普罗布考对大鼠肾次全切除术后肾小球抗氧化酶mRNA表达的影响。

Effect of probucol on mRNA expression of glomerular antioxidant enzymes in rat with subtotal nephrectomy.

作者信息

Tang Z, Ji D, Li L, Fukui M, Tomino Y, Koide H

机构信息

Department of Nephrology, Jinling Hospital, School of Medicine, Nanjing University.

出版信息

Chin Med J (Engl). 1996 Oct;109(10):780-6.

PMID:9275355

Abstract

OBJECTIVE

To investigate 1) the glomerular mRNA expression and protein activity of antioxidant enzymes (AOEs) including superoxide dismutase (SOD) and glutathine peroxidase (GSH-Px) and the glomerular content of lipid peroxide-malondiadehyde (MDA), 2) the effects of probucol (P), a potent antioxidant agent on these AOEs and MDA levels, in the chronic phase of subtotal nephrectomized rats.

METHODS

The adult male Spregue-Dawley rats were randomly divided into three groups at the first week after subtotal renal ablation. Group 1 was sham rats (sham n = 8), group 2 underwent 5/6 nephrectomy without special therapy (5/6 Nx n = 8), and group 3 with 5/6 nephrectomy received probucol (5/6 Nxs+P n = 8) at a dose of 1% in the rat chow. At the 12th week after P was administrated, all of the rats were sacrificed to remove left kidney for the determination of glomerular level of MDA, activity of SOD, and GSH-Px, glomerular mRNA expression of AOEs by Northern blot analysis as well as a histological examination.

RESULTS

In 5/6 Nx, serum cholesterol, proteinuria increased and creatinine clearance decreased progressively with age as compared with that in sham. Those abnormalities as well as glomerulosclerosis index (GI) ameliorated with the administration of probucol at the 12th week after subtotal nephrectomy [GI: sham 3.12 +/- 1.20, P < 0.01 vs 5/6 Nx 5/6 Nx 188.6 +/- 25.1; 5/6 Nx +/- P, 106.9 +/- 17.6, P < 0.05 vs 5/6 Nx]. The probucol therapy also significantly improved the decrease of glomerular Mn-SOD and GSH-Px both at mRNA level and protein activity and the increase of glomerular MDA content.

CONCLUSIONS

We demonstrated a deficiency of glomerular AOEs in the chronic phase of remnant kidney, which may contribute to the progression of renal injury. The protective effects of probucol on both renal functional impairment and the development of glomerulosclerosis may be partially associated with improving surviving glomerular AOEs.

摘要

目的

研究1）抗氧化酶（AOEs）包括超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的肾小球mRNA表达和蛋白活性以及脂质过氧化物丙二醛（MDA）的肾小球含量，2）普罗布考（P），一种强效抗氧化剂，对次全肾切除大鼠慢性期这些AOEs和MDA水平的影响。

方法

成年雄性Sprague-Dawley大鼠在次全肾切除术后第一周随机分为三组。第1组为假手术大鼠（假手术组n = 8），第2组接受5/6肾切除术且无特殊治疗（5/6 Nx组n = 8），第3组接受5/6肾切除术并在大鼠饲料中给予剂量为1%的普罗布考（5/6 Nxs + P组n = 8）。在给予普罗布考后的第12周，处死所有大鼠，取出左肾用于测定肾小球MDA水平、SOD和GSH-Px活性、通过Northern印迹分析测定AOEs的肾小球mRNA表达以及进行组织学检查。

结果

与假手术组相比，在5/6 Nx组中，血清胆固醇、蛋白尿随年龄逐渐增加，肌酐清除率逐渐降低。在次全肾切除术后第12周给予普罗布考后，这些异常以及肾小球硬化指数（GI）得到改善[GI：假手术组3.12±1.20，与5/6 Nx组5/6 Nx 188.6±25.1相比，P < 0.01；5/6 Nx±P组，106.9±17.6，与5/6 Nx组相比，P < 0.05]。普罗布考治疗还显著改善了肾小球锰超氧化物歧化酶（Mn-SOD）和谷胱甘肽过氧化物酶（GSH-Px）在mRNA水平和蛋白活性的降低以及肾小球MDA含量的增加。