Axelrod L, Cornelius P
Prostaglandins. 1984 Sep;28(3):333-52. doi: 10.1016/0090-6980(84)90021-2.
We studied the effects of two structurally unrelated inhibitors of the fatty acid cyclooxygenase and of alpha and beta adrenergic blockade on the elevated plasma levels of 13,14-dihydro-15-keto-prostaglandin (PG)E2, 6-keto-PGF1 alpha and thromboxane (TX)B2, the stable derivatives of PGE2, PGI2 (prostacyclin) and TXA2, respectively, in rats with streptozotocin-induced diabetic ketoacidosis (DKA). Meclofenamic acid and indomethacin each produced a significant decrease in the elevated plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1 alpha and TXB2. Phentolamine significantly reduced the plasma level of TXB2 but had no effect on the elevated circulating levels of glucose, free fatty acids, total ketones, 13,14-dihydro-15-keto-PGE2 or 6-keto-PGF1 alpha. Propranolol significantly reduced the elevated circulating levels of glucose, free fatty acids and total ketones but had no effect on the levels of the three prostaglandin derivatives. The ability of meclofenamic acid and indomethacin to reduce the plasma levels of 13,14-dihydro-15-keto-PGE2, 6-keto-PGF1 alpha and TXB2 confirms that the plasma levels of these three derivatives are elevated in rats with DKA. Since abnormalities in the production of PGI2 and perhaps other cyclooxygenase derivatives may contribute to the pathogenesis of certain important hemodynamic and gastrointestinal features of DKA, cyclooxygenase inhibitors may play a role in the management of selected patients with this disorder. Alpha adrenergic activity is essential for the maintenance of the elevated plasma TXB2 level in rats with DKA. The fall in the plasma TXB2 level during alpha adrenergic blockade appears to reflect inhibition of platelet aggregation and platelet TXA2 production, but other sources of the elevated plasma TXB2 level in DKA are not excluded. Beta adrenergic activity contributes to the maintenance of elevated circulating levels of glucose, free fatty acids and total ketones in experimental DKA but not to the elevated plasma levels of the prostaglandin derivatives.
我们研究了两种结构不相关的脂肪酸环氧化酶抑制剂以及α和β肾上腺素能阻滞剂对链脲佐菌素诱导的糖尿病酮症酸中毒（DKA）大鼠血浆中13,14-二氢-15-酮-前列腺素（PG）E2、6-酮-PGF1α和血栓素（TX）B2水平升高的影响，这三种物质分别是PGE2、前列环素（PGI2）和血栓素A2（TXA2）的稳定衍生物。甲氯芬那酸和吲哚美辛均可使升高的血浆中13,14-二氢-15-酮-PGE2、6-酮-PGF1α和TXB2水平显著降低。酚妥拉明可显著降低血浆TXB2水平，但对升高的循环血糖、游离脂肪酸、总酮体、13,14-二氢-15-酮-PGE2或6-酮-PGF1α水平无影响。普萘洛尔可显著降低升高的循环血糖、游离脂肪酸和总酮体水平，但对三种前列腺素衍生物水平无影响。甲氯芬那酸和吲哚美辛降低血浆中13,14-二氢-15-酮-PGE2、6-酮-PGF1α和TXB2水平的能力证实，DKA大鼠血浆中这三种衍生物水平升高。由于PGI2及可能其他环氧化酶衍生物生成异常可能导致DKA某些重要血液动力学和胃肠道特征的发病机制，环氧化酶抑制剂可能在部分患有该疾病的患者管理中发挥作用。α肾上腺素能活性对于维持DKA大鼠血浆TXB2水平升高至关重要。α肾上腺素能阻滞剂作用期间血浆TXB2水平下降似乎反映了血小板聚集和血小板TXA2生成受到抑制，但不排除DKA中血浆TXB2水平升高的其他来源。β肾上腺素能活性有助于维持实验性DKA中升高的循环血糖、游离脂肪酸和总酮体水平，但对前列腺素衍生物的血浆水平升高无作用。
