Wapstra F H, Navis G J, van Goor H, van den Born J, Berden J H, de Jong P E, de Zeeuw D
Division of Nephrology, Groningen University Institute for Drug Exploration, Nijmegen, The Netherlands.
Exp Nephrol. 2001;9(1):21-7. doi: 10.1159/000020704.
The gradual onset of the antiproteinuric effects of ACE inhibition suggests that structural effects on the glomerular basement membrane (GBM) may be involved in their renoprotective action. To test this hypothesis, we studied the effects of lisinopril (5 mg/kg/24 h) on proteinuria, focal glomerulosclerosis (FGS) and glomerular heparan sulfate (HS) proteoglycan (HSPG) GBM staining in rats with established Adriamycin nephrosis. Treatment was started 6 weeks after disease induction. As expected, lisinopril reduced blood pressure, proteinuria and the FGS score. In control rats, Adriamycin nephrosis was associated with significantly impaired GBM staining for both HSPG core protein (assessed from BL-31 staining) and HS staining (assessed from JM-403 staining) 12 weeks after disease induction. In rats treated with lisinopril (5 mg/kg/24 h) GBM staining was significantly better preserved for HS as well as for HSPG core protein. These data suggest that structural effects on the GBM, improving glomerular permselectivity, may be involved in the renoprotective effects of ACE inhibition in proteinuria-induced renal damage.
血管紧张素转换酶（ACE）抑制作用的抗蛋白尿效应逐渐显现，这表明其对肾小球基底膜（GBM）的结构影响可能参与了肾脏保护作用。为验证这一假说，我们研究了赖诺普利（5毫克/千克/24小时）对阿霉素肾病大鼠蛋白尿、局灶性肾小球硬化（FGS）及肾小球硫酸乙酰肝素（HS）蛋白聚糖（HSPG）在GBM上染色的影响。在疾病诱导6周后开始治疗。如预期的那样，赖诺普利降低了血压、蛋白尿及FGS评分。在对照大鼠中，疾病诱导12周后，阿霉素肾病与HSPG核心蛋白（通过BL - 31染色评估）及HS染色（通过JM - 403染色评估）的GBM染色显著受损有关。在用赖诺普利（5毫克/千克/24小时）治疗的大鼠中，HS及HSPG核心蛋白的GBM染色得到了显著更好的保存。这些数据表明，对GBM的结构影响，改善肾小球的选择性通透性，可能参与了ACE抑制在蛋白尿诱导的肾损伤中的肾脏保护作用。
