在今井大鼠中，血管紧张素Ⅱ1型受体阻断可预防蛋白尿、肾衰竭、高脂血症和肾小球硬化。

AT-1 receptor blockade prevents proteinuria, renal failure, hyperlipidemia, and glomerulosclerosis in the Imai rat.

作者信息

Rodríguez-Iturbe Bernardo, Sato Tadashi, Quiroz Yasmir, Vaziri Nosratola D

机构信息

Hospital Universitario, Universidad del Zulia and Instituto de Investigaciones Biomédicas, Maracaibo, Venezuela.

出版信息

Kidney Int. 2004 Aug;66(2):668-75. doi: 10.1111/j.1523-1755.2004.00789.x.

DOI:10.1111/j.1523-1755.2004.00789.x

PMID:15253721

Abstract

BACKGROUND

The Imai rat is a model of spontaneous focal glomerulosclerosis which leads to nephrotic syndrome, hyperlipidemia, hypertension, and progressive renal failure. We evaluated the effects of angiotensin II receptor type 1 (AT-1)blockade, and compared the results with the effects of the administration of hypolipidemic treatment with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. All treatments were started at 10 weeks of age when the rats were already proteinuric and continued for 6 months when rats were sacrificed.

METHODS

The following groups (N= 6 each) were studied: (1) control Sprague-Dawley rats, 34 weeks old; (2) Imai group that received vehicle; (3) Imai + angiotensin II receptor blockade (ARB) group that received olmesartan (10 mg/kg/day by gastric gavage); (4) Imai + prava group, that received pravastatin (20 mg/kg/day by gastric gavage); and (5) Imai + ARB + prava group that received both ARB and pravastatin. Lipid profile, renal function, and structure were assessed at 6 months.

RESULTS

As expected, the untreated Imai rats exhibited heavy proteinuria, hypoalbuminemia, hypertension, renal insufficiency, marked glomerulosclerosis, tubulointerstitial inflammation, and profound hyperlipidemia. Pravastatin treatment alone led to a significant, but partial improvement of hyperlipidemia and renal disease. The ARB treatment alone or in combination with pravastatin resulted in normalization of the blood pressure, urinary protein excretion, plasma cholesterol, triglycerides, low-density lipoproteins (LDLs), very low-density lipoproteins (VLDLs), and albumin concentrations and renal function. Significant glomerulosclerosis was prevented and tubulointerstitial injury and immune cell infiltration were reduced by long-term AT-1 blockade.

CONCLUSION

The study revealed that long-term AT-1 blockade corrects proteinuria, hyperlipidemia, and nephropathy in this model of spontaneous glomerulosclerosis.

摘要

背景

今井大鼠是一种自发性局灶性肾小球硬化模型，可导致肾病综合征、高脂血症、高血压和进行性肾衰竭。我们评估了1型血管紧张素II受体（AT-1）阻断的效果，并将结果与使用3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂进行降脂治疗的效果进行比较。所有治疗均在大鼠10周龄时开始，此时大鼠已出现蛋白尿，并持续6个月，之后处死大鼠。

方法

研究了以下几组（每组N = 6）：（1）34周龄的对照斯普拉格-道利大鼠；（2）接受赋形剂的今井组；（3）接受奥美沙坦（通过灌胃给予10 mg/kg/天）的今井 + 血管紧张素II受体阻断（ARB）组；（4）接受普伐他汀（通过灌胃给予20 mg/kg/天）的今井 + 普伐组；以及（5）接受ARB和普伐他汀的今井 + ARB + 普伐组。在6个月时评估血脂谱、肾功能和结构。

结果

正如预期的那样，未经治疗的今井大鼠表现出大量蛋白尿、低白蛋白血症、高血压、肾功能不全、明显的肾小球硬化、肾小管间质炎症和严重的高脂血症。单独使用普伐他汀治疗可导致高脂血症和肾脏疾病有显著但部分的改善。单独使用ARB治疗或与普伐他汀联合使用可使血压、尿蛋白排泄、血浆胆固醇、甘油三酯、低密度脂蛋白（LDL）、极低密度脂蛋白（VLDL）和白蛋白浓度以及肾功能恢复正常。长期的AT-1阻断可预防明显的肾小球硬化，并减少肾小管间质损伤和免疫细胞浸润。