Sone H, Okuda Y, Kawakami Y, Yamashita K
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Tsukuba, Japan.
Life Sci. 1996;58(3):239-43. doi: 10.1016/0024-3205(95)02281-3.
To clarify the involvement of the prostaglandin (PG)-thromboxane (TX) system in diabetic retinopathy, the production of thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and prostaglandin E2 (PGE2) and the effects of a thromboxane synthase inhibitor (TXSI; KDI-792; 5Z-6[(2S,4R)-4-(4-chlorophenylsulfonylamino)-1-(3-pyridyl methyl)-2 pyrrolidinyl]-5-hexenoic acid hydrochloride) were examined under high glucose concentration using bovine retinal endothelial cells. TXB2 was used as an index of TXA2, and 6-keto-PGF1 alpha as an index of PGI2. The levels of TXA2 and PGI2 were 182.3 +/- 34.3 pg/mg and 336.7 +/- 36.1 pg/mg protein at 5.5 mM of glucose, and both increased linearly with the glucose concentration to reach 430.1 +/_ 29.7 pg/mg and 511.4 +/- 65.8 pg/mg protein at 33 mM glucose (mean +/- SD, P<0.01). Neither TXA2 nor PGI2 changed significantly under elevated osmolarity. The production of PGE2 was affected only slightly by high glucose concentrations or by TXSI. Normalization of the PGI2/TXA2 ratio by TXSI at high glucose concentrations was marked.
为阐明前列腺素（PG）-血栓素（TX）系统在糖尿病视网膜病变中的作用，在高糖浓度条件下，使用牛视网膜内皮细胞检测了血栓素A2（TXA2）、前列腺素I2（PGI2）和前列腺素E2（PGE2）的生成情况以及血栓素合酶抑制剂（TXSI；KDI-792；5Z-6[(2S,4R)-4-(4-氯苯基磺酰氨基)-1-(3-吡啶基甲基)-2-吡咯烷基]-5-己烯酸盐酸盐）的作用。TXB2用作TXA2的指标，6-酮-PGF1α用作PGI2的指标。在葡萄糖浓度为5.5 mM时，TXA2和PGI2的水平分别为182.3±34.3 pg/mg蛋白和336.7±36.1 pg/mg蛋白，两者均随葡萄糖浓度呈线性增加，在葡萄糖浓度为33 mM时分别达到430.1±29.7 pg/mg和511.4±65.8 pg/mg蛋白（平均值±标准差，P<0.01）。在渗透压升高的情况下，TXA2和PGI2均无显著变化。高糖浓度或TXSI对PGE2的生成影响较小。在高糖浓度下，TXSI使PGI2/TXA2比值显著恢复正常。
