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瑞舒伐他汀降脂治疗对糖尿病肾病患者肾功能和氧化应激的影响。

Effects of lipid-lowering therapy with rosuvastatin on kidney function and oxidative stress in patients with diabetic nephropathy.

机构信息

Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.

出版信息

J Atheroscler Thromb. 2011;18(11):1018-28. doi: 10.5551/jat.9084. Epub 2011 Sep 15.

Abstract

AIM

We aimed to assess the effects of rosuvastatin treatment on lipid levels, a biomarker of oxidative stress, albuminuria, and kidney function in patients with diabetic nephropathy.

METHODS

We conducted a prospective, open-label, parallel group, controlled study of 104 patients with diabetic nephropathy, low-density lipoprotein cholesterol (LDL-C) levels of > 120 mg/dL, and well-controlled blood pressure who were undergoing treatment with renin angiotensin system inhibitors. Patients were randomly assigned to two groups: the rosuvastatin group (n = 52; 2.5 mg/day rosuvastatin, increased to 10 mg/day) and the control group (n = 52; no rosuvastatin administered). We determined the efficacy of rosuvastatin by monitoring serum lipid profiles, high sensitivity C-reactive protein (hs-CRP), malondialdehyde-modified LDL (MDA-LDL), and cystatin C levels. In addition, urinary albumin, 8-hydroxydeoxyguanosine (8-OHdG) and liver-type fatty acid-binding protein (L-FABP) levels were measured before and 6 months after rosuvastatin was added to the treatment.

RESULTS

Rosuvastatin effectively reduced total cholesterol, LDL-C, triglycerides, non-high-density lipoprotein cholesterol (non-HDL-C) levels, and the LDL-C/ HDL-C ratio in the rosuvastatin group. These parameters remained unchanged in patients who were not treated with rosuvastatin. Although there was no significant change in the estimated glomerular filtration rate level, serum cystatin C levels and urinary albumin excretion rates were significantly decreased in the rosuvastatin group. In addition, rosuvastatin significantly reduced hs-CRP and MDA-LDL levels. Moreover, urinary 8-OHdG and L-FABP levels at baseline (13.5±5.1 and 41.7±26.1 ng/mgCr, respectively) decreased significantly at 6 months (11.5±4.0 and 26.9±13.4 ng/mgCr, respectively), and there was a significant correlation (r = 0.48, p < 0.01). Multivariate analysis revealed that albuminuria was significantly correlated with only rosuvastatin use (p = 0.0006, R(2)= 0.53).

CONCLUSION

Rosuvastatin administration reduced albuminuria, oxidative stress, and serum cystatin C levels, independent of blood pressure and lipid levels.

摘要

目的

评估瑞舒伐他汀治疗对糖尿病肾病患者的血脂水平、氧化应激标志物、白蛋白尿和肾功能的影响。

方法

我们进行了一项前瞻性、开放标签、平行组、对照研究,纳入了 104 例糖尿病肾病、低密度脂蛋白胆固醇(LDL-C)水平>120mg/dL 且血压控制良好的患者,这些患者正在接受肾素-血管紧张素系统抑制剂治疗。患者被随机分为两组:瑞舒伐他汀组(n=52;瑞舒伐他汀 2.5mg/天,增至 10mg/天)和对照组(n=52;未给予瑞舒伐他汀)。我们通过监测血清脂质谱、高敏 C 反应蛋白(hs-CRP)、丙二醛修饰的 LDL(MDA-LDL)和胱抑素 C 水平来确定瑞舒伐他汀的疗效。此外,在添加瑞舒伐他汀治疗前和治疗 6 个月后,测量尿白蛋白、8-羟基脱氧鸟苷(8-OHdG)和肝型脂肪酸结合蛋白(L-FABP)水平。

结果

瑞舒伐他汀可有效降低瑞舒伐他汀组的总胆固醇、LDL-C、甘油三酯、非高密度脂蛋白胆固醇(non-HDL-C)水平和 LDL-C/HDL-C 比值。未接受瑞舒伐他汀治疗的患者这些参数保持不变。尽管估算的肾小球滤过率水平没有显著变化,但瑞舒伐他汀组的血清胱抑素 C 水平和尿白蛋白排泄率显著降低。此外,瑞舒伐他汀可显著降低 hs-CRP 和 MDA-LDL 水平。此外,基线时的尿 8-OHdG 和 L-FABP 水平(分别为 13.5±5.1 和 41.7±26.1ng/mgCr)在 6 个月时显著下降(分别为 11.5±4.0 和 26.9±13.4ng/mgCr),且呈显著相关性(r=0.48,p<0.01)。多变量分析显示,白蛋白尿与瑞舒伐他汀的使用显著相关(p=0.0006,R2=0.53)。

结论

瑞舒伐他汀可降低白蛋白尿、氧化应激和血清胱抑素 C 水平,与血压和血脂水平无关。

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