Masumura H, Kunitada S, Irie K, Ashida S, Abe Y
Department of Pharmacology, Kagawa Medical School, Japan.
Eur J Pharmacol. 1992 Jan 14;210(2):163-72. doi: 10.1016/0014-2999(92)90667-s.
Spontaneously hypertensive rats (SHR) were injected with streptozotocin (STZ-SHR) to induce diabetes. The effect of DP-1904, a thromboxane A2 synthetase inhibitor, on diabetic nephropathy was then studied by administering it for 5 months (1 or 10 mg/kg). DP-1904 did not affect renal 6-keto prostaglandin (PG)F1 alpha production in STZ-SHR, but markedly inhibited renal thromboxane (TX) B2 production, so that the 6-keto PGF1 alpha/TXB2 ratio was significantly increased (P less than 0.05). STZ-SHR showed significant uraemia and proteinuria, plus increases in urinary gamma-glutamyl-transpeptidase and urinary N-acetyl-beta-glucosaminidase. DP-1904 significantly decreased (P less than 0.01) the urinary changes. STZ-SHR also showed an increase in mesangial periodic acid-Schiff-positive substance and in relative renal weight, both of which were significantly inhibited by DP-1904 (P less than 0.05). Thus, DP-1904 inhibited both TXB2 production and the progression of renal damage in STZ-SHR.
给自发性高血压大鼠（SHR）注射链脲佐菌素（STZ-SHR）以诱导糖尿病。然后通过给予血栓素A2合成酶抑制剂DP-1904 5个月（1或10毫克/千克）来研究其对糖尿病肾病的影响。DP-1904不影响STZ-SHR中肾6-酮前列腺素（PG）F1α的产生，但显著抑制肾血栓素（TX）B2的产生，从而使6-酮PGF1α/TXB2比值显著增加（P<0.05）。STZ-SHR出现明显的尿毒症和蛋白尿，同时尿γ-谷氨酰转肽酶和尿N-乙酰-β-葡萄糖苷酶增加。DP-1904显著降低（P<0.01）尿液变化。STZ-SHR还表现出系膜过碘酸希夫阳性物质增加和相对肾重量增加，两者均被DP-1904显著抑制（P<0.05）。因此，DP-1904抑制了STZ-SHR中TXB2的产生和肾损伤的进展。
