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丙戊酸可预防L-NAME诱导的一氧化氮缺乏型高血压大鼠脂质代谢和肾脏肾素-血管紧张素系统的失调。

Valproic acid prevents the deregulation of lipid metabolism and renal renin-angiotensin system in L-NAME induced nitric oxide deficient hypertensive rats.

作者信息

Rajeshwari Thiyagarajan, Raja Boobalan, Manivannan Jeganathan, Silambarasan Thangarasu, Dhanalakshmi Thanikkodi

机构信息

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.

Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608 002, Tamil Nadu, India.

出版信息

Environ Toxicol Pharmacol. 2014 May;37(3):936-45. doi: 10.1016/j.etap.2014.02.008. Epub 2014 Mar 12.

Abstract

The present study was aimed to investigate the antihyperlipidemic and renoprotective potential of valproic acid against N(ω)-nitro-L arginine methyl ester hydrochloride (L-NAME) induced hypertension in male albino Wistar rats. In hypertensive rats, mean arterial pressure (MAP), kidney weight, levels of oxidative stress markers in tissues were increased. Dyslipidemia was also observed in hypertensive rats. Moreover, enzymatic and nonenzymatic antioxidant network also deregulated in tissues. Valproic acid (VPA) supplementation daily for four weeks brought back all the above parameters to near normal level and showed no toxicity which was established using serum hepatic marker enzyme activities and renal function markers. Moreover the up regulated expression of renin-angiotensin system (RAS) components were also attenuated by VPA treatment. All the above outcomes were confirmed by the histopathological examination. These results suggest that VPA has enough potential to attenuate hypertension, dyslipidemia and renal damage in nitric oxide deficiency induced hypertension.

摘要

本研究旨在探讨丙戊酸对N(ω)-硝基-L-精氨酸甲酯盐酸盐(L-NAME)诱导的雄性白化Wistar大鼠高血压的抗高血脂和肾脏保护作用。在高血压大鼠中,平均动脉压(MAP)、肾脏重量、组织中氧化应激标志物水平均升高。高血压大鼠中还观察到血脂异常。此外,组织中的酶促和非酶促抗氧化网络也失调。连续四周每日补充丙戊酸(VPA)使上述所有参数恢复到接近正常水平,且未显示出毒性,这是通过血清肝标志物酶活性和肾功能标志物确定的。此外,VPA治疗还减弱了肾素-血管紧张素系统(RAS)成分的上调表达。上述所有结果均经组织病理学检查证实。这些结果表明,VPA有足够的潜力减轻一氧化氮缺乏诱导的高血压中的高血压、血脂异常和肾脏损伤。

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