Prostaglandin E₁の肝細胞障害防御作用に関する実験的研究 ： ラット初代培養肝細胞を用いたD-galactosamine惹起性肝細胞障害モデルによる検討

Abstract

The cytoprotective effect of prostaglandin E₁ (PGE₁) on the D-galactosamine (GalN)-induced injury of rat hepatocytes in primary culture was investigated. The LDH release from the GalN (1 mg/ml)-treated hepatocytes was suppressed in the presence of PGE₁ (10⁻⁶ and 10⁻⁵ M). PGE₁ (10⁻⁷ and 10⁻⁶ M) had a tendency to inhibit the reduction of albumin secretion in the GalN-treated hepatocytes. The decreases of intracellular phospholipids and cholesterol in the GalN-treated hepatocytes were completely restored in the presence of PGE₁ (10⁻⁵ M). Though fatty acid composition in the GalN-treated hepatocytes showed an increase in linoleic acid level, and decreases in oleic acid and palmitoleic acid levels, these decreases were not affected by PGE₁ addition. PGE₁(10⁻⁶ and 10⁻⁵ M) raised cyclic AMP (cAMP) release from the GalN-treated hepatocytes. Dibutyryl cAMP also depressed LDH release from the GalN-treated hepatocytes. After a two-hour treatment with GalN (1 or 10 mg/ml), hepatocytes showed an enhanced specific binding to [³H]PGE₁. Scatchard plot analysis indicated that GalN treatment increased the number of the binding sites to [³H]PGE₁. It is confirmed in the present study that PGE₁ has cytoprotective effects on experimental hepatocellular injury. Also, it is suggested that these cytoprotective effects of PGE₁ could be at least in part associated with the cAMP-dependent mechanism enhanced probably by the increase of specific PGE₁ receptors in the early stage of hepatocellular injury.