Erman A, Chen-Gal B, Rosenfeld J
Institute of Nephrology and Hypertension, Beilinson Medical Center, Petah Tikva, Israel.
J Pharm Pharmacol. 1990 Mar;42(3):181-5. doi: 10.1111/j.2042-7158.1990.tb05381.x.
This study was designed to investigate the effects of chronic treatment with cyclosporin A (CSA) on the endogenous synthesis of prostanoids (PGs) and thromboxane (Tx) by renal isolated medullary and cortical mitochondria. The administration of CSA, dissolved in 10% ethanol in olive oil, to male Wistar rats (20 mg kg-1 day-1 i.p.) for 14 days resulted in alterations in mitochondrial biosynthesis of immunoreactive PGs. The endogenous synthesis of thromboxane by medullary and cortical mitochondria isolated from CSA-treated rats was significantly enhanced by 120 and 55%, respectively, whereas the synthesis of prostaglandin E2 by medullary mitochondria was reduced by 35%. The synthesis of prostaglandin F2 alpha and prostacyclin was not affected by CSA treatment. The conversion of exogenous arachidonic acid to PGs and Tx by cortical mitochondria isolated from CSA-treated rats was significantly increased. In addition, CSA treatment resulted in i) a reduced acylation of arachidonic acid into medullary phospholipids by 25% and into medullary and cortical triglycerides by 33 and 27%, respectively, and ii) an increase in cortical and medullary triglycerides. We suggest that the alterations in the endogenous mitochondrial production of PGs and Tx caused by CSA, may play a role in the impairment of membrane mediated functions.
本研究旨在探讨环孢素A（CSA）长期治疗对肾分离髓质和皮质线粒体中前列腺素（PGs）和血栓素（Tx）内源性合成的影响。将溶解于10%乙醇橄榄油溶液中的CSA以20mg kg-1 天-1腹腔注射给雄性Wistar大鼠，持续14天，结果导致免疫反应性PGs的线粒体生物合成发生改变。从CSA处理的大鼠分离的髓质和皮质线粒体中血栓素的内源性合成分别显著增强了120%和55%，而髓质线粒体中前列腺素E2的合成减少了35%。前列腺素F2α和前列环素的合成不受CSA处理的影响。从CSA处理的大鼠分离的皮质线粒体将外源性花生四烯酸转化为PGs和Tx的能力显著增加。此外，CSA处理导致：i）花生四烯酸酰化进入髓质磷脂的量减少25%，进入髓质和皮质甘油三酯的量分别减少33%和27%；ii）皮质和髓质甘油三酯增加。我们认为，CSA引起的PGs和Tx内源性线粒体产生的改变，可能在膜介导功能受损中起作用。
