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西咪替丁和左旋肉碱对雄性大鼠肌红蛋白尿性急性肾损伤影响的研究

A study on the effect of cimetidine and L-carnitine on myoglobinuric acute kidney injury in male rats.

作者信息

Estaphan Suzanne, Eissa Hassan, Elattar Samah, Rashed Laila, Farouk Mira

机构信息

Physiology Department, Faculty of Medicine, Cairo University, Giza, Egypt.

Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Giza, Egypt.

出版信息

Injury. 2015 Jul;46(7):1223-30. doi: 10.1016/j.injury.2015.03.037. Epub 2015 Apr 11.

Abstract

Myoglobinuric acute renal failure is the most important life threatening complication of rhabdomyolysis. Iron, free radicals, nitric oxide and cytochrome p450 are involved in the pathogenesis of mARF. The aim of this study is to compare the effect of cimetidine, l-carnitine and both agents together on mARF in rats. Forty rats were divided into 5 groups; group I: control rats, group II: myoglobinuric ARF rats, group III: mARF rats received l-carnitine (200mg/kg, i.p.), group IV: mARF rats received cimetidine (150mg/kg i.p.) and group V: mARF rats received both agents together. 48h after glycerol injection, systolic blood pressure was measured. Urine and blood samples were collected to evaluate urine volume, GFR, BUN, creatinine, K, Na, serum creatine kinase, NO and glutathione levels. Kidney specimens were taken to investigate renal cytochrome p450 and for histological examinations. Cimetidine treatment significantly decreased creatinine, BUN, K, Na, SBP and creatine kinase and increased GFR and urine volume compared to group II. l-carnitine exerted similar changes except for the effect on K and GFR. NO was significantly decreased, while renal glutathione and cytochrome p450 were significantly increased in groups treated with l-carnitine or cimetidine as compared to group II. Combined treatment further improved renal functions, creatine kinase, oxidative stress parameters and SBP as compared to each therapy alone. The histological changes confirmed the biochemical findings. Cimetidine and l-carnitine have protective effects - almost equally - against mARF. Using both agents together, minimises the renal injury.

摘要

肌红蛋白尿性急性肾衰竭是横纹肌溶解症最重要的危及生命的并发症。铁、自由基、一氧化氮和细胞色素P450参与了肌红蛋白尿性急性肾衰竭的发病机制。本研究的目的是比较西咪替丁、左旋肉碱以及两者联合使用对大鼠肌红蛋白尿性急性肾衰竭的影响。40只大鼠被分为5组;第一组:对照大鼠;第二组:肌红蛋白尿性急性肾衰竭大鼠;第三组:接受左旋肉碱(200mg/kg,腹腔注射)的肌红蛋白尿性急性肾衰竭大鼠;第四组:接受西咪替丁(150mg/kg腹腔注射)的肌红蛋白尿性急性肾衰竭大鼠;第五组:接受两种药物联合治疗的肌红蛋白尿性急性肾衰竭大鼠。注射甘油48小时后,测量收缩压。收集尿液和血液样本以评估尿量、肾小球滤过率、血尿素氮(BUN)、肌酐、钾、钠、血清肌酸激酶、一氧化氮和谷胱甘肽水平。取肾脏标本以研究肾细胞色素P450并进行组织学检查。与第二组相比,西咪替丁治疗显著降低了肌酐、BUN、钾、钠、收缩压和肌酸激酶,并增加了肾小球滤过率和尿量。左旋肉碱除了对钾和肾小球滤过率有影响外,也产生了类似的变化。与第二组相比,接受左旋肉碱或西咪替丁治疗的组中一氧化氮显著降低,而肾谷胱甘肽和细胞色素P450显著增加。与单独使用每种疗法相比,联合治疗进一步改善了肾功能、肌酸激酶、氧化应激参数和收缩压。组织学变化证实了生化结果。西咪替丁和左旋肉碱对肌红蛋白尿性急性肾衰竭具有几乎同等的保护作用。联合使用这两种药物可将肾损伤降至最低。

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