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Establishment of a novel strain of spontaneously hypertensive rat with a defect of ascorbic acid biosynthesis, and the effect of ascorbic acid deficiency on the hypertension

抗坏血酸生物合成缺陷型自发性高血压大鼠新品系的建立及抗坏血酸缺乏对高血压的影响

基本信息

批准号：
11660125
负责人：
HORIO Fumihiko
金额：
$ 2.3万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

To investigate the effects of ascorbic acid deficiency on the pathogenesis of hypertension and/or its complications, establishment of a rat strain with both genetic hypertension and a defect of ascorbic acid biosynthesis was conducted. The od gene (L-gulono-γ-lactone oxidase gene) of ODS rat, which is a rat mutant unable to synthesize ascorbic acid, was introduced into spontaneously hypertensive rats (SHR) and a novel congenic strain, SHR-od, was established. SHR-od showed scurvy when fed an ascorbic acid-free diet. Systolic blood pressure of male SHR-od began to increase at 9 weeks of age, and reached 190-200mmHg at 20 weeks of age. In 25-week-old SHR-od, ascorbic acid deficiency when fed ant ascorbic acid-free diet for 6 weeks caused a remarkable reduction of blood pressure lower than 110mmHg. The wall to lumen ratio of testicular artery in ascorbic acid-deficient SHR-od was lower than that of the control rats. When fed a diet supplemented with ascorbic acid (300mg/kg), ascorbic acid concentration in SHR-od was lower in the serum and liver than in ODS rats. These results indicate that ascorbic acid could be closely related to the development of hypertension in SHR-od. It is expected that SHR-od will be a useful model for experimental studies on hypertension and its complications, since all of them suffer from hypertension spontaneously and the level of ascorbic acid deficiencv in these rats could be controlled at will both in concentration and duration.

为探讨抗坏血酸缺乏对高血压及其并发症发病机制的影响，建立了遗传性高血压和抗坏血酸生物合成缺陷的大鼠品系。将不能合成抗坏血酸的ODS大鼠的od基因（L-古洛糖酸-γ-内酯氧化酶基因）导入自发性高血压大鼠（SHR），建立了一个新的同类品系SHR-od。SHR-od在喂食无抗坏血酸饮食时显示坏血病。雄性SHR-od的收缩压从9周龄开始升高，20周龄达190- 200 mmHg。在25周龄SHR-od中，给予无抗坏血酸饮食6周后，抗坏血酸缺乏可使血压显著降低至110 mmHg以下。抗坏血酸缺乏的SHR-od大鼠睾丸动脉壁腔比低于对照组。当饲料中添加抗坏血酸（300 mg/kg）时，SHR-od大鼠血清和肝脏中的抗坏血酸浓度低于ODS大鼠。提示抗坏血酸可能与自发性高血压的发生发展密切相关。由于自发性高血压大鼠均患有高血压，且抗坏血酸缺乏的浓度和持续时间可任意控制，因此，SHR-od可望成为高血压及其并发症实验研究的一个有用模型。