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丙戊酸钠对大鼠肾功能的影响。

Effects of sodium valproate on renal functions in rats.

作者信息

Hergüner M Ozlem, Altunbaşak Sakir, Doğan Ayşe, Yildizdaş Dinçer, Incecik Faruk, Erdoğan Seyda, Gönlüşen Gülfiliz, Dağlioğlu Kenan, Dikmen Nurten, Burgut Refik

机构信息

Department of Pediatric Neurology, Cukurova University, Faculty of Medicine, Adana, Turkey.

出版信息

Ren Fail. 2006;28(7):593-7. doi: 10.1080/08860220600843821.

Abstract

In recent years, it has been reported that sodium valproate occasionally can cause renal tubular impairment. This study was designed to demonstrate the renal tubular and glomerular functions in rats given sodium valproate as monotherapy, as well as to determine any reversibility of dysfunctions. Female rats were randomly allocated to three groups: group 1 received sodium valproate 500 mg/kg/d intraperitoneal for six weeks; after the same injection period, group 2 was housed for another six weeks, after which laboratory investigations were completed; and group 3 served as a control group made up of 20 healthy rats living in same condition without any treatment. Serum ALT, total protein, uric acid, ALP, phosphorus, sodium levels, and urine Ca/cr ratio were significantly different between groups 1 and 3 (p < 0.025), but this difference was not seen between groups 2 and 3. On the other hand, other parameters such as TRP, Ccr, NAG, and MDA were not significantly different among the three groups ( p > 0.025) These results suggest that SV does not have a significant dose- or time-related side effect on renal functions. Minor biochemical dysfunctions related to long-term sodium valproate therapy is reversible, and the minimal renal fibrosis that showed histopathologically is not clinically important. The renal tissues of rats are known to show similar metabolic and histological patterns with human renal tissues. No renal dysfunction was expected in humans because there were no clinically statistically significant renal side effects in this study.

摘要

近年来,有报道称丙戊酸钠偶尔会导致肾小管损伤。本研究旨在证明单独使用丙戊酸钠的大鼠的肾小管和肾小球功能,以及确定功能障碍的任何可逆性。将雌性大鼠随机分为三组:第1组腹腔注射丙戊酸钠500mg/kg/d,持续六周;在相同注射期后,第2组再饲养六周,之后完成实验室检查;第3组作为对照组,由20只生活在相同条件下未经任何处理的健康大鼠组成。第1组和第3组之间血清谷丙转氨酶、总蛋白、尿酸、碱性磷酸酶、磷、钠水平以及尿钙/肌酐比值存在显著差异(p<0.025),但第2组和第3组之间未观察到这种差异。另一方面,三组之间其他参数如肾小管磷重吸收率、内生肌酐清除率、N-乙酰-β-D-氨基葡萄糖苷酶和丙二醛没有显著差异(p>0.025)。这些结果表明丙戊酸钠对肾功能没有显著的剂量或时间相关副作用。与长期丙戊酸钠治疗相关的轻微生化功能障碍是可逆的,组织病理学显示的最小程度的肾纤维化在临床上并不重要。已知大鼠的肾组织与人类肾组织具有相似的代谢和组织学模式。由于本研究中没有临床统计学上显著的肾脏副作用,预计人类不会出现肾功能障碍。

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