Quilley J, McGiff J C
J Pharmacol Exp Ther. 1986 Aug;238(2):606-11.
Urinary prostaglandin (PG) and thromboxane (Tx) excretion, measured by radioimmunoassay, were examined in two groups of male Wistar rats made diabetic with streptozotocin, 70 mg/kg, one of which received daily insulin beginning on the 7th day after administration of streptozotocin. In addition, urinary kallikrein excretion and blood pressure were monitored. After the induction of diabetes the profile of urinary eicosanoid excretion was altered. 6-keto-PGF1 alpha and TxB2 excretion increased markedly within 24 to 48 hr and remained elevated for the duration of the study, up to 58 days. PGF2 alpha excretion also increased, the change being apparent after 6 days whereas PGE2 excretion was reduced at this time. Urinary kallikrein excretion was unchanged but blood pressure became elevated above control levels 2 weeks after the induction of diabetes. Insulin treatment, to maintain mean blood glucose levels below 200 mg/dl, resulted in decreased excretion of TxB2, PGF2 alpha and 6-keto-PGF1 alpha. However, excretion of PGE2 and kallikrein were increased after insulin treatment which also prevented the elevation in blood pressure. These studies indicate that insulin treatment of experimental diabetes corrects alterations in renal arachidonic acid metabolism and prevents the associated increase in blood pressure.
通过放射免疫分析法测定两组用70mg/kg链脲佐菌素诱导糖尿病的雄性Wistar大鼠的尿前列腺素(PG)和血栓素(Tx)排泄,其中一组在给予链脲佐菌素后第7天开始每日注射胰岛素。此外,监测尿激肽释放酶排泄和血压。糖尿病诱导后,尿类二十烷酸排泄情况发生改变。6-酮-前列腺素F1α和血栓素B2排泄在24至48小时内显著增加,并在长达58天的研究期间持续升高。前列腺素F2α排泄也增加,6天后变化明显,而此时前列腺素E2排泄减少。尿激肽释放酶排泄未改变,但糖尿病诱导后2周血压高于对照水平。胰岛素治疗使平均血糖水平维持在200mg/dl以下,导致血栓素B2、前列腺素F2α和6-酮-前列腺素F1α排泄减少。然而,胰岛素治疗后前列腺素E2和激肽释放酶排泄增加,且还防止了血压升高。这些研究表明,实验性糖尿病的胰岛素治疗可纠正肾花生四烯酸代谢改变,并防止相关的血压升高。