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不同剂量阿托伐他汀对肾小管细胞的影响:一项实验研究。

The effect of the various doses of atorvastatin on renal tubular cells; an experimental study.

作者信息

Nasri Hamid, Hasanpour Zahra, Nematbakhsh Mehdi, Ahmadi Ali, Rafieian-Kopaei Mahmoud

机构信息

Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran ; Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

出版信息

J Nephropathol. 2016 Jul;5(3):111-5. doi: 10.15171/jnp.2016.20. Epub 2016 Feb 14.

Abstract

BACKGROUND

Recent retrospective observational studies suggest that high-potency statin therapy might increase the risk of acute kidney injury, however data on this subject is scares.

OBJECTIVES

This study, was designed to investigate the renal tubular cell effect of different doses of atorvastatin to detect the possible aggravation of renal function or morphology of the kidney.

MATERIALS AND METHODS

In this experimental study 24 male Wistar rats were designated into 4 equal groups and treated as follows. Control group received phosphate buffer as the vehicle of atorvastatin for 7 days. Groups 1, II and III received atorvastatin at doses of 10, 50 and 150 mg/kg daily for 7 days, then on the day 8, all rats were anesthetized using ketamine and the blood samples were collected for evaluation of creatinine (Cr) and blood urea nitrogen (BUN) levels and then all rats were sacrificed, then the animals' kidneys were dissected out and histopathological studies were performed.

RESULTS

Mean (±SD) of scores of injury to renal tubular cells in control group was 4.2 ± 2.2 and in groups I, II and III were 6.44 ± 4.9, 15.4 ± 8.5 and 25.8 ± 12.7 respectively. Group III which received 150 mg/kg/day of atorvastatin had significant renal damage in comparison to control group (P < 0.001). There was no significant difference of renal injury score between control group with groups of I and II.

CONCLUSIONS

In the present study we found, atorvastatin with a dose of 150 mg/kg/day for 7 days was nephrotoxic for rats, while lower doses at 10 mg/kg/day or 50 mg/kg/day for 7 days were not accompanied by renal injury. These findings imply further attention to the administration of higher doses of atorvastatin in clinical conditions.

摘要

背景

近期的回顾性观察研究表明,高强度他汀类药物治疗可能会增加急性肾损伤的风险,然而关于这一主题的数据却很匮乏。

目的

本研究旨在调查不同剂量阿托伐他汀对肾小管细胞的影响,以检测肾功能或肾脏形态是否可能加重。

材料与方法

在这项实验研究中,将24只雄性Wistar大鼠分为4组,每组数量相等,并进行如下处理。对照组接受磷酸盐缓冲液作为阿托伐他汀的载体,持续7天。第1组、第2组和第3组分别每天接受10、50和150mg/kg的阿托伐他汀,持续7天。然后在第8天,所有大鼠使用氯胺酮麻醉,采集血样以评估肌酐(Cr)和血尿素氮(BUN)水平,随后处死所有大鼠,取出动物的肾脏并进行组织病理学研究。

结果

对照组肾小管细胞损伤评分的平均值(±标准差)为4.2±2.2,第1组、第2组和第3组分别为6.44±4.9、15.4±8.5和25.8±12.7。与对照组相比,接受150mg/kg/天阿托伐他汀的第3组有明显的肾损伤(P<0.001)。对照组与第1组和第2组之间的肾损伤评分无显著差异。

结论

在本研究中,我们发现,每天150mg/kg剂量的阿托伐他汀连续使用7天对大鼠具有肾毒性,而每天10mg/kg或50mg/kg的较低剂量连续使用7天未伴有肾损伤。这些发现意味着在临床情况下,应进一步关注高剂量阿托伐他汀的使用。

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Statins, inflammation and kidney disease.他汀类药物、炎症与肾脏疾病。
Nat Rev Nephrol. 2011 May 31;7(7):385-97. doi: 10.1038/nrneph.2011.62.

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