Waldum H L, Kvetnoi I M, Sylte R, Schulze B, Martinsen T C, Sandvik A K
Department of Medicine, University Hospital of Trondheim, Norway.
J Mol Endocrinol. 1998 Feb;20(1):111-7. doi: 10.1677/jme.0.0200111.
The peroxisome proliferator ciprofibrate induces hypergastrinemia without inhibiting acid secretion. The present study was carried out to assess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrate with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radioimmunoassay method, G cell density by histomorphometry after immunostaining for G cells, and gastrin, somatostatin and histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrate (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P < 0.01) in male and female Fischer rats as well as in female Wistar rats. Simvastatin and lovastatin did not affect serum gastrin. Antral G cell density increased significantly in female Wistar rats (P < 0.05) and non-significantly in the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance in antral mucosa increased markedly and significantly (P < 0.01) after ciprofibrate treatment. The present study shows that the peroxisome proliferator ciprofibrate induces hypergastrinemia secondary to an increased storage and synthesis of antral gastrin. Since somatostatin mRNA abundance also increased, the present study suggests that ciprofibrate and possibly other peroxisome proliferators in sufficient concentrations have a stimulatory effect on endocrine cells.
过氧化物酶体增殖剂环丙贝特可引起高胃泌素血症，但不抑制胃酸分泌。本研究旨在评估环丙贝特对不同品系大鼠血清胃泌素和胃泌素（G）细胞的影响，并将环丙贝特的作用与其他作用机制不同的降脂药物（洛伐他汀和辛伐他汀）进行比较。采用放射免疫分析法测定血清胃泌素，对G细胞进行免疫染色后通过组织形态计量学测定G细胞密度，采用Northern印迹分析法测定胃泌素、生长抑素和组氨酸脱羧酶（HDC）mRNA丰度。环丙贝特（100mg/kg/天，持续三周）可使雄性和雌性Fischer大鼠以及雌性Wistar大鼠出现显著的高胃泌素血症（P<0.01）。辛伐他汀和洛伐他汀对血清胃泌素无影响。环丙贝特处理后，雌性Wistar大鼠胃窦G细胞密度显著增加（P<0.05），其他大鼠则无显著变化。环丙贝特处理后，胃窦黏膜中胃泌素和生长抑素mRNA丰度均显著增加（P<0.01）。本研究表明，过氧化物酶体增殖剂环丙贝特通过增加胃窦胃泌素的储存和合成导致高胃泌素血症。由于生长抑素mRNA丰度也增加，本研究提示，环丙贝特以及可能其他足够浓度的过氧化物酶体增殖剂对内分泌细胞有刺激作用。
