Effects of azintamide on gastric emptying in proton pump inhibitor related low gastric acid environment / 中华消化杂志

ABSTRACT

Objective:To explore the effects and underlying mechanisms of azintamide on gastric emptying and gastrointestinal hormone secretion in proton pump inhibitor related low gastric acid environment.Methods:A total of 60 rats were selected and randomly divided into low gastric acid control group, low gastric acid model group, low gastric acid and azintamide intervention group, high gastric acid control group, high gastric acid model group and high gastric acid and azintamide intervention group by random number table, with 10 rats in each group. The rats of low gastric acid control group and high gastric acid control group were all treated with 0.9% sodium chloride solution. The rats of low gastric acid model group and high gastric acid model group were established by intraperitoneal injection of 20 mg/kg omeprazole once per day for seven days, and subcutaneous injection of 2 mg/kg penta gastrin once per day for three days, respectively. The rats of low gastric acid and azintamide intervention group and high gastric acid and azintamide intervention group were gavaged with azintamide 50 mg/kg once per day for three days on the basis of low gastric acid model group and high gastric acid model group, respectively. Only the rats in three low gastric acid groups were analyzed. At Day 0, 2nd, 4th, 6th and 8th after modeling, the body weight of rats were compared. After modeling, the weight of gastric contents and pH of gastric fluid was measured and compared, and the peripheral blood levels of pepsinogen A (PGA), gastrin and cholecystokinin (CCK) were detected by enzyme linked immunosorbent assay. One-way analysis of variance and Tukey′s honestly significant difference post-hoc test were used for statistical analysis.Results:The pH value of gastric fluid in low gastric acid model group and low gastric acid and azintamide intervention group were both higher than that in the low gastric acid control group (2.17±0.53, 2.03±0.69 vs. 1.32±0.17), and the differences were statistically significant ( P=0.026 and 0.041, respectively). While there was no significant difference in pH value between the low gastric acid model group and low gastric acid and azintamide intervention group ( P>0.05). On the Day 0, 2nd, 4th, 6th and 8th after modeling, the body weight of rats of low gastric acid control group, low gastric acid model group and low gastric acid and azintamide intervention group was (285.40±10.86), (283.40±6.38), (282.00±5.04) g; (287.10±10.73), (283.20±5.83), (284.00±5.72) g; (292.20±11.18), (281.90±6.23), (289.00±5.82) g; (296.40±11.12), (277.70±6.96), (292.00±6.82) g; (300.80±11.29), (274.30±8.84), (297.00±4.17) g, respectively. On the Day 6th and 8th after modeling, the body weight of rats of low gastric acid model group was lower than that of the low gastric acid control group; and the body weight of rats of low gastric acid and azintamide intervention group was higher than that of low gastric acid model group, and the differences were statistically significant (both P<0.01). On the Day 0, 2nd, 4th, 6th and 8th, there was no statistically significant difference in body weight of rats between low gastric acid and azintamide intervention group and low gastric acid control group ( P>0.05). On the Day 0, 2nd, 4th, there were no statistically significant differences in body weight of rats between low gastric acid and azintamide intervention group and low gastric acid model group, and between low gastric acid model group and low gastric acid control group (both P>0.05). The weight of gastric contents of low gastric acid model group was heavier than that of low gastric acid control group ((2.36±0.11) g vs. (1.85±0.20) g), the weight of gastric contents of low gastric acid and azintamide intervention group was lighter than that of low gastric acid model group ((1.87±0.42) g vs. (2.36±0.11) g), and the differences were statistically significant ( P=0.019 and 0.016, respectively), and there was no statistically significant difference in weight of gastric contents between the low gastric acid and azintamide intervention group and the low gastric acid control group ( P>0.05). The peripheral blood level of PGA of rats of low gastric acid model group was lower than that of low gastric acid control group ((551.80±190.00) ng/L vs. (857.00±164.80) ng/L), while the peripheral blood level of PGA of the low gastric acid and azintamide intervention group was higher than that of the low gastric acid model group ((799.90±97.80) ng/L vs. (551.80±190.00) ng/L), and the differences were statistically significant ( P=0.011 and 0.037, respectively). There was no significant difference in peripheral blood level of PGA between the low gastric acid control group and the low gastric acid and azintamide intervention group ( P>0.05). The peripheral blood level of gastrin of the low gastric acid model group was higher than that of the low gastric acid control group ((49.31±11.93) ng/L vs. (35.59±5.29) ng/L), and the CCK level of the low gastric acid model group was lower than that of low gastric acid control group ((10.26±5.32) ng/L vs. (25.55±11.62) ng/L), and the differences were statistically significant ( P=0.037 and 0.035, respectively). The peripheral blood level of gastrin of the low gastric acid and azintamide intervention group was lower than that of low gastric acid model group ((35.65±6.49) ng/L vs. (49.31±11.93) ng/L), the level of CCK of the low gastric acid and azintamide intervention group was higher than that of low gastric acid model group ((27.59±11.22) ng/L vs. (10.26±5.32) ng/L), and the differences were statistically significant ( P=0.048 and 0.021, respectively). There were no significant differences in CCK and gastrin between low gastric acid and azintamide intervention group and low gastric acid control group (both P>0.05). Conclusion:Azintamide regulates the levels of gastrointestinal hormones CCK and gastrin under the condition of low gastric acid and affects the expression of pepsinogen A, thereby promoting gastric emptying in a low gastric acid environment.