Medhi Bikash, Aggarwal Raman, Chakrabarti Amitava
Indian J Exp Biol. 2010 Aug;48(8):793-9.
Present study was carried out to investigate the possible neuroprotective effect of pioglitazone, an antidiabetic agent, peroxisome proliferator-activated receptor gamma (PPARgamma) agonist on acute phase changes in mice model of cerebral ischemia induced by Bilateral Common Carotid artery Occlusion (BCCAO). BCCAO model was used to induce partial global cerebral ischemia. BCCAO induced significant brain infarct size and edema in saline treated control group along with high increase in oxidative stress showed by increase lipid peroxidation and decreased levels of antioxidants like superoxide superoxide dismutage, catalase, glutathione peroxidase. Pioglitazone (20 mg/kg, orally) administration showed neuroprotective effects by reducing cerebral infarct size significantly as compared to control group. Postischemic seizure susceptibility was also reduced as number of positive responders decreased to a significant number. Brain edema was subsided to a significant level. Pioglitazone reduced the plasma TNF-alpha levels as compared to ischemia group significantly. Pioglitazone treatment also improved all the antioxidants levels showing activity against oxidative stress induced by BCCAO. Pioglitazone showed neuroprotection against ischemic insult suggesting the role of PPARgamma agonist in neuroprotective agents.
本研究旨在探讨抗糖尿病药物、过氧化物酶体增殖物激活受体γ(PPARγ)激动剂吡格列酮对双侧颈总动脉闭塞(BCCAO)诱导的小鼠脑缺血模型急性期变化的可能神经保护作用。采用BCCAO模型诱导部分全脑缺血。在生理盐水处理的对照组中,BCCAO诱导了显著的脑梗死面积和脑水肿,同时氧化应激显著增加,表现为脂质过氧化增加以及超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶等抗氧化剂水平降低。与对照组相比,吡格列酮(20mg/kg,口服)给药通过显著减小脑梗死面积显示出神经保护作用。缺血后癫痫易感性也降低,因为阳性反应者的数量显著减少。脑水肿明显减轻。与缺血组相比,吡格列酮显著降低了血浆肿瘤坏死因子-α水平。吡格列酮治疗还提高了所有抗氧化剂水平,显示出对BCCAO诱导的氧化应激的活性。吡格列酮对缺血性损伤具有神经保护作用,提示PPARγ激动剂在神经保护剂中的作用。