病灶区灌注噻唑烷二酮对家兔脑出血模型血肿周围脑组织过氧化酶活化增生受体γ及血脑屏障通透性的影响

项目名称： 病灶区灌注噻唑烷二酮对家兔脑出血模型血肿周围脑组织过氧化酶活化增生受体γ及血脑屏障通透性的影响

项目编号： No.81460185

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 伍国锋

作者单位： 贵州医科大学

项目金额： 45万元

中文摘要： 血肿周围继发性脑损伤是颅内出血的严重并发症，越来越多的实验证据表明氧化应激在颅内血肿所致的继发性脑组织损伤中发挥重要作用，而激活过氧化酶活化增生受体γ(PPARγ)可通过增加抗氧化剂和铜锌超氧化物歧化酶(SOD)的表达来降低氧化应激；我们前期的研究证明及时进行微创清除术能有效降低继发性脑组织损伤，因此，本研究拟观察PPARγ激动剂噻唑烷二酮结合微创颅内血肿清除术对病灶周围继发性脑损伤的治疗作用；选择健康家兔建立脑出血模型并分为不同观察组，采用立体定向微创技术清除颅内血肿，继而于血肿区内灌注噻唑烷二酮类药物进行干预，以病灶周围PPARγ表达、抗氧化剂过氧化氢酶、CD36、SOD、血脑屏障通透性、谷氨酸水平等为指标，观察病灶周围继发性脑损伤的变化；预期结果为微创颅内血肿清除术后给予噻唑烷二酮可明显减轻病灶周围继发性脑损伤程度，该项目的完成有望对病灶周围继发性脑损伤的治疗提供有效手段。

中文关键词： 脑血管病；脑出血；血脑屏障；过氧化酶活化增生受体γ；噻唑烷二酮

英文摘要： Intracerebral hemorrhage(ICH) often triggers a series of adverse events causing secondary brain insults and leads to severe neurological deficits. The increasing evidences indicate that oxidative stress plays a prominent role in the ICH-induced secondary brain damages.Activation of the peroxisome proliferator-activated receptor γ(PPARγ) might be reduce the the oxidative stress by inducing the expression of antioxidant catalase and copper/zinc superoxide dismutase (SOD).In our previous studies, we successfully established a model of intracerebral hematoma in rabbit, and optimized the time window for removing hematoma by minimally invasive procedure for evacuation, as well as studied the associated pathological injury.We hypothesize that activation of PPARγ combined with performing the minimally invaisive procedures for ICH evacation may significantly alleviate the pathological injury after intracerebral hematoma.The purposes of this study are to observe the preventive and therapeutic effects of PPARγ agonists Thiazolidinediones combined with the minimally invasive procedures for evacuation of intracerebral hematoma on the perihematomal secondary brain damages.Heathy rabbits are selected to establish the model of intracerebral hemorrhage by stereotactically infusing arterial blood into the animal`s basal ganglions.The rabbits are assigned to different groups for observation.The stereotactically minimally invasive surgery are used to evacuate the ICH followed by injection of Thiazolidinediones into the hematoma cavity.The perihematomal brain tissues are collected to determine the PPARγ,the CD36,the antioxidant catalase and SOD,the glutamate content,the blood-brain-barrier(BBB) permeability,as well as the brain water content(BWC).The neurofunction of the animal are also evaluated.The indexes mentioned above in the treatment group are compared with other groups.Performing the minimally invasive procedurs to evacuate the ICH followed by Thiazolidinediones might increase the level of PPARγ,the CD36,the expression of antioxidant catalase and SOD,simultaneously the perihematomal glutamate level,the BBB permeability as well as the BWC are decreased so that the secondary brain damages are reduced. Treatments with the agonists of PPARγ during/ after minimally invasive procedures may serve as a therapeutic strategy for intracerebral hematoma.

英文关键词： cerebrovascular disease;intracerebral hemorrhage;blood brain barrier;peroxisome proliferator-activated receptor-gamma;thiazolidinedione