High dietary protein exacerbates hypertension and renal damage in Dahl SS rats by increasing infiltrating immune cells in the kidney.
High dietary protein exacerbates hypertension and renal damage in Dahl SS rats by increasing infiltrating immune cells in the kidney.
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DOI：
10.1161/hypertensionaha.110.154302
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
Mattson DL
中科院分区：
文献类型：
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作者：
De Miguel C;Lund H;Mattson DL
本研究旨在探讨膳食蛋白质摄入对Dahl SS高血压和肾脏疾病的影响及其作用机制。从5~12周龄开始，饲喂含低(6%)、正常(18%)或高(30%)蛋白质和0.4%氯化钠的等热量饲料，然后在12~15周龄将饲料中的氯化钠含量提高到4.0%。与正常饮食组(132±3 mm Hg，1.2±0.3)和低蛋白饮食组(132±6 mm Hg，0.3±0.1)相比，高蛋白饮食组大鼠的MAP和尿白蛋白/肌酐比值(分别为153±7 mm Hg和8.0±2.4)最高。高蛋白饲料喂养的SS大鼠肾脏浸润性T淋巴细胞数量(18.9±3×105个)明显多于低蛋白饲料喂养的SS大鼠(9.1±3×105个细胞)。此外，用免疫抑制剂霉酚酸酯(20 mg/kg/d，ip)喂饲高蛋白饲料的SS大鼠，肾脏浸润性T细胞数(由18.9±2.7个降至10.6±2.0×105个)显著减少，血压(由133±3个降至113±4 mm Hg)和白蛋白/肌酐比值(由10.9±2.3个降至5.4±1.2个)明显降低。这些结果表明，限制蛋白质摄入对Dahl SS大鼠的高血压和肾脏疾病具有保护作用，提示免疫细胞的渗入在高蛋白饲料喂养的Dahl SS大鼠中起着病理作用。此外，结果表明Dahl SS大鼠的高血压对氯化钠和蛋白质摄入量都很敏感。
The present study evaluated the influence and mechanism of action of dietary protein intake in Dahl SS hypertension and renal disease. Rats were fed isocaloric diets with low (6%), normal (18%), or high (30%) amounts of protein and 0.4% NaCl from 5 to 12 weeks of age; the NaCl content of the diets was then increased to 4.0% NaCl from 12 to 15 weeks of age. Rats fed the high protein diet developed the highest MAP and urine albumin to creatinine ratio when fed the 4.0% NaCl diet (153±7 mmHg and 8.0±2.4, respectively) compared to rats fed normal (132±3 mmHg, 1.2±0.3) or low protein diets (132±6mmHg, 0.3±0.1). Significantly greater numbers of infiltrating T-lymphocytes were observed in kidneys of SS rats fed the high protein diet (18.9 ± 3 × 105 cells) than in rats fed the low protein diet (9.1 ± 3 × 105 cells). Furthermore, treatment of SS rats fed the high protein diet with the immunosuppressant agent mycophenolate mofetil (20mg/kg/day, ip) significantly reduced the number of infiltrating T cells in the kidneys (from 18.9 ± 2.7 to 10.6 ± 2.0 × 105 cells) while decreasing blood pressure (from 133 ± 3 to 113 ± 4 mmHg) and the albumin/creatinine ratio (from 10.9 ± 2.3 to 5.4 ± 1.2). These results demonstrate that restriction of protein intake protects the Dahl SS from hypertension and kidney disease and indicates that infiltrating immune cells play a pathological role in Dahl SS rats fed a high protein diet. Moreover, the results show that hypertension in Dahl SS rats is sensitive to both NaCl and protein intake.