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过氧化氢诱导的肾小球损伤:血管紧张素转换酶抑制剂的调节作用

Glomerular injury induced by hydrogen peroxide: modifying influence of ACE inhibitors.

作者信息

Clayton L, Hiley C, Davies S, D'Souza R, Jones P, Strange R, Aber G

机构信息

Renal Laboratory School of Postgraduate Medicine, Keele University, North Staffordshire Hospital Centre, Stoke-on-Trent, UK.

出版信息

Free Radic Res Commun. 1992;17(4):271-8. doi: 10.3109/10715769209079519.

DOI:10.3109/10715769209079519
PMID:1473736
Abstract

The sensitivity of isolated glomeruli from normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SHR) strains to oxidant stress was studied by determining the incidence of pyknosis, karyohexis and karyolysis after incubation with different concentrations of hydrogen peroxide (H2O2) (4.7 x 10(-9) - 10(-3) M). Even though the proportion of glomeruli containing nuclei that demonstrated these features increased progressively with increasing concentrations of H2O2, the number of severely damaged glomeruli was relatively small even at concentrations of 4.7 x 10(-3) M. Examination of the surface epithelial cells of glomeruli using scanning electron microscopy revealed no evidence of disturbance of the macroscopic or podocyte structure or, of increased blebbing after H2O2-treatment. These data suggest damage to nuclei is an early result of ROS stress on glomeruli. Preincubation of WKY glomeruli with captopril or lisinopril resulted in a significant drop in the proportion of WKY glomeruli demonstrating structural damage after oxidant stress. In contrast, preincubation of SHR glomeruli with lisinopril had no effect on oxidant-induced changes in the morphology of SHR glomeruli, whereas captopril effected a significant increase in the proportion of glomeruli demonstrating damage at all concentration of H2O2.

摘要

通过测定与不同浓度过氧化氢(H₂O₂)(4.7×10⁻⁹ - 10⁻³ M)孵育后核固缩、核破裂和核溶解的发生率,研究了来自正常血压(Wistar-Kyoto,WKY)和自发性高血压(SHR)品系的分离肾小球对氧化应激的敏感性。尽管显示这些特征的含核肾小球比例随着H₂O₂浓度的增加而逐渐增加,但即使在4.7×10⁻³ M的浓度下,严重受损的肾小球数量也相对较少。使用扫描电子显微镜检查肾小球的表面上皮细胞,未发现H₂O₂处理后宏观结构或足细胞结构受到干扰或泡状化增加的证据。这些数据表明细胞核损伤是ROS对肾小球应激的早期结果。用卡托普利或赖诺普利预孵育WKY肾小球,导致氧化应激后显示结构损伤的WKY肾小球比例显著下降。相比之下,用赖诺普利预孵育SHR肾小球对氧化应激诱导的SHR肾小球形态变化没有影响,而卡托普利在所有H₂O₂浓度下均使显示损伤的肾小球比例显著增加。

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