Kaur Anudeep, Kaur Tajpreet, Singh Balbir, Pathak Devendra, Singh Buttar Harpal, Pal Singh Amrit
a Department of Pharmaceutical Sciences , Guru Nanak Dev University , Amritsar , Punjab , India.
b Department of Pharmacology, Khalsa College of Pharmacy , Amritsar , Punjab , India.
Ren Fail. 2016 Oct;38(9):1462-1467. doi: 10.1080/0886022X.2016.1214892. Epub 2016 Aug 3.
The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.
Rats were subjected to bilateral renal I/R (40 min I, 24 hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylin & eosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60 mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered prior to curcumin treatment in rats followed by AKI.
I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.
It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.
本研究探讨N-甲基-D-天冬氨酸（NMDA）受体在姜黄素介导的对大鼠缺血再灌注（I/R）诱导的急性肾损伤（AKI）的肾保护作用中的作用。
对大鼠进行双侧肾I/R（缺血40分钟，再灌注24小时）以诱导AKI。通过测量肌酐清除率、血尿素氮、血浆尿酸、钾水平、钠分数排泄和大量蛋白尿来评估肾损伤。通过测量髓过氧化物酶活性、硫代巴比妥酸反应性物质、超氧阴离子生成和还原型谷胱甘肽含量来评估肾组织中的氧化应激。进行苏木精和伊红染色以评估肾组织中的组织学变化。在大鼠发生AKI前1小时给予姜黄素（30和60mg/kg）。在不同组中，在大鼠接受AKI之前，先给予NMDA受体激动剂谷氨酸（200mg/kg）和亚精胺（20mg/kg），然后再给予姜黄素治疗。
I/R诱导的AKI表现为血浆和尿液参数的显著变化，以及肾组织中氧化应激的显著增加和组织学变化，而大鼠预先用谷氨酸和亚精胺处理会加重这些变化。给予姜黄素可显著预防AKI。然而，谷氨酸和亚精胺预处理可阻止姜黄素介导的肾保护作用。
得出结论，NMDA受体拮抗作用对姜黄素介导的对I/R诱导的AKI的保护作用有显著贡献。
