维生素E可改善 Dahl 盐敏感大鼠的肾损伤。

Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats.

作者信息

Atarashi K, Ishiyama A, Takagi M, Minami M, Kimura K, Goto A, Omata M

机构信息

2nd Department of Internal Medicine, The University of Tokyo, Bunkyo-ku, Japan.

出版信息

Am J Hypertens. 1997 May;10(5 Pt 2):116S-119S.

PMID:9160794

Abstract

Recently, hyperlipidemia as well as hypertension has been observed in Dahl salt-sensitive (S) rats. In this study, to investigate whether the lipid abnormality is involved in the renal injury of Dahl S rats, we examined the effect of vitamin E on glomerular sclerosis, as vitamin E is an inhibitor of lipid oxidation. Dahl S rats were given a high salt diet (8% NaCl) containing either normal vitamin E (2 mg/100 g) or high vitamin E (50 mg/100 g) for 4 weeks. Dahl salt-resistant (R) rats were given a high salt and normal vitamin E diet. The blood pressure in the Dahl rats increased and was not suppressed by the vitamin E supplement. Serum cholesterol and triglycerides in Dahl S rats were higher than in Dahl R rats at both 0 and 4 weeks. Vitamin E lowered the serum cholesterol level in Dahl S rats at 4 weeks (126 +/- 5 v 150 +/- 12 mg/dL, P < .01). Urinary protein excretion and serum creatinine increased in Dahl S rats, and vitamin E inhibited the increases significantly (urinary protein, 70.7 +/- 0.9 v 178.0 +/- 8.8 mg/day, P < .01; serum creatinine, 0.45 +/- 0.02 v 0.63 +/- 0.05 mg/dL, P < .01). Serum lipid peroxide (LPO) was higher in Dahl S rats than in Dahl R rats, and vitamin E lowered LPO in Dahl S rats (2.10 +/- 0.03 v 2.70 +/- 0.04 nmol/mL, P < .01). In the histologic study, sclerosing score (SS) of glomeruli, which represents the degree of glomerulosclerosis semiquantitatively, was higher in Dahl S rats than in Dahl R rats. Vitamin E lowered SS (114 +/- 3 v 157 +/- 6, P < .01) and ameliorated arterial injuries such as medial thickness with partial necrosis and severe fibrinoid proliferation with inflammatory cell infiltration. In all rats, SS was strongly correlated with urinary protein (r = 0.93, P < .01), serum cholesterol (r = 0.86, P < .01), and serum LPO (r = 0.89, P < .01). These results suggest that the renal injury in Dahl S rats is caused not only by hypertension but also by hyperlipidemia. Therefore, vitamin E might ameliorate the renal damage by inhibiting the oxidation of lipids.

摘要

最近，在 Dahl 盐敏感（S）大鼠中观察到了高脂血症和高血压。在本研究中，为了探究脂质异常是否参与 Dahl S 大鼠的肾损伤，我们研究了维生素 E 对肾小球硬化的影响，因为维生素 E 是脂质氧化的抑制剂。给 Dahl S 大鼠喂食含正常维生素 E（2 mg/100 g）或高剂量维生素 E（50 mg/100 g）的高盐饮食（8% NaCl），持续 4 周。给 Dahl 盐抵抗（R）大鼠喂食高盐和正常维生素 E 饮食。Dahl 大鼠的血压升高，补充维生素 E 后未得到抑制。在第 0 周和第 4 周时，Dahl S 大鼠的血清胆固醇和甘油三酯均高于 Dahl R 大鼠。维生素 E 降低了 Dahl S 大鼠第 4 周时的血清胆固醇水平（126±5 对 150±12 mg/dL，P<.01）。Dahl S 大鼠的尿蛋白排泄和血清肌酐增加，维生素 E 显著抑制了这些增加（尿蛋白，70.7±0.9 对 178.0±8.8 mg/天，P<.01；血清肌酐，0.45±0.02 对 0.63±0.05 mg/dL，P<.01）。Dahl S 大鼠的血清脂质过氧化物（LPO）高于 Dahl R 大鼠，维生素 E 降低了 Dahl S 大鼠的 LPO（2.10±0.03 对 2.70±0.04 nmol/mL，P<.01）。在组织学研究中，代表肾小球硬化程度的肾小球硬化评分（SS）在 Dahl S 大鼠中高于 Dahl R 大鼠。维生素 E 降低了 SS（114±3 对 157±6，P<.01），并改善了动脉损伤，如伴有部分坏死的中层增厚以及伴有炎症细胞浸润的严重纤维蛋白样增生。在所有大鼠中，SS 与尿蛋白（r = 0.93，P<.01）、血清胆固醇（r = 0.86，P<.01）和血清 LPO（r = 0.89，P<.01）密切相关。这些结果表明，Dahl S 大鼠的肾损伤不仅由高血压引起，还由高脂血症引起。因此，维生素 E 可能通过抑制脂质氧化来改善肾损伤。