Zoja C, Perico N, Bergamelli A, Pasini M, Morigi M, Dadan J, Belloni A, Bertani T, Remuzzi G
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
Kidney Int. 1990 Mar;37(3):934-42. doi: 10.1038/ki.1990.68.
Functional and morphological studies were done in three groups of male Sprague-Dawley rats after removal of the right kidney and infarction of approximately five-sixths of the left. Group 1 received no specific therapy. Group 2 was treated with ticlopidine, 150 mg/kg per os, for 50 days starting 10 days after surgical ablation. Group 3 was given the thromboxane antagonist, GR 32191, 3 mg/kg b.i.d. orally for 50 days, like ticlopidine. Untreated Group 1 rats developed renal insufficiency, systemic hypertension, progressive proteinuria and glomerulosclerosis. In Group 2 treatment with ticlopidine was associated with less severe impairment of renal function. Proteinuria was significantly lower and animals were partially protected from the development of glomerulosclerosis. These animals had significantly prolonged skin bleeding time. In vitro ADP and arachidonic acid (AA)-induced platelet aggregation was inhibited. Systemic blood pressure was significantly lower than in controls. In Group 3 rats GR 32191 failed to influence progressive proteinuria and severity of glomerulosclerosis which were comparable to those in Group 1. Bleeding time was not prolonged, and in vitro platelet aggregation was inhibited only when AA was used as aggregating agent. Systemic blood pressure was not influenced. These studies suggest that a drug like ticlopidine, which has a broad spectrum of pharmacological actions on platelets and platelet-cell interactions, does retard the development of progressive renal injury when nephron number is reduced. Specific blocking of thromboxane A2 (TxA2) biological activity does not influence progressive renal disease in rats with remnant kidney.
对三组雄性斯普拉格 - 道利大鼠进行了功能和形态学研究，这些大鼠在切除右肾且左肾约六分之五发生梗死之后进行研究。第1组未接受特殊治疗。第2组在手术切除10天后开始口服噻氯匹定，剂量为150mg/kg，持续50天。第3组与噻氯匹定组一样，口服血栓素拮抗剂GR 32191，剂量为3mg/kg，每日两次，持续50天。未经治疗的第1组大鼠出现肾功能不全、全身性高血压、进行性蛋白尿和肾小球硬化。在第2组中，噻氯匹定治疗与较轻的肾功能损害相关。蛋白尿显著降低，动物在一定程度上免受肾小球硬化的发展影响。这些动物的皮肤出血时间显著延长。体外，ADP和花生四烯酸（AA）诱导的血小板聚集受到抑制。全身血压显著低于对照组。在第3组大鼠中，GR 32191未能影响进行性蛋白尿和肾小球硬化的严重程度，其与第1组相当。出血时间未延长，仅在使用AA作为聚集剂时体外血小板聚集受到抑制。全身血压未受影响。这些研究表明，像噻氯匹定这样对血小板和血小板 - 细胞相互作用具有广泛药理作用的药物，在肾单位数量减少时确实会延缓进行性肾损伤的发展。特异性阻断血栓素A2（TxA2）的生物活性对残余肾大鼠的进行性肾病没有影响。
