Hiraishi H, Terano A, Ota S, Ivey K J, Sugimoto T
J Lab Clin Med. 1986 Dec;108(6):608-15.
Whether cimetidine protects gastric mucosal cells independently of its antisecretory effect has been controversial. Some investigators postulate that, on the contrary, cimetidine decreases the integrity of gastric mucosa. Furthermore, whether cimetidine influences gastric prostaglandin (PG) synthesis is debated. Therefore, we investigated and compared with 16,16-dimethyl-PGE2 (dmPGE2) whether cimetidine protects cultured rat gastric mucosal cells from indomethacin, and tested whether cimetidine affects gastric PG production by these cells. Cell damage was assessed by chromium 51-release assay. Concentrations of indomethacin greater than 1 mmol/L caused cell damage and increased 51Cr release in a dose-dependent and time-dependent fashion. dmPGE2 significantly reduced indomethacin-induced increase of 51Cr release, whereas cimetidine at both nonantisecretory and antisecretory doses did not alter 51Cr release caused by indomethacin. The cultured cells released PGE2 and PGI2 in amounts of 215 +/-18 and 56 +/- 3 (mean +/- SEM) pg/10(5) cells in 1 hour, respectively. Nondamaging concentrations of indomethacin caused a dose-dependent inhibition of PG release from cultured cells with 50% inhibitory concentration at a dose of 10(-6) to 10(-7) mol/L. Cimetidine did not alter gastric PG production. In summary, exogenous PG protected gastric mucosal cells from indomethacin in vitro, but cimetidine did not. In conclusion, cimetidine, which fails to affect gastric PG production, does not directly influence the integrity of gastric mucosal cells.
西咪替丁是否独立于其抗分泌作用来保护胃黏膜细胞一直存在争议。一些研究者推测，恰恰相反，西咪替丁会降低胃黏膜的完整性。此外，西咪替丁是否影响胃前列腺素（PG）的合成也存在争议。因此，我们进行了研究，并将西咪替丁与16,16-二甲基前列腺素E2（dmPGE2）相比较，观察其是否能保护培养的大鼠胃黏膜细胞免受吲哚美辛的损伤，并检测西咪替丁是否会影响这些细胞的胃PG生成。通过铬51释放试验评估细胞损伤情况。吲哚美辛浓度大于1 mmol/L时会导致细胞损伤，并使51Cr释放呈剂量依赖性和时间依赖性增加。dmPGE2显著降低了吲哚美辛诱导的51Cr释放增加，而无论是非抗分泌剂量还是抗分泌剂量的西咪替丁均未改变吲哚美辛引起的51Cr释放。培养的细胞在1小时内分别释放215±18和56±3（平均值±标准误）pg/10(5)细胞的PGE2和PGI2。非损伤性浓度的吲哚美辛会导致培养细胞的PG释放呈剂量依赖性抑制，50%抑制浓度为10(-6)至10(-7) mol/L。西咪替丁未改变胃PG的生成。总之，外源性PG在体外可保护胃黏膜细胞免受吲哚美辛的损伤，但西咪替丁不能。综上所述，西咪替丁不影响胃PG的生成，也不直接影响胃黏膜细胞的完整性。
