[Pathophysiological study on the mucosal defense system of genetically obese Zucker rats].
Avainsanat
Abstrakti
The obese Zucker rat is an animal model of genetically inherited obesity demonstrating remarkable hyperphagia. In the present study, to try to clarify the relationship between obesity and gastric function including gastric mucosal integrity, the gastric acid secretion, emptying, and mucosal resistance against ulcerogenic agents were compared in lean and obese Zucker rats. Male lean and obese Zucker rats were housed at 25 degrees C under 12-hr/12-hr lighting cycle (on at 7:00 AM). The gastric acid output of obese Zucker rats was markedly smaller than that of lean Zucker rats, whereas there was no significant difference in gastric emptying in both groups. The degree of mucosal lesion formation induced by ulcerogenic agents was assessed by measuring the total length of all mucosal lesions observed (ulcer index; mm). The intragastric administration of indomethacin (20 mg/kg) produced hemorrhagic mucosal lesions in both lean and obese groups of Zucker rats, but the ulcer index was remarkably smaller in obese Zucker rats than that of their lean littermates (5.2 +/- 1.2 mm vs. 17.5 +/- 3.5 mm, mean +/- SEM, P < 0.01). In addition obese Zucker rats exhibited stronger resistance against the intragastric challenge of absolute ethanol (1 ml/rat), a necrotizing agent, with its ulcer index being 8.5 +/- 2.7 mm, compared with lean Zucker rats whose ulcer index was 26.4 +/- 5.4 mm (P < 0.01). The bilateral subdiaphragmatic vagotomy decreased both gastric acid secretion and the ulcer index of indomethacin-induced gastric injury observed in both obese and lean Zucker rats, whereas there was no significant difference in the ulcer index of ethanol-induced gastric injury. These results suggest that obese Zucker rats exhibit enhanced resistance against ulcerogens and decreased acid output. It is also speculated that the vagal system might be involved in inhibition of acid secretion and formation of indomethacin ulcers in obese Zucker rats.