed cage after 24 hour-fasting (stress ulcer). The rats were treated by anti-ulcer drugs promptly after above mentioned procedure.
The stomach so obtained were carefully studied with references to the severity of the ulcer formation, the amount of the gastric jouce, its total acidity and pepsin activity, being compared to the controled stomach which were obtained from the rats without any pre-treatment. The severity of the ulcer formation were scored to obtain ulcer index according to number and size of the ulcer formed and nature of the gastric mucosa and the perforation of the wall. Pepsin activity was determined according to Bonfils' method with auther's own modification. Addition of Folin and Ciocalteu's Phenol agent to the sample at the last step of Bonfils' original procedure was proved to improved the accuracy and sensitivity of its measurement.
1) Human placental extract was administered intraperitoneally with a dose of 100,200,300,400 and 500mg before the ulcer experiment. In Shay ulcer experiment, the extract was most effective with a dose of 400mg and of 200mg, with regards to the anti-ulcer and anti-pepsin actions, respectively. The rat group pretreated by the extract showed significantly lower ulcer index, smaller gastric secretory volume, lower pepsin activity level as compared to the control group (P<0.01). In stress ulcer experiment, the extract was proved to be effective with regard to ulcer index.
2) Urogastrone was administered intravenously with a dose of 0.1 to 2. Omg. The drug revealed its most prominent anti-ulcer action with a dose of 0.3mg while its anti-pepsin action was not observed at any dose levels. The group pretreated by urogastrone showed lower ulcer index, higher pH level of the gastric jouce than the control (p<0.01). In stress ulcer experiment, anti-ulcer action of urogastrone revealed a dose-dependency and reached its maximum at a O.5mg dose level. The group pretreted by this drug showed significantly lower ulcer index than the control group (p<0.01).
3) Basic alminum sucrose sulfate was administered by a dose of 200,300,400, or 500mg in stress ulcer experiment and 5,10,15,25,50, or 100mg in Shay ulcer experiment.
In Shay ulcer experiment, the drug revealed 100% anti-ulcer action at the dose level of 25mg or more. Its anti-pepsin action showed a dose-dependency. The group pretreated by this drug showed significantly lower ulcer index, pepsin activity total acidity and higher pH as compared to the control (p<0.01). In stress ulcer experiment, this drug showed its maximum effect against ulcer formation with a dose level of 300mg.
4) Secretin was administered intraperitoneally with a dose of 1.0 to 7.0 units. In Shay ulcer experiment, anti-ulcer and anti-pepsin action of this drug were proved to be most powerful with a dose of 1 unit and of 7 units, respectively. Dose-dependency of these effects, however, was not clearly observed. The rat group pretreated by secretin revealed significantly lower pepsin activity level (p<0.01) and lower ulcer index (p<0.05) as compared to the control group, in Shay ulcer and stress ulcer experiments, respectively.
5) Among the four anti-ulcer drugs used in this study, basic alminum sucrose sulfate was proved to be most effective against ulcer formation as well as acidity and pepsin activity of the gastric jouce in the rat ulcer experiments.