Singh Amrit Pal, Singh Nirmal, Singh Bedi Preet Mohinder
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar, India.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, India.
J Surg Res. 2016 Jun 15;203(2):324-30. doi: 10.1016/j.jss.2016.02.038. Epub 2016 Mar 24.
Estrogen is reported to be renoprotective agent in various preclinical studies, attributing to its antioxidant and anti-inflammatory potential. The aim of present study was to investigate the involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ) in estrogen-mediated protection against renal ischemia reperfusion injury (IRI) in rats.
The renal damage induced by IRI (40-min ischemia and 24-h reperfusion) was assessed by measuring serum creatinine, creatinine clearance, blood urea nitrogen, serum uric acid, electrolytes, and microproteinuria in rats. The myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. Hematoxylin-eosin and periodic acid schiff staining of renal tissues were done to demonstrate histopathologic changes. Estrogen (0.2, 0.5, and 1.0 mg/kg, i.p.) was administered 1 h before subjecting rats to renal IRI. Separately, bisphenol A diglycyl ether (BADGE, 30 mg/kg, i.p.), a PPAR-γ receptor antagonist, was given before estrogen administration followed by IRI in rats.
The ischemia reperfusion demonstrated renal damage in rats with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. Estrogen administration demonstrated marked renoprotection that was attenuated by BADGE pretreatment in rats.
It is concluded that PPAR-γ agonism serves as one of the mechanisms in estrogen-mediated renoprotection.
在各种临床前研究中，雌激素被报道为一种肾脏保护剂，这归因于其抗氧化和抗炎潜力。本研究的目的是探讨过氧化物酶体增殖物激活受体γ（PPAR-γ）在雌激素介导的大鼠肾脏缺血再灌注损伤（IRI）保护中的作用。
通过测量大鼠血清肌酐、肌酐清除率、血尿素氮、血清尿酸、电解质和微量蛋白尿来评估IRI（40分钟缺血和24小时再灌注）诱导的肾脏损伤。测量髓过氧化物酶活性、硫代巴比妥酸反应物质、超氧阴离子生成和还原型谷胱甘肽水平，以评估肾组织中的氧化应激。对肾组织进行苏木精-伊红和过碘酸希夫染色，以显示组织病理学变化。在大鼠遭受肾脏IRI前1小时给予雌激素（0.2、0.5和1.0mg/kg，腹腔注射）。另外，在给予雌激素之前，先给大鼠腹腔注射双酚A二缩水甘油醚（BADGE，30mg/kg），一种PPAR-γ受体拮抗剂，随后进行IRI。
缺血再灌注显示大鼠出现肾脏损伤，血清和尿液参数有显著变化，氧化应激增强，肾组织出现组织病理学变化。给予雌激素显示出明显的肾脏保护作用，而在大鼠中BADGE预处理减弱了这种保护作用。
得出结论，PPAR-γ激动作用是雌激素介导的肾脏保护机制之一。
