Nakano H, Monden M, Umeshita K, Murata M, Miyoshi H, Kanai T, Gotoh M, Mori T
Department of Surgery II, Osaka University Medical School, Japan.
Surgery. 1994 Nov;116(5):883-9.
Prostaglandin I2 (PGI2) analogues have been suggested to protect the liver from ischemia-reperfusion injury, but the exact mechanism remains to be proved.
Primary cultured rat hepatocytes were exposed to superoxide generated by mixing hypoxanthine and xanthine oxidase, and changes in cell viability, cytosolic free calcium concentration ([Ca2+]i), and adenosine 3',5'-cyclic monophosphate (cAMP) concentration were assessed. The PGI2 analogue (OP2507 or OP41483) at 1 to 100 ng/ml was given as treatment.
PGI2 analogues suppressed hepatocyte death in a dose-dependent manner (p < 0.01; OP2507 at 10 and 100 ng/ml, OP41483 at 100 ng/ml). At the end of 1-hour preincubation with OP2507, a significant rise in cAMP concentration was observed. Moreover, addition of dibutyryl cAMP suppressed hepatocyte death. A rise in [Ca2+]i, which preceded cell death, was prevented by PGI2 analogues or dibutyryl cAMP.
The increase in cellular cAMP followed by suppression of [Ca2+]i elevation might be the major cause of the cytoprotective effect of PGI2 analogues in superoxide-induced hepatocyte injury.
前列腺素I2（PGI2）类似物被认为可保护肝脏免受缺血再灌注损伤，但其确切机制仍有待证实。
将原代培养的大鼠肝细胞暴露于由次黄嘌呤和黄嘌呤氧化酶混合产生的超氧化物中，评估细胞活力、胞质游离钙浓度（[Ca2+]i）和环磷酸腺苷（cAMP）浓度的变化。给予1至100 ng/ml的PGI2类似物（OP2507或OP41483）进行处理。
PGI2类似物以剂量依赖性方式抑制肝细胞死亡（p < 0.01；10和100 ng/ml的OP2507，100 ng/ml的OP41483）。在用OP2507预孵育1小时结束时，观察到cAMP浓度显著升高。此外，添加二丁酰cAMP可抑制肝细胞死亡。PGI2类似物或二丁酰cAMP可防止细胞死亡前出现的[Ca2+]i升高。
细胞内cAMP增加随后抑制[Ca2+]i升高可能是PGI2类似物在超氧化物诱导的肝细胞损伤中发挥细胞保护作用的主要原因。
